Treatment and prevention of lung cancer

Abstract

An immunogenic composition is described comprising a nucleic acid molecule encoding a plurality of antigens or cells presenting said plurality of antigens, wherein the antigens of said plurality of antigens are associated with mutations in at least two genes selected from TP53, KRAS and EGFR Related vectors, isolated nucleic acids and methods are described.

Description

[0001] TREATMENT AND PREVENTION OF LUNG CANCER

[0002] Field of the Present Disclosure

[0003] The present disclosure relates to immunogenic compositions, vectors for use in such immunogenic compositions, polynucleotides encoding such vectors, and methods of preventing cancer or cancer relapse in a patient using said compositions and products. The vectors and polynucleotides comprise one or more sequences that encode a plurality of antigens that are associated with genes that are recurrently mutated in lung cancer, including at least two of TP53, KRAS and EGFR.

[0004] Background

[0005] Lung cancer is the UK’s third most common cancer and is diagnosed in 48,500 people every year. It is also highly lethal, 18% of those diagnosed with lung cancer are alive at 5 years, the majority dying within 1 year of diagnosis. This corresponds to over 35,000 deaths from lung cancer every year in the UK. Histologically, around 80% lung cancer cases are non-small cell lung cancer (NSCLC) - encompassing adenocarcinoma, squamous cell and large cell histotypes. The strongest risk factors for NSCLC are smoking history (cigarettes, pipe or cigars) or chronic lung conditions such as COPD, emphysema, bronchitis, pneumonia and TB. It is therefore estimated that 79% NSCLC deaths could be prevented through smoking cessation interventions and earlier detection.

[0006] Low-dose CT (LDCT) screening has been employed to address this and has proved effective at reducing lung-cancer mortality in randomised trials (de Koning et al., 2020). LDCT screening is now being implemented across the UK in population subgroups at highest risk of lung cancer (i.e. current and former smokers) (Crosbie et al., 2019). While effective, only ~3% of screened individuals have confirmed lung cancer diagnoses at baseline scan (Crosbie et al., 2019) and hence 97% of participants remain at highly elevated lung cancer risk despite a negative scan. Indeed, data from the second round of screening (one year after baseline) shows up to 2.6% of participants who had a negative baseline scan develop lung cancer within only one year.

[0007] There remains an unmet need for methods and agents that can be used to reduce lung cancer mortality. The present invention addresses these and other needs, and provides related advantages as described herein.

[0008] Summary

[0009] The present inventors recognised that there was an unmet clinical need in the current clinical pipeline for lung cancer prevention, particularly in targeting high risk individuals for which regular screening is not sufficient. The present inventors recognised that if an approach could be developed to reduce the risk for these patients, this would be particularly beneficial as the patient group is readily identifiable and infrastructure / clinical pathways are already in place to recruit these high-risk individuals. In other words, the present inventors realised that there is an opportunity for a risk reducing intervention, as a primary prevention measure for lung cancer. The present inventors realised that a prophylactic vaccine could be an effective way to address this need.

[0010] The present inventors further postulated that a neoantigen-based approach could be effective in this context. Extensive functional and clinical validation of the potency of neoantigen targeting treatments has been demonstrated in cellular therapy (Tran et al. 2016) as well as recent positive therapeutic vaccination results in stage 111 / IV melanoma patients where, in a randomised design, risk of recurrence / death was reduced by 44% (see clinicaltrials.gov / study / NCT03897881). However, preventing the development of cancer or cancer recurrence is fundamentally different from treating cancer in that the approach cannot be personalised to the neoantigens present in an individual’s cancer. In other words, a prophylactic vaccine requires an “off-the-shelf’ nonpersonalised design. Priorto the inventor’s work, it was not clear whether such an approach would be viable as most neoantigens arise from private mutations found only in individual patients or small groups of patients, and all vaccine strategies have practical limits on how many neoantigens can be targeted, making it questionable whether a vaccine with sufficient patient coverage could be developed.

[0011] Surprisingly, the present inventors were able to identify a focused set of public neoantigens deriving from recurrent hotspot cancer driver gene mutations. To identify recurrent hotspot mutations, they conducted large-scale genomic analysis of n=61 ,813 cancer genomes (of which n=8,457 are lung cancer) and assessed the most frequent mutations in each cancer. The inventors identified the top 100 most frequent mutations, which they applied to a second independent dataset (MSK-GENIE study, n=114,827) to estimate the potential coverage of a given set of mutations (i.e. for a fixed cocktail of e.g. n=10 or n=20, etc, mutations, what percentage of patients’ tumours could be effectively targeted). This identified lung cancer as an attractive cancer for “off-the-shelf’ targeting, having a higher percentage coverage with fewer mutations compared to the mean coverage across all other tumour types. In the n=19,491 non-small cell lung cancer (NSCLC) cases studied, the inventors discovered that taking a cocktail of n=100 hotspot recurrent mutations, a maximum of 66.85% of patients’ lung cancers could be represented, and with n=20 mutations 48.37% are expected to be covered. When limiting to only lung adenocarcinomas (n=14,948), coverage could be further increased to a maximum of 71 .57% and a coverage of 54.28% for n=20 mutations.

[0012] The inventors further recognised that as well as hotspot mutations with high patient population frequency, it is further desirable for effective prophylactic vaccination to be likely to be present at the earliest phases of disease development. They therefore prioritised hotspot mutations in genes including TP53, KRAS and EGFR, that were identified as significantly mutated in pre-invasive forms of lung cancer as well as progressive disease (see e.g. Chen et al. 2019).

[0013] The inventors recognised that it is further advantageous for the epitopes included in such a vaccine to be immunogenic, and in particular, to be associated with evidence of epitope immunogenicity from T cell reactivity screening in patient samples. Using multiple T cell reactivity assays, the inventors prioritised those mutations which had demonstrated immunogenicity. Forthose prevalent mutations with no experimental evidence of immunogenicity, the inventors used bioinformatic methods to confirm predicted immunogenicity. Through this selection and filtering process, the inventors identified a set of 22 hotspot mutations. Finally, the inventors estimated the population coverage of the final cocktail of 22 hotspot mutations in two cohorts, which represent the proposed target population in a planned phase I clinical trial; Stage I lung adenocarcinomas from patients who are smokers or former smokers. These cohorts comprise a subset of the MSK-GENIE cohort (Biopharma Collaborative or BPC) which has richer clinical annotation (i.e. tumour stage and smoking status, n=1846) and the prospectively collected TRACERx 421 cohort (n=421). The inventors categorised a patient as “covered” by the vaccine if one or more mutations were present in the tumour, and the patient had a HLA allele proven to bind the mutation, as determined through experimental evidence or bioinformatic prediction. In these cohorts, the estimated coverage of the 22 hotspot cocktails were 58.9% and 55.2% in MSK-BPC and TRACERx 421 respectively. Thus, through the identification and extensive characterisation of a specific, extensively curated set of mutations, the vaccine designed is expected to cover over 50% of high-risk patients, potentially preventing the acquisition of lung cancer in a large number of patients.

[0014] The inclusion of tumour-associated antigens (TAAs) in addition to neoantigens, advantageously further provides protection for patients who do not have mutations in major cancer driver genes (Fig. 10A).

[0015] Accordingly, in a first aspect of the invention, there is provided an immunogenic composition comprising a nucleic acid molecule encoding a plurality of antigens or cells presenting said plurality of antigens, wherein the antigens of said plurality of antigens are associated with mutations in at least two genes selected from TP53, KRAS and EGFR.

[0016] Embodiments of the present aspect may have any one or more of the following optional features.

[0017] The cells presenting said plurality of antigens may be referred to as “antigen presenting cells”. The cells may be dendritic cells. The cells may be cells that have been pulsed with peptides corresponding to the plurality of antigens. Also described herein according to a further aspect is a vector comprising a nucleic acid molecule encoding a plurality of antigens that are associated with mutations in at least two genes selected from TP53, KRAS and EGFR. The vector may have any of the features described in relation to the first aspect.

[0018] In embodiments, the plurality of antigens comprise at least one antigen associated with a mutation in each of TP53, KRAS and EGFR. The plurality of antigens may comprise antigens associated with at least 5, at least 7, at least 9, at least 10, at least 11 , at least 18 antigens, between 5 and 30, between 10 and 30, between 15 and 25, or about 22 different mutations. In embodiments, each mutation is independently selected from an amino acid substitution, a single or multiple amino acid insertion or deletion, or delin. A mutation may be a coding mutation in an exon of the sequence coding for TP53, KRAS or EGFR.

[0019] In embodiments, the plurality of antigens are associated with mutations selected from: EGFR_T790M, EGFR_E746_A750del, EGFR_L861 Q, EGFR_L858R, KRAS_G13C, KRAS_G12V, KRAS_G12C, KRAS_G12A, KRAS_G12R, KRAS_G13D, KRAS_G12D,

[0020] TP53_R273L, TP53_G245C, TP53_R158L, TP53_V157F, TP53_R273H, TP53_R248Q,

[0021] TP53_R175H, TP53_R273C, TP53_R248W, TP53_Y234C, TP53_Y220C. Advantageously, these mutations are amongst the top 100 most prevalent mutations found in lung cancer patients, and have experimentally or bioinformatically validated ability to induce a T cell response. In embodiments, the plurality of antigens comprise mutations selected from: TP53_R175H, KRAS_G12V, KRAS_G12D, EGFR_L858R, TP53_Y220C, KRAS_G12C, EGFR_L858R, EGFR_T709V, TP53_G105V, EGFR_746_750del, EGFR_747_751del, EGFR_T790M, TP53_R248W, TP53_G245S, EGFR_E746_A750del, EGFR_H773L, EGFR_V774M, TP53_P152L, TP53_M237I. Advantageously, these mutations are amongst the top 100 most prevalent mutations found in lung cancer patients and have confirmed T cell reactivity in a plurality of patients and HLA types. In embodiments, the plurality of antigens comprise antigens associated with each of the following mutations: EGFR_T790M, EGFR_E746_A750del, EGFR_L861 Q, EGFR_L858R, KRAS_G13C, KRAS_G12V, KRAS_G12C, KRAS_G12A, KRAS_G12R, KRAS_G13D, KRAS_G12D, TP53_R273L, TP53_G245C, TP53_R158L, TP53_V157F, TP53_R273H, TP53_R248Q, TP53_R175H, TP53_R273C, TP53_R248W, TP53_Y234C, and TP53_Y220C.

[0022] In embodiments, the vector encoding one or more antigens that are experimentally verified or predicted to bind to MHC molecules encoded by multiple HLA alleles. Advantageously, this means the vaccine may be used to stimulate immunity in a larger number of subjects. In some embodiments, one or more of the plurality of antigens, or each antigen of the plurality of antigens, are capable of inducing a T cell reaction in subjects that have at least four different HLA types.

[0023] In embodiments, the plurality of antigens further comprise one or more tumour associated antigens, or immunogenic portions thereof, or wherein the cells further present one or more peptides from one or more tumour associated antigens. The one or more tumour-associated antigens may be selected from: MUC1 and NY-ESO-1. The nucleic acid molecule may further encodes NY-ESO-1 and / or an immunogenic portion of MUC1. Advantageously, by including one or more tumour-associated antigens (TAAs), the vaccine may be useful in providing protection against tumours that are negative for any of mutations within the antigens associated with mutations. In some embodiments, the vector or nucleic acid comprises a nucleotide sequence encoding the wild-type sequence of NY-ESO-1 and / or the wild-type sequence of MUC1 , or an immunogenic portion thereof, i.e. the nucleotide sequences do not comprise a mutation. In embodiments, the cells present one or more peptides obtained by processing polypeptides comprising the wild-type sequence of NY-ESO-1 (e.g. SEQ ID NO: 23) and / or the wild-type sequence of MUC1 (e.g. SEQ ID NO: 24), or an immunogenic portion thereof. In some embodiments, the nucleic acid encoding NY-ESO-1 or an immunogenic portion thereof has the sequence of SEQ ID NO.: 47. In some embodiments, the nucleic acid encoding NY-ESO-1 or an immunogenic portion thereof encodes the sequence of SEQ ID NO.: 23. In some embodiments, the nucleic acid encoding MUC1 or an immunogenic portion thereof has the sequence of SEQ ID NO.: 48. In some embodiments, the nucleic acid encoding MUC1 or an immunogenic portion thereof encodes the sequence of SEQ ID NO.: 24. In some embodiments, the vector may comprise multiple nucleotide sequences encoding different immunogenic portions of the same TAA.

[0024] In embodiments, the composition comprises a vector comprising a nucleic acid molecule encoding the plurality of antigens. The vector may be a DNA viral vector, optionally a ChAdOx vector, such as a ChAdOx2 vector. Advantageously, such vectors have a packaging capacity of around 2 kb, which means that the vector can express multiple different antigens. The vector may alternatively be a non-viral vector, such as a nanoparticle (e.g. a lipid (LNP), polymer-based, inorganic, hybrid nanoparticle or dendrimer). In embodiments, the vector is an mRNA nanoparticle. In embodiments, the vector is an mRNA lipid nanoparticle. In embodiments, the immunogenic composition comprises a nucleic acid and each antigen of the plurality of antigens associated with mutations comprises a sequence of 9 to 35 amino acids, optionally 25 amino acids in length, or wherein the immunogenic composition comprises antigen presenting cells that have been pulsed with the plurality of antigens, each antigen of the antigens associated with a mutation represented as a peptide of 9 to 35 amino acids, optionally 25 amino acids in length. In embodiments, each antigen of the plurality of antigens associated with mutations comprises a mutated residue or deletion in the centre of the peptide or the closest position to the centre of the peptide possible based on the position of the mutated residue or deletion in the protein. In embodiments, each antigen of the plurality of antigens associated with mutations comprises a sequence of 25 amino acids in length and the mutated reside is at position 8, 9, 10, 11 , 12, 13, 14, or 15, optionally wherein the mutated residue is at position 13 or the closest position to position 13 possible based on the position of the mutated residue in the protein. Advantageously, antigens of 25 amino acids in length may bind to MHC class II molecules as well as be processed into shorter peptides that bind to MHC class II molecules. In some embodiments, there may be approximately the same number of amino acids (e.g. 12 amino acids) either side of the mutated residue(s). In some embodiments, the mutated residue will be at approximately the same position in each antigen of the plurality of antigens associated with mutations. Advantageously, this increases the likelihood that each antigen can be processed into a plurality of peptides that comprise the mutation, increasing the likelihood that at least one of these peptides is strongly immunogenic, i.e. capable of inducing a T cell response. In some embodiments, the mutated residue is at position 13 in each of the antigens of the plurality of antigens associated with mutations.

[0025] In embodiments, the nucleic acid molecule comprises coding sequences for at least two antigens of the plurality of antigens that are concatenated, without separation by linker sequences. In embodiments, the nucleic acid comprises coding sequences for a plurality of antigens, including antigens associated with mutations and optionally tumour associated antigens or immunogenic portions thereof, immediately adjacent to each other.

[0026] In some embodiments, the plurality of antigens associated with mutations are expressed from a nucleic acid as a single polypeptide. In some embodiments, the plurality of antigens associated with mutations and the nucleotide sequence encoding NY-ESO-1 and / or MUC1 or immunogenic portions thereof are expressed as a single polypeptide. Such a polypeptide can be cleaved in a cell of a subject or in an antigen presenting cell comprised in the immunogenic composition to generate a plurality of peptides, at least some of which include mutated amino acid sequences (i.e. peptides derived from antigens as described herein), through normal antigen processing pathways. In embodiments, the nucleic acid molecule comprises concatenated coding sequences for all the antigens of the plurality of antigens, without separation by a linker sequence. In other words, all coding sequences for antigens associated with mutations and optionally tumour associated antigens (when used) may be immediately adjacent to each other in the vector. Advantageously, omitting linkers from the construct increases the number of antigen sequences that may be included in the vector before the packaging limit is reached. The nucleic acid may comprise coding sequences for the plurality of antigens, in an order such that the predicted number of epitopes comprising sequences from two adjacent antigens is the lowest possible given the antigens included in the vector.

[0027] In embodiments, the plurality of antigens that are associated with mutations, have amino acid sequences selected from: a. LGICLTSTVQLIMQLMPFGCLLDYV (SEQ ID NO.: 1); b. EGEKVKIPVAIKTSPKANKEILDEA (SEQ ID NO.: 2); c. QHVKITDFGLAKQLGAEEKEYHAEG (SEQ ID NO.: 3); d. KTPQHVKITDFGRAKLLGAEEKEYH (SEQ ID NO.: 4); e. MTEYKLWVGAGCVGKSALTIQLIQ (SEQ ID NO.: 5); f. MTEYKLWVGAVGVGKSALTIQLIQ (SEQ ID NO.: 6); g. MTEYKLWVGACGVGKSALTIQLIQ (SEQ ID NO.: 7); h. MTEYKLWVGAAGVGKSALTIQLIQ (SEQ ID NO.: 8); i. MTEYKLWVGARGVGKSALTIQLIQ (SEQ ID NO.: 9); j. MTEYKLWVGAGDVGKSALTIQLIQ (SEQ ID NO.: 10); k. MTEYKLWVGADGVGKSALTIQLIQ (SEQ ID NO.: 11); l. SGNLLGRNSFEVLVCACPGRDRRTE (SEQ ID NO.: 12); m. HYNYMCNSSCMGCMNRRPILTIITL (SEQ ID NO.: 13); n. WVDSTPPPGTRVLAMAIYKQSQHMT (SEQ ID NO.: 14); o. LWVDSTPPPGTRFRAMAIYKQSQHM (SEQ ID NO.: 15); p. SGNLLGRNSFEVHVCACPGRDRRTE (SEQ ID NO.: 16); q. YMCNSSCMGGMNQRPILTIITLEDS (SEQ ID NO.: 17); r. YKQSQHMTEWRHCPHHERCSDSDG (SEQ ID NO.: 18); s. SGNLLGRNSFEVCVCACPGRDRRTE (SEQ ID NO.: 19); t. YMCNSSCMGGMNWRPILTIITLEDS (SEQ ID NO.: 20); u. PPEVGSDCTTIHCNYMCNSSCMGGM (SEQ ID NO.: 21); and v. DRNTFRHSWVPCEPPEVGSDCTTI (SEQ ID NO.: 22).

[0028] In other words, the nucleic acid may comprise sequences encoding any of the above sequences. Further, the cells may present peptides derived from (e.g. by antigen processing) any of the above sequences, for example obtained by pulsing antigen presenting cells with peptides with any of the above sequences. In some embodiments, the nucleic acid comprises sequences encoding at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11 , at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 sequences selected from SEQ ID NOs.: 1 to 22. In some embodiments, the vector comprises sequences encoding all of SEQ ID NOs.: 1 to 22. In embodiments, the cells comprise cells presenting peptides derived from (e.g. by antigen processing) at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11 , at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 sequences selected from SEQ ID NOs.: 1 to 22. In embodiments, the cells comprise cells presenting peptides derived from (e.g. by antigen processing) all of SEQ ID NOs.: 1 to 22. In embodiments, the nucleic acid comprises a sequence encoding the following amino acid sequence(s) or the cells present one or more peptides derived from the following amino acid sequence(s): a. MQAEGRGTGGSTGDADGPGGPGIPDGPGGNAGGPGEAGATGGRGPRGAGAARASG PGGGAPRGPHGGAASGLNGCCRCGARGPESRLLEFYLAMPFATPMEAELARRSLAQD APPLPVPGVLLKEFTVSGNILTIRLTAADHRQLQLSISSCLQQLSLLMWITQCFLPVFLAQP PSGQRR (SEQ ID NO.: 23); and / or b. STAPPAHGVTSAPDTRPAPGSTAPP (SEQ ID NO.: 24).

[0029] In some embodiments, the nucleic acid comprises sequences encoding at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11 , at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 sequences selected from SEQ ID NOs.: 1 to 22, and at least one sequence selected from SEQ ID NOs.: 23 and 24. In some embodiments, the vector comprises sequence encoding SEQ ID NOs.: 1 to 22, and at least one sequence selected from SEQ ID NOs.: 23 and 24. In some embodiments, the vector comprises sequences encoding each of SEQ ID NOs.: 1 to 24. In embodiments, the cells comprise cells presenting peptides derived from (e.g. by antigen processing) at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11 , at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 sequences selected from SEQ ID NOs.: 1 to 22, and at least one sequence selected from SEQ ID NOs.: 23 and 24. In embodiments, the cells comprise cells presenting peptides derived from (e.g. by antigen processing) all of SEQ ID NOs: 1 to 24.

[0030] In embodiments, the nucleic acid comprises one or more nucleic acid sequences selected from: a. CTGGGCATCTGCCTCACCTCCACCGTGCAGCTCATCATGCAGCTCATGCCCTTCGG CTGCCTCCTGGACTATGTC (SEQ ID NO.: 25); b. GAAGGTGAGAAAGTTAAAATTCCCGTCGCTATCAAGACATCTCCGAAAGCCAACAAG GAAATCCTCGATGAAGCC (SEQ ID NO.: 26); c. CAGCATGTCAAGATCACAGATTTTGGGCTGGCCAAACAGCTGGGTGCGGAAGAGAA AGAATACCATGCAGAAGGA (SEQ ID NO.: 27); d. AAAACACCGCAGCATGTCAAGATCACAGATTTTGGGCGGGCCAAACTGCTGGGTGC GGAAGAGAAAGAATACCAT (SEQ ID NO.: 28); e. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTGGTTGCGTAGGCAAGAGTGCCTTG ACGATACAGCTAATTCAG (SEQ ID NO.: 29); f. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTGTTGGCGTAGGCAAGAGTGCCTTG ACGATACAGCTAATTCAG (SEQ ID NO.: 30); g. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTTGTGGCGTAGGCAAGAGTGCCTTG ACGATACAGCTAATTCAG (SEQ ID NO.: 31); h. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTGCTGGCGTAGGCAAGAGTGCCTTG ACGATACAGCTAATTCAG (SEQ ID NO.: 32); i. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTCGTGGCGTAGGCAAGAGTGCCTTG ACGATACAGCTAATTCAG (SEQ ID NO.: 33); j. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTGGTGACGTAGGCAAGAGTGCCTTG ACGATACAGCTAATTCAG (SEQ ID NO.: 34); k. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTGATGGCGTAGGCAAGAGTGCCTTG ACGATACAGCTAATTCAG (SEQ ID NO.: 35); l. AGTGGTAATCTACTGGGACGGAACAGCTTTGAGGTGCTTGTTTGTGCCTGTCCTGG GAGAGACCGGCGCACAGAG (SEQ ID NO.: 36); m. CACTACAACTACATGTGTAACAGTTCCTGCATGGGCTGCATGAACCGGAGGCCCATC CTCACCATCATCACACTG (SEQ ID NO.: 37); n. TGGGTTGATTCCACACCCCCGCCCGGCACCCGCGTCCTCGCCATGGCCATCTACAA GCAGTCACAGCACATGACG (SEQ ID NO.: 38); o. CTGTGGGTTGATTCCACACCCCCGCCCGGCACCCGCTTCCGCGCCATGGCCATCTA CAAGCAGTCACAGCACATG (SEQ ID NO.: 39); p. AGTGGTAATCTACTGGGACGGAACAGCTTTGAGGTGCATGTTTGTGCCTGTCCTGGG AGAGACCGGCGCACAGAG (SEQ ID NO.: 40); q. TACATGTGTAACAGTTCCTGCATGGGCGGCATGAACCAGAGGCCCATCCTCACCATC ATCACACTGGAAGACTCC (SEQ ID NO.: 41); r. TACAAGCAGTCACAGCACATGACGGAGGTTGTGAGGCACTGCCCCCACCATGAGCG CTGCTCAGATAGCGATGGT (SEQ ID NO.: 42); s. AGTGGTAATCTACTGGGACGGAACAGCTTTGAGGTGTGTGTTTGTGCCTGTCCTGG GAGAGACCGGCGCACAGAG (SEQ ID NO.: 43); t. TACATGTGTAACAGTTCCTGCATGGGCGGCATGAACTGGAGGCCCATCCTCACCATC ATCACACTGGAAGACTCC (SEQ ID NO.: 44); u. CCGCCTGAGGTTGGCTCTGACTGTACCACCATCCACTGCAACTACATGTGTAACAGT TCCTGCATGGGCGGCATG (SEQ ID NO.: 45); and v. GACAGAAACACTTTTCGACATAGTGTGGTGGTGCCCTGTGAGCCGCCTGAGGTTGG CTCTGACTGTACCACCATC (SEQ ID NO.: 46); or alternative versions thereof that encode the same amino acid sequences, optionally codon optimised versions thereof.

[0031] In some embodiments, the nucleic acid comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11 , at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 sequences selected from SEQ ID NOs.: 25 to 46. In some embodiments, the nucleic acid comprises SEQ ID NOs.: 25 to 46.

[0032] In embodiments, the immunogenic composition comprises the sequence of: a. ATGCAGGCCGAAGGCCGGGGCACAGGGGGTTCGACGGGCGATGCTGATGGCCCA GGAGGCCCTGGCATTCCTGATGGCCCAGGGGGCAATGCTGGCGGCCCAGGAGAG GCGGGTGCCACGGGCGGCAGAGGTCCCCGGGGCGCAGGGGCAGCAAGGGCCTC GGGGCCGGGAGGAGGCGCCCCGCGGGGTCCGCATGGCGGCGCGGCTTCAGGGC TGAATGGATGCTGCAGATGCGGGGCCAGGGGGCCGGAGAGCCGCCTGCTTGAGTT CTACCTCGCCATGCCTTTCGCGACACCCATGGAAGCAGAGCTGGCCCGCAGGAGC CTGGCCCAGGATGCCCCACCGCTTCCCGTGCCAGGGGTGCTTCTGAAGGAGTTCA CTGTGTCCGGCAACATACTGACTATCCGACTGACTGCTGCAGACCACCGCCAACTG CAGCTCTCCATCAGCTCCTGTCTCCAGCAGCTTTCCCTGTTGATGTGGATCACGCAG TGCTTTCTGCCCGTGTTTTTGGCTCAGCCTCCCTCAGGGCAGAGGCGC (SEQ ID NO.: 47); and / or b. TCCACCGCCCCCCCAGCCCACGGTGTCACCTCGGCCCCGGACACCAGGCCGGCC CCGGGCTCCACCGCCCCCCCA (SEQ ID NO.: 48), or alternative versions thereof that encode the same amino acid sequences, optionally codon optimised versions thereof.

[0033] In some embodiments, the vector comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11 , at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, or at least 21 sequences selected from SEQ ID NOs.: 25 to 46, and at least one sequence selected from SEQ ID NOs.: 47 and 48. In some embodiments, the vector comprises SEQ ID NOs.: 25 to 46, and at least one sequence selected from SEQ ID NOs.: 47 and 48. In some embodiments, the vector comprises SEQ ID NOs.: 25 to 48. In embodiments, the nucleic acid comprises a nucleic acid sequence selected from: SEQ ID NO.: 93, 92, 82, 86, 49, 51 , 61 , 63, 84, 94, SEQ ID NO.: 52, 54, 64, 66, SEQ ID NO.: 51 , 66 and SEQ ID NO.: 52, 68. In some embodiments, the vector comprises a nucleic acid sequence encoding an amino acid sequence selected from SEQ ID NOs.: 93, 92, 82, 86, 50, 53, 56, 59, 62, 65, 68, and 71. In embodiments, the nucleic acid comprises a nucleic acid sequence selected from: SEQ ID NO: 93, 92, 82, 86.

[0034] In embodiments, the nucleic acid comprises a sequence that encodes a molecular adjuvant or the composition comprises a molecular adjuvant. In embodiments, the nucleic acid comprises a sequence that encodes a fusion of a molecular adjuvant and the plurality of antigens or the composition comprises a fusion of a molecular adjuvant and the plurality of antigens. In embodiments, the molecular adjuvant is a peptide comprising a human CD74 invariant chain transmembrane domain.

[0035] Also described herein is a nucleic acid molecule or set of nucleic acid molecules encoding a plurality of antigens that are associated with mutations in at least two genes selected from TP53, KRAS and EGFR. The nucleic acid molecule(s) may be mRNAs. The nucleic acid molecules may have any of the features described in relation to any embodiment of the first aspect.

[0036] Also described according to a further aspect is an isolated nucleic acid molecule or molecules comprising a sequence encoding a vector comprising a nucleic acid molecule encoding a plurality of antigens that are associated with mutations in at least two genes selected from TP53, KRAS and EGFR. The vector may have the features of any embodiment of the first aspect.

[0037] Also described according to a further aspect is an isolated host cell comprising a vector comprising a nucleic acid molecule encoding a plurality of antigens that are associated with mutations in at least two genes selected from TP53, KRAS and EGFR. The vector may have the features of any embodiment of the first aspect.

[0038] Also described according to a further aspect is an isolated nucleic acid molecule or set of nucleic acid molecules encoding a plurality of antigens that are associated with mutations in at least two genes selected from TP53, KRAS and EGFR. The vector may have any of the features of any embodiment of the first aspect.

[0039] Also described according to a further aspect is a method of preventing cancer or cancer recurrence in a subject, comprising administering to the subject an effective amount of an immunogenic composition, vector or nucleic acid molecule according to any preceding aspect. An effective amount may be a therapeutically effective amount. An effective amount may be an amount sufficient to reduce the risk of recurrent / new primary lung cancer in a subject who has been treated with the immunogenic composition compared to a control subject. In embodiments, the methods described herein may reduce the risk of recurrent / new primary lung cancer in a subject who has been treated with the immunogenic composition compared to a control subject by at least 35% over 5 years.

[0040] Also described herein is an immunogenic composition, a vector or a nucleic acid molecule according to any preceding aspect, for use in a method of preventing lung cancer or lung cancer recurrence in a subject.

[0041] Also described herein is an immunogenic composition, a vector, a host cell or a nucleic acid molecule according to any preceding aspect, for use in the manufacture of a medicament. The medicament may be a medicament for the prevention of lung cancer or lung cancer recurrence in a subject.

[0042] In any embodiment of a method of treatment, therapeutic use or manufacture of a medicament, the cancer may be lung adenocarcinoma. The subject may be a subject who has been diagnosed as being at risk of developing lung cancer. The subject may be a subject who has been diagnosed as having lung adenocarcinoma in situ (AIS). The subject may be a subject who has been diagnosed as having minimally invasive adenocarcinoma (MIA). The subject may be a subject who has been diagnosed as having stage 1 a or 1 b lung cancer that has been resected. The subject may be a subject who is in remission from lung cancer. The subject may be a subject who does not have lung cancer that is detectable by low-dose CT scanning.

[0043] The subject may be a subject who has a history of smoking and / or a chronic lung condition. The subject may be a subject who has been diagnosed as having one or more indeterminate pulmonary nodules. Such subjects may be considered as likely to develop lung cancer. The chronic lung condition may be selected from: chronic obstructive pulmonary disease (COPD), emphysema, bronchitis, pneumonia and tuberculosis.

[0044] A vector, composition or nucleic acid of the disclosure may be administered intramuscularly. A vector, composition or nucleic acid may be administered as a plurality of doses, for example between 2 and 4 doses. In embodiments, a plurality of doses comprise a first dose, and a second dose administered between 4 and 16 weeks (e.g. about 4 weeks, about 28 days, about 1 month, about 12 weeks, about 3 months) after administration of a first dose. In embodiments, a plurality of doses further comprise a third dose administered between about 6 months and about 12 months after administration of the first dose, e.g. about 12 months after administration of the first dose. In embodiments, a plurality of doses further comprise a fourth dose administered between about 12 months and about 24 months after administration of the first dose, e.g. about 18 months after administration of the first dose. In embodiments, administration of the vector, composition or nucleic acid is associated with a reduction in the risk of recurrence or new primary lung cancer in a subject, an increase in overall survival, an increase in cancer free survival, a reduction or maintenance of size and / or number of indeterminate pulmonary nodules in a subject at a predetermined period of time after administration of the vector, composition or nucleic acid (e.g. the first administration of the vector, composition or nucleic acid).

[0045] Reference to preventing cancer recurrence encompass any therapeutic use in a patient that has been previously diagnosed as having cancer and as being in at least partial remission from the cancer.

[0046] Brief Description of Figures

[0047] Fig. 1 shows a line graph showing concentration curve analysis based on the MSK-GENIE cohort. Concentration curve data for NSCLC (n= 19,491), lung adenocarcinoma (n= 14,948) and all other cancer types (n= 114,827). Plotted on the x-axis are hotspot mutations, with the most frequent on the left first and then in descending order towards lower frequencies. On the y-axis is the % of patients in each cancer type, that are covered by each set number of mutations. The “All other” group is based on the average across the individual concentration curves for all cancer types outside of NSCLC. GENIE 13.1 release is used as the largest available data source (see gdc.cancer.gov / about-gdc / contributed-genomic-data-cancer-research / genie).

[0048] Fig. 2 shows a table showing hotspot mutations with confirmed T cell reactivity in two or more independent patients, split by HLA type. Experimental T cell reactivity was determined through ELISPOT, IFN ELISA, Killing assay, Cytometric Bead Array or fluorescent automatic cell sorting (FACS). Numbers represent unique assay counts. Data was obtained from NEPdb: A Database of T-Cell Experimentally-Validated Neoantigens and Pan-Cancer Predicted Neoepitopes for Cancer Immunotherapy and via manual extraction from the following studies, Malekzadeh et al., 2019, Bear et al., 2021 , Tran et al., 2016, Yossef et al., 2018, Wang et al., 2016, Ito et al., 2007, Gjertsen et al., 1997, Veatch et al., 2019, Li et al., 2021 , Wu et al., 2020 and Ding et al., 2021 .

[0049] Fig. 3 shows a workflow schematic showing the process for determining the final vaccine targets. A database was compiled containing peptides derived from known mutations with proven ability to elicit T cell reactivity, including data extracted from NEPdb and data extracted manually from published literature. This database was then narrowed down by restricting to mutations with proven T cell reactivity (either experimentally or bioinformatically), and then restricting to those mutations found within 3 driver genes that are mutated early in the development of lung cancer: KRAS, EGFR, and TP53. A final cocktail of 22 highly prevalent hotspot mutations across the three genes was identified, comprising 12 mutations with one or more experimentally proven reactivities and 10 with bioinformatically predicted reactivity. Two prevalent tumour-associated antigens (TAAs) were selected to provide coverage for those patients who do not have one of the 22 hotspot mutations. Fig. 4 shows a step line plot showing estimated coverage of final hotspot cocktail in different clinical subgroups. The percentages coverage of hotspot mutations were estimated in two cohorts with in- depth clinical data on smoking status and tumour stage. Fig. 4A shows clinical data on smoking status and tumour stage firstly in a subset of the MSK-GENIE cohort known as the Biopharma Collaborative (BPC) n=1 ,846. Fig. 4B shows clinical data on smoking status and tumour stage in the TRACERx 421 cohort, n=421. Coverage was estimated in all smokers within the cohorts and in smokers with early stage (stage 1) disease. On the y-axis is the percentage of patients that are covered by each set number of mutations within the cocktail of 22 hotspots. The dashed line displays the maximum coverage which can be achieved using all 22 hotspot mutations.

[0050] Fig. 5 shows a step line plot showing concentration curve analysis based on the TCGA LUAD cohort. Plotted on the x-axis are hotspot mutations, with the most frequent on the left first and then in descending order towards lower frequencies. Included with the hotspots is the expression of both TAAs NY-ESO-1 (CTAG1 B) and MUC1 whereby a patient is considered as expressing the TAA if their expression value is above the bottom quartile for the cohort. On the y-axis is the % of patients in each cancer type, that are covered by each set number of mutations plus TAAs.

[0051] Fig. 6 shows a min-max bar chart showing the estimated percentage patient coverage achieved for a vaccine when up to 22 randomly selected peptides containing the hotspot mutations of Table 3 are included in the vaccine.

[0052] Fig. 7 shows a schematic showing the workflow for determination of T cell reactivity to hotspot neoantigen vaccine epitopes. The illustrated workflow for immunoreactivity assays shows fluorospot screening pipeline in the upper panel, and MANAFEST (Danilova et al., 2018) screening pipeline in lower panel.

[0053] Fig. 8 shows graphs and well images illustrating T cell reactivity to hotspot neoantigen vaccine epitopes: EGFR mutations. Fig. 8A shows a line graph showing fold increase in the number of specific CDR3 beta chain sequences detected for EGFR and viral (CMV, EBV, Flu [CEF]) peptides via MANAFEST. PBMCs were sampled over three timepoints shown (months, x-axis), and fold calculated relative to the first timepoint pre-vaccination (month 30). Representative images from Fluorospot recall assay testing all vaccine peptides in PBMCs from 40 months (post vaccine). Fig. 8B shows a bar chart showing the proportion of the repertoire in each sample that is occupied by significantly expanded CDR3s (shown as bar segments) reactive to EGFR.T790M (top panel) EFGR.746_750del (ex19del or INDEL) (middle panel) and CEF (bottom panel) peptides as determined by MANAFEST. Connecting waves indicate clonotype sharing between samples, all CDR3s significantly expanded at any timepoint are shown. CEF=CMV, EBV, Flu viral pools of peptides. Fig. 8C shows example images of wells from fluorospot assay. Fig. 8D shows a bar chart showing quantification ofGZMB release by fluorospot, bars represent the mean + / -SEM of triplicate cultures *q<0.05, 2-way AN OVA corrected for multiple testing via Benjamini Hochberg. This data provides evidence that vaccination in vivo in humans using these epitopes can generate a T cell response. This is much stronger evidence of clinical applicability than exogenously stimulating immune cells removed from the circulation (as in e.g. an ELISPOT assay). Fig. 9 shows a set of four plasmid maps showing the initial ChAdOx vectors used in Examples of the disclosure. Fig. 9A shows a plasmid map of pC1789 pChAdOx2-LungVax_V2. Fig. 9B shows a plasmid map of pC1788 pChAdOx2-LungVax_V1 , Fig. 9C shows a plasmid map of pC1790 pChAdOx2-LungVax_V3. Fig. 9D shows a plasmid map of pC1791 pChAdOx2-LungVax_V4. Fig. 9E shows a plasmid map of pC1901 pChAdOx2-LungVax_V2_new. Fig. 9F shows a plasmid map of pC1902 pChAdOx2-LungVax_liV2_new.

[0054] Fig. 10 illustrates the identification of early-stage lung cancer antigens persisting in advanced stages. Fig. 10A illustrates the process used to design a vaccine according to examples of the disclosure. Fig. 10B shows patient coverage for mutations in KRAS, EGFR, and TP53. Each node represents cumulative coverage by the addition of mutations in the following order: KRAS (G12C, G12V, G12D, G12A, G13C, G13D, G12R), EGFR (L858R, E746_A750del, EGFR_T790M, E746_A750del variant 2, EGFR_L861Q), TP53 (R158L, R273L, V157F, R175H, R273C, R248Q, R248W, Y220C, G245C, R273H, Y234C). Similar patterns are seen in other cohorts (TCGA, PCAWG, TRACERx); analysed here is the largest MSKCC-GENIE cohort. Fig. 10C shows percentage of patients with each mutation included in the LungVax vaccine. Fig. 10D shows that incorporating tumour-associated antigens (TAAs) NY-ESO-1 (CTAG1 B) and MUC1 , along with 22 hotspot mutations, increased LungVax vaccine coverage to 89.93%. This analysis was based on the TCGA Lung Adenocarcinoma dataset, comprising 566 patients.

[0055] Fig. 11 shows expression of ChAdOx2 inserts in lung and immune cells. Fig. 11A shows a schematic of the ChAdOx2 vector constructs V1-V4, V2i (“V2li”) and V4i (“V4li”). Fig. 11 B and C show Western blots showing expression of LungVax inserts in the MRC-05 normal lung fibroblasts cell line and the A549 lung adenocarcinoma cell line, 48 hours after infection with ChAdOx2- LungVax vectors (V1-V4 lanes 2-5, no insert negative control lane 6), using anti-V5-tag and anti- L858R EGFR antibodies, p-actin is included as a loading control. ChAdOx2-GFP is included as a positive control (lane 7), and no vector as a negative control (lane 1). The V5-tag is incorporated into the insert for detection purposes (preclinical version only), while L858R EGFR represents a hotspot mutation integrated into the LungVax inserts. The V5 band (green) corresponds to the same molecular weight as the L858R EGFR band (red) when detected using LICOR anti-mouse (V5) and anti-rabbit (L858R EGFR) antibodies, resulting in a merged yellow colour. Fig. 11 B shows results in MRC-05 lung cell line. Fig. 11C shows results in the A549 lung adenocarcinoma cell line.

[0056] Fig. 12 shows GFP expression after ChAdOx2 transfection in a variety of cell lines. Fig. 12A shows fluorescence images of DC2.4 C57BL / 6 murine dendritic cells, RAW 264.7 murine BALB / C monocytes, and primary human PBMCs after exposure to the ChAdOx2-GFP vector. Microscopic analysis demonstrates their ability to express GFP (green-marked cells) following infection. Fig. 12B shows expression of GFP in CD3-CD8- monocyte derived dendritic cells (MoDCs) measured by flow cytometry after 16-hour co-culture with Jurkat cells (CD3+CD8+). Co-cultures were initiated 2 days post initial infection of MoDC with multiplicity of infection (MOI) of 10 for all viral conditions. Conditions include infection with ChAdOx2-GFP (“GFPVax”), ChAdOx2-LungVax_V2 (“V2”), ChAdOx2-LungVax_V4 (“V4”), ChAdOx2-LungVax_V2i (“V2Li”), ChAdOx2-LungVax_V4i (“V4Li”), All 25Mer, and Jurkat cells alone (“T alone”) and non-infected MoDCs + Jurkat cells (“unloaded DC”) controls. All 25mer is a masterpool of long peptides which include all those found in the vaccine with sequences as shown in Table 3 (SEQ ID NO: 1-24).

[0057] Fig. 13 shows a schematic showing the overall configuration of the four initial LungVax inserts, V1- V4, and RT-qPCR primers designed for detecting the mRNA expression of antigens in the LungVax vaccine. Sequence annotations include the EGFR_L858R 25mer, NYESO1 , the 22 selected LungVax hotspot mutations, the MUC1 TAA, and the V5 tag. To detect LungVax vaccine insert expression at the mRNA level, RT-qPCR primers were designed to target specific antigens in the LungVax vaccine. The primers were designed to avoid amplifying endogenous mRNA. For example, the forward primer anneals to L858R cDNA, while the reverse primer anneals to NYESO- 1 cDNA. Other primers target HotSpot antigen cDNA with the reverse primer annealing to V5 cDNA.

[0058] Fig. 14 shows a bar graph showing mRNA expression of the LungVax insert, detected by RT-qPCR in A549 cells transduced with LungVax vaccines for 48 hours at MO110. Expression is represented as -AACt, with actin as the normalization reference gene. A549 cells transduced with the ChAdOx2 GFP vector serve as the control, while the LungVax V1-V4 ChAdOx2 vectors are experimental samples. MUC1 expression is detected in cells expressing V2 and V4 (which contain MUC1) but not in V1 and V3 (which lack MUCI). L858R EGFR and NYESO-1 primers detect mRNA in V1 and V2 (which contain NYESO-1), while no expression is detected in V3 and V4 (which lack NYESO- 1). This is further confirmed by primers targeting NYESO-1 cDNA. The black bar detects mRNA expression of the insert with the L858R sequence at the end (V3 and V4), as expected. The data confirms expression of the LungVax antigens in these cells. Expression was also confirmed in MRC-05 cells. The primer sets for RT-qPCR analysis of vaccine insert antigen expression are shown in Table 10, with names showing amplified products corresponding to bar graph expression levels in Fig. 14.

[0059] Fig. 15 shows box and whisker plots representing LungVax peptide binding to BALB / c mouse MHO I molecules (H-2Dd and H-2Kd). Peptide number corresponds to those shown in Fig.16. Stability of antigen presentation is assessed using a BFA decay assay, measuring a half-life in hours. Fig. 15A shows box and whisker plots representing LungVax peptide binding to BALB / c mouse MHC I molecule H-2Dd. Fig. 15B shows box and whisker plots representing LungVax peptide binding to BALB / c mouse MHC I molecule H-2Kd.

[0060] Fig. 16 shows a schematic illustration of the LungVax peptide pool, shown located against the full LungVax insert V2. The arrows indicate an unbroken contiguous sequence continuing from the top to the bottom half.

[0061] Fig. 17 shows a schematic illustrating the BALB / c mice vaccination, sampling, and analysis workflow for a short term in vivo immunogenicity assay used in examples of the disclosure. IU - international unit. Fig. 18 shows set of scatterplots illustrating an example workflow of FACS sorting and gating of BALB / c PBMCs. The example shown is for LungVax V1 ; the same workflow was applied to each construct tested.

[0062] Fig. 19 shows results demonstrating that V1 , V2 and V2i vaccines elicit strong CD8+ T cell IFNy and TN Fa responses. The vector variants are illustrated on Fig. 11 A. Fig. 19A shows Western blots demonstrating expression of LungVax inserts in A549 lung adenocarcinoma cell line, 48 hours after infection with ChAdOx2-LungVax vectors (no insert control, V1-V4, V2i and V4i), using anti- L858R EGFR antibody. Fig. 19B-E show a summary of immunogenic response in BALB / c mice. Fig. 19B shows IFNy CD8+ T cell secretion 14 days after prime vaccination. Fig. 19C shows TNFa CD8+ T cell secretion 14 days after prime vaccination. Fig. 19D shows IFNy CD8+ T cell secretion 7 days after booster vaccination. Fig. 19E shows TNFa secretion 7 days after booster vaccination. Responses were measured after stimulation with the ChAdOx2-LungVax peptide pool, using the indicated LungVax vaccines. The V2i vaccine variant elicits the strongest CD8+ T cell IFNy and TNFa responses among all the vaccine variants.

[0063] Fig. 20 shows a table showing the specificity of CD8+ T splenocytes from V2i-vaccinated mice 10 days after a second booster. Fig. 20A shows results for individual 25mer peptides spanning hotspot mutations from the LungVax insert co-cultured with splenocytes for 5 hr. Immunogenic responses, measured by the percentage of CD8+ and IFN-y+ cells, were assessed. Responses are categorised as follows: - for 0-1%, + for 1-2%,++ for 2-3%, +++ >3% and ++++ for >10% CD8+ & IFN-y+ cells. The 25mers are simply the full length of each hotspot antigen included in the vaccine, with sequences as provided in Table 3 (SEQ ID NO: 1-24). Fig. 20B shows results for a shorter peptide of R248Q TP53 which was used in the assay when negative responses to 25-mer peptide were observed, resulting in enhanced reactions. NT indicates peptides not yet tested. The data averages two replicates. The 25-mer peptides with negative immunogenicity responses are more hydrophobic, challenging to generate, and prone to aggregation. Shorter peptides covering these immunogenic regions will be tested. The data show that 10 days post last booster, CD8+ T cells from V2i-vaccinated mice react to individual LungVax 25mer antigens.

[0064] Fig. 21 shows three bar charts representing the activation of specific T-cell receptors in response to LungVax-infected MoDCs. TCR-knockout Jurkat (left panel) mock transfected or reconstituted with TCR recognising NYESO R9M:HLA-A*0201 (middle) or p53R175H:HLA-A*0201 (right) were exposed to treated moDC for 16hr at a 1 :5 DOT ratio. Readout for activation was % in CD69 positive gate (i.e. percentage of CD69 expression on Jurkat cells). All jurkat conditions were cocultured for 16 hours with moDCs infected with lungvax versions: V2, V4, V2Li, V4Li; or peptide pulsed moDCs for all lungvax long peptides (All 25Mer - as indicated above, this is a masterpool of long peptides - 25mers- which cover the full length of each hotspot region found in the vaccine, the sequence of these is shown in Table 3). The data show activation of TP53 R175H and NY- ESO-1 specific T-Cell receptors in response to LungVax-infected MoDCs (monocyte-derived dendritic cells).

[0065] Fig. 22 shows that V2 and V2i vaccines elicit long-term CD8+ T cell IFN-y responses in PBMCs 90 days post-last boost. Fig. 22A shows a schematic illustrating the BALB / c mice vaccination, sampling, and analysis workflow for the long term in vivo immunogenicity assay. Ill - international unit. Fig. 22B shows the percentage of CD8+ cells secreting IFNy after stimulation with the LungVax peptide pool, measured in PBMCs from BALB / c mice 50 and 90 days post-second booster vaccination with the indicated vaccines. Responses are presented as the average of 3 replicates. Fig. 22C shows the percentage of CD8+ cells secreting TNFa after stimulation with the LungVax peptide pool, measured in PBMCs from BALB / c mice 50 and 90 days post-second booster vaccination with the indicated vaccines. Responses are presented as the average of 3 replicates.

[0066] Fig. 23 shows a pair of dot plots illustrating that the V2i Design 2 vaccine (lacking V5 Tag, including L861Q EGFR antigen) elicits strong CD8+ T Cell IFNy and TNFa responses. The immunogenic responses of PBS and V2i Design 2 vaccinated BALB / c mice to the total LungVax peptide pool are shown. Fig. 23A shows responses quantified by the percentage CD8+ IFN-y+ cells. Fig. 23B shows responses quantified by the percentage of CD8+ TNF-a+ cells in PBMCs. Both are measured 14 days after the prime vaccination and 7 days after the booster vaccination, as indicated in the figure. The LungVax peptide pool includes all the peptides shown along the x-axis of Fig. 25A.

[0067] Fig. 24 shows a schematic representing the antigens and their positions within the V2i Design 2 (V2i D2) LungVax vaccine insert, color-coded by the proteins they encode: yellow for NY-ESO-1 , blue for EGFR, green forTP53, red for KRAS, and bright green for MUC1 .

[0068] Fig. 25 shows two graphs presenting results from an in vivo immunogenicity assay in BALB / c mice (experimental set up on Fig. 17). Fig. 25A shows a bar chart of immunogenicity to individual peptides (peptides shown in Fig.16, with sequences provided in Table 9), measured by the percentage of CD8+ T cells releasing IFN-y in splenocytes 14 days after the booster dose. Amino acid numbering indicates the position of each peptide within the V2i Design 2 vaccine insert. ‘Multiple’ indicates peptides corresponding to multiple regions within the V2i sequence. Multiple 1 maps to TP53_G245C aa 234-243 and TP53_Y234C aa 495-504. Multiple 2 maps to TP53_G245C aa 248-257, TP53_R248Waa 320-329, TP53_R248Q aa 570-579. Multiple 3 maps to KRAS G13D aa 397-406; G12A aa 422-431 ; G12C aa 447-456; G12V aa 472-481 ; G13C aa 522-531 ; G12R aa 697-706; and G12D aa 722-731 . Fig. 25B shows a dot plot of the binding of LungVax peptides to BALB / c MHC-I molecules H-2Dd and H-2Kd, assessed using a BFA-decay assay in RMAS-Dd and RMAS-Kd cells. Peptides (x-axis) exhibited measurable half-lives for binding to either H-2Dd or H-2Kd. No peptides bound H-2Ld. For peptides binding both H-2Dd and H-2Kd, only the stronger interaction (longer half-life) is shown. Colour coding follows that Fig. 24. Kd27 and TV9 are positive controls for H-2Kd MHC class I - Kd27 is derived from is derived from the protein ovalbumin (OVA) while TV9 is derived from a testis antigen.

[0069] Fig. 26 is a set of heatmaps indicating epitope binding predictions between LungVax insert positions (x-axis) and HLA alleles (y-axis). Fig 26A shows predictions for HLA-A. Fig. 26B shows predictions for HLA-B. Fig. 26C shows predictions for HLA-C. POEM score is calculated by the POEM hybrid intelligence model (a neural network trained to predict class I epitope immunogenicity). Darker colour indicates a higher POEM score. Epitopes shown are subject to a high threshold; top 0.01 % of predicted epitopes and those with a POEM score greater than or equal to the median score seen for known immunogenic peptides in a training dataset. Additionally, only mutation-containing hotspot peptides comprised in the LungVax insert are shown, in addition to TAA derived peptides. All mutation-containing hotspot peptides of lengths 8 to 14 amino acids were considered from the LungVax V2i sequence. The position on the x-axis is the position within the V2i primary structure covered by the peptide (i.e. 144 to 151 would be an 8mer).

[0070] Detailed Description

[0071] The specific embodiments described herein are offered byway of example, not by way of limitation. Any sub-titles herein are included for convenience only, and are not to be construed as limiting the disclosure in any way. The features disclosed in the foregoing description, or in the following claims, or in the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for obtaining the disclosed results, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof. Any section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0072] Throughout this specification, including the claims which follow, unless the context requires otherwise, the word “comprise” and “include”, and variations such as “comprises”, “comprising”, and “including” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about,” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value is optional and means for example + / - 10%. In describing the present invention, the following terms will be employed, and are intended to be defined as indicated below.

[0073] Neoantigens

[0074] The present disclosure relates at least in part to antigens associated with coding mutations in one or more cancer driver genes. The mutations are hotspot mutations. A “mutation” refers to a difference in a nucleotide sequence (e.g. DNA or RNA) in a tumour cell compared to a healthy cell from the same individual. The difference in the nucleotide sequence can result in the expression of a protein which is not expressed by a healthy cell from the same individual. For example, the mutation may be a single nucleotide variant (SNV, a sequence change where, compared to a reference sequence, one nucleotide is replaced by one other nucleotide), multiple nucleotide variants (MNV, a sequence change where, compared to a reference sequence, a plurality of contiguous nucleotides is replaced by the same number of different contiguous nucleotides), a deletion mutation (a sequence change where, compared to a reference sequence, one or more nucleotides are not present (deleted)), an insertion mutation (a sequence change where, compared to the reference sequence, one or more nucleotides are inserted and where the insertion is not a copy of a sequence immediately 5'), a delin mutation (a sequence change where, compared to a reference sequence, one or more nucleotides are replaced by one or more other nucleotides and which is not a substitution, inversion or conversion), or an inversion (a sequence change where, compared to a reference sequence, more than one nucleotide replacing the original sequence are the reverse complement of the original sequence). Any such mutation may result in a substitution in the encoded amino acid sequence (missense mutation), insertion in the encoded amino acid sequence (in frame insertion or delin), deletion in the encoded amino acid sequence (in frame deletion or delin), frameshift (insertion, deletion ordelin not in frame), in the truncation of the amino acid sequence (early termination) or in differently spliced sequence (splice site mutation). Thus, the mutations used herein are mutations resulting in a change in the amino acid sequence (coding mutation) that is expressed, compared to a reference sequence that does not include the mutation. A hotspot mutation is a mutation at a position that is frequently mutated in a plurality of subjects with cancer. The present disclosure relates in particular to mutations at positions that are hotspots in lung cancer.

[0075] The present disclosure relates in particular to mutations that give rise to neoantigens. A neoantigen is an antigen that arises as a consequence of a mutation within a cancer cell. A neoantigen is therefore not expressed in healthy (i.e. non-tumour) cells. Antigens (including neoantigens) are presented to immune cells by MHC proteins encoded by HLAgenes. The human leukocyte antigen (HLA) system is a gene complex encoding the major histocompatibility complex (MHC) proteins in humans. A neoantigen may be processed to generate distinct peptides which can be recognised by T cells when presented in the context of MHC molecules. A neoantigen presented as such may represent a target for therapeutic or prophylactic intervention in the treatment or prevention of cancer in a subject. The HLA locus is extremely polymorphic, resulting in a plurality of MHC alleles that each have a specific profile of binding to peptides. Binding of an antigen to MHC molecules is a necessary (although not sufficient) condition for T cell recognition and activation.

[0076] The present disclosure relates in particular to mutations in the EGFR, KRAS and TP53 genes.

[0077] “EGFR” as used herein refers to epidermal growth factor receptor encoded by the gene EGFR. The UniProt accession number for the human EGFR protein is P00533. The amino acid sequence of human EGFR is shown at UniProt P00533-1 , dated 1997-11-01 v2. The GenelD for the human EGFR gene is 1956. Antigens comprising peptides associated with coding mutations in EGFR are described. Coding mutations in EGFR as described herein include EGFR_T790M, EGFR_E746_A750del, EGFR_L861 Q, EGFR_L858R, EGFR_G719A, EGFR_S768I, EGFR_L747_T751del, EGFR_E709_T710delinsD. In embodiments, coding mutations in EGFR are selected from EGFR_T790M, EGFR_E746_A750del, EGFR_L861Q, and EGFR_L858R. EGFR_T790M refers to a mutation at position 790 of the human EGFR sequence, or a corresponding position in a homologous sequence, in which the amino acid at position 790 is M (instead of T in the wild type sequence). The notation also refers to a peptide comprising a portion of the sequence of EGFR including said mutation at said position. EGFR_E746_A750del refers to a deletion of amino acids at positions 746 to 750 of the human EGFR sequence or corresponding positions in a homologous sequence. The notation also refers to a peptide comprising at least a portion of the sequence of EGFR including one or more amino acids preceding position 746 immediately adjacent to one or more amino acids subsequent to position 750 (or corresponding positions in a homologous sequence). In other words, EGFR_E746_A750del can refer to a peptide comprising at least a portion of the sequence of EGFR including at least positions 745-751 and in which positions 746-750 (which are ELREA in the wild type sequence) are deleted. EGFR_L861Q refers to a mutation at position 861 of the human EGFR sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is Q (instead of L in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of EGFR including position 861 of the human sequence (which is a L in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 861 is Q. EGFR_L858R refers to a mutation at position 858 of the human EGFR sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position (instead of L in the wild type sequence). The notation also refers to peptide comprising at least a portion of the sequence of EGFR including position 858 of the human sequence (which is a L in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 858 is R. EGFR_G719A refers to a mutation at position 719 of the human EGFR sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is A (instead of in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of EGFR including position 719 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 719 is A. EGFR_S768I refers to a mutation at position 768 of the human EGFR sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is I (instead of S in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of EGFR including position 768 of the human sequence (which is a S in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 768 is I. EGFR_L747_T751 del refers to a deletion of amino acids at positions 747 to 751 of the human EGFR sequence or corresponding positions in a homologous sequence. The notation also refers to a peptide comprising at least a portion of the sequence of EGFR including one or more amino acids preceding position 747 immediately adjacent to one or more amino acids subsequent to position 751 (or corresponding positions in a homologous sequence). In other words, EGFR_L747_T751del can refer to a peptide comprising at least a portion of the sequence of EGFR including at least positions 746-752 and in which positions 747-751 are deleted. EGFR_E709_T710delinsD refers to a replacement of amino acids 709-710 (which are ET in the wild type sequence) of the human EGFR sequence or corresponding positions in a homologous sequence and insertion of a D at the deletion site. In other words, EGFR_E709_T710delinsD can refer to a peptide comprising at least a portion of the sequence of EGFR including at least positions 709-710 and in which positions 709-710 are deleted and replaced by D.

[0078] Thus, the term “mutation in a EGFR gene” refers to any mutation that result in the presence of an amino acid in the encoded protein that is not present in the protein encoded by the normal sequence, where the mutations can be selected from mutations that cause the presence of: at position 790: M, at positions 746-750:deletion, at position 861 : Q, at position 858: R, at position 719: A, at position 768: I, at positions 747-751 : deletion, and at positions 709-710: insertiondeletion. In embodiments, the mutations are selected from mutations that cause the presence of: at position 790: M, at positions 746-750: deletion, at position 861 : Q, at position 858: R. Antigens associated with said mutations may refer to peptides encoded by a portion of the coding sequence of EGFR including said mutations. Thus, antigens associated with mutations in EGFR may refer to peptides that comprise a portion of the amino acid sequence of EGFR, said portions including at positions corresponding to the following positions in the EGFR sequence: at position 790: M, at positions 746-750:deletion, at position 861 : Q, at position 858: R, at position 719: A, at position 768: 1, at positions 747-751 : deletion, and at positions 709-710: insertion-deletion. In embodiments, antigens associated with mutations in EGFR may refer to peptides that comprise a portion of the amino acid sequence of EGFR, said portions including at positions corresponding to the following positions in the EGFR sequence: at position 790: M, at positions 746-750: deletion, at position 861 : Q, and at position 858: R.

[0079] “KRAS” as used herein refers to GTPase Kras encoded by the gene KRAS. The UniProt accession number for the human KRAS protein is P01116. The amino acid sequence of human KRAS is shown at UniProt P01116-1 , dated 1986-07-21 v1. The GenelD for the human EGFR gene is 3845. Antigens comprising peptides associated with coding mutations in KRAS are described. Coding mutations in KRAS as described herein include KRAS_G13C, KRAS_G12V, KRAS_G12C, KRAS_G12A, KRAS_G12R, KRAS_G13D, KRAS_G12D, KRAS_Q61 L, KRAS_Q61 H, and KRAS_G12S. In embodiments, coding mutations in KRAS are selected from KRAS_G13C, KRAS_G12V, KRAS_G12C, KRAS_G12A, KRAS_G12R, KRAS_G13D, and KRAS_G12D. KRAS_G13C refers to a peptide comprising at least a portion of the sequence of KRAS including position 13 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 13 is C. KRAS_G12V refers to a mutation at position 12 of the human KRAS sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is V (instead of G in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of KRAS including position 12 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 12 is V. KRAS_G12C refers to a mutation at position 12 of the human KRAS sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is C (instead of G in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of KRAS including position 12 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 12 is C. KRAS_G12A refers to a mutation at position 12 of the human KRAS sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is A (instead of G in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of KRAS including position 12 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 12 is A. KRAS_G12R refers to a mutation at position 12 of the human KRAS sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is R (instead of G in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of KRAS including position 12 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 12 is R. KRAS_G13D refers to a mutation at position 13 of the human KRAS sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is D (instead of G in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of KRAS including position 12 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 12 is D. KRAS_G12D refers to a mutation at position 12 of the human KRAS sequence ora corresponding position in a homologous sequence, wherein the amino acid at said position is D (instead of G in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of KRAS including position 12 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 12 is D. KRAS_Q61 L refers to a mutation at position 61 of the human KRAS sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is L (instead of Q in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of KRAS including position 61 of the human sequence (which is a Q in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 61 is L. KRAS_Q61 H refers to a mutation at position 61 of the human KRAS sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is H (instead of Q in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of KRAS including position 61 of the human sequence (which is a Q in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 61 is H. KRAS_G12S refers to a mutation at position 12 of the human KRAS sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is S (instead of G in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of KRAS including position 12 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 12 is S.

[0080] Thus, the term “mutation in a KRAS gene” refers to any mutation that result in the presence of an amino acid in the encoded protein that is not present in the protein encoded by the normal sequence, where the mutations can be selected from mutations that cause the presence of: at position 13: C or D, at position 12: V, A, R, D, or S, at position 61 : L or H. In embodiments, the mutations are selected from mutations that cause the presence of: at position 13: C or D, at position 12: V, A, R, or D. Antigens associated with said mutations may refer to peptides encoded by a portion of the coding sequence of KRAS including said mutations. Thus, antigens associated with mutations in KRAS may refer to peptides that comprise a portion of the amino acid sequence of KRAS, said portions including at positions corresponding to the following positions in the KRAS sequence: at position 13: C or D, at position 12: V, A, R, S or D, at position 61 : L or H. In embodiments, antigens associated with mutations in KRAS may refer to peptides that comprise a portion of the amino acid sequence of KRAS, said portions including at positions corresponding to the following positions in the KRAS sequence: at position 13: C or D, at position 12: V, A, R or D.

[0081] “TP53” as used herein refers to cell tumour antigen p53 encoded by the gene TP53. The UniProt accession number for the human TP53 protein is P04637. The amino acid sequence of human TP53 is shown at UniProt P04637-1 , dated 2009-11-24 v4. The GenelD for the human TP53 gene is 7157. Antigens comprising peptides associated with coding mutations in TP53 are described. Coding mutations in TP53 as described herein include TP53_R273L, TP53_G245C, TP53_R158L, TP53_V157F, TP53_R273H, TP53_R248Q, TP53_R175H, TP53_R273C, TP53_R248W, TP53_Y234C, TP53_Y220C, TP53_S215I, TP53_H193R, TP53_A159V, TP53_C141Y,

[0082] TP53_L194R, TP53_E285K, TP53_M237I, TP53_R249S, TP53_C242F, TP53_C176F,

[0083] TP53_R249M, TP53_G266V, TP53_A159P, TP53_R110L, TP53_H179Y, TP53_R337L,

[0084] TP53_R248L, TP53_G245V, TP53_G154V, TP53_H214R, TP53_R282W, TP53_Y163C, and TP53_H179R. In embodiments, coding mutations in TP53 are selected from TP53_R273L, TP53_G245C, TP53_R158L, TP53_V157F, TP53_R273H, TP53_R248Q, TP53_R175H, TP53_R273C, TP53_R248W, TP53_Y234C, and TP53_Y220C. TP53_R273L refers to a peptide comprising at least a portion of the sequence of TP53 including position 273 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 273 is L.TP53_G245C refers to a mutation at position 245 of the human TP53 sequence ora corresponding position in a homologous sequence, wherein the amino acid at said position is C (instead of G in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 245 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 245 is C.TP53_R158L refers to a mutation at position 158 of the human TP53 sequence ora corresponding position in a homologous sequence, wherein the amino acid at said position is L (instead of R in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 158 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 158 Is L.TP53_V157F refers to a mutation at position 157 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is F (instead of V in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 157 of the human sequence (which is a V in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 157 is F. TP53_R273H refers to a mutation at position 273 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is H (instead of R in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 273 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 273 Is H. TP53_R248Q refers to a mutation at position 248 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is Q (instead of R in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 248 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 248 Is Q. TP53_R175H refers to a mutation at position 175 of the human TP53 sequence ora corresponding position in a homologous sequence, wherein the amino acid at said position is H (instead of R in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 175 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 175 Is H.TP53_R273C refers to a mutation at position 273 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is C (instead of R in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 273 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 273 is C.TP53_R248W refers to a mutation at position 248 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is W (instead of R in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 248 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 248 is W. TP53_Y234C refers to a mutation at position 234 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is C (instead of Y in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 234 of the human sequence (which is a Y in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 234 is C. TP53_Y220C refers to a mutation at position 220 of the human TP53 sequence ora corresponding position in a homologous sequence, wherein the amino acid at said position is C (instead of Y in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 220 of the human sequence (which is a Y in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 220 is C.

[0085] TP53_S215I refers to a mutation at position 215 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is I (instead of S in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 215 of the human sequence (which is a S in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 215 Is I. TP53_H193R refers to a mutation at position 193 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is R (instead of H in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 193 of the human sequence (which is a H in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 193 Is R. TP53_A159V refers to a mutation at position 159 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is V (instead of A in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 159 of the human sequence (which is a A in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 159 Is V. TP53_C141Y refers to a mutation at position 141 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is Y (instead of C in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 141 of the human sequence (which is a C in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 141 Is Y. TP53_L194R refers to a mutation at position 194 of the human TP53 sequence ora corresponding position in a homologous sequence, wherein the amino acid at said position is R (instead of L in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 194 of the human sequence (which is a L in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 194 Is R. TP53_E285K refers to a mutation at position 285 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is K (instead of E in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 285 of the human sequence (which is a E in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 285 Is K. TP53_M237I refers to a mutation at position 237 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is I (instead of M in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 237 of the human sequence (which is a M in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 237 Is I. TP53_R249S refers to a mutation at position 249 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is S (instead of R in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 249 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 249 Is S. TP53_C242F refers to a mutation at position 242 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is F (instead of C in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 242 of the human sequence (which is a C in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 242 Is F. TP53_C176F refers to a mutation at position 176 of the human TP53 sequence ora corresponding position in a homologous sequence, wherein the amino acid at said position is F (instead of C in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 176 of the human sequence (which is a C in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 176 Is F. TP53_R249M refers to a mutation at position 249 of the human TP53 sequence ora corresponding position in a homologous sequence, wherein the amino acid at said position is M (instead of R in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 249 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 249 Is M. TP53_G266V refers to a mutation at position 266 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is V (instead of G in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 266 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 266 Is V. TP53_A159P refers to a mutation at position 159 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is P (instead of A in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 159 of the human sequence (which is a A in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 159 Is P. TP53_R110L refers to a mutation at position 110 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is L (instead of R in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 110 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 110 Is L. TP53_H179Y refers to a mutation at position 179 of the human TP53 sequence ora corresponding position in a homologous sequence, wherein the amino acid at said position is Y (instead of H in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 179 of the human sequence (which is a H in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 179 Is Y. TP53_R337L refers to a mutation at position 337 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is L (instead of R in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 337 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 337 Is L. TP53_R248L refers to a mutation at position 248 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is L (instead of R in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 248 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 248 Is L. TP53_G245V refers to a mutation at position 245 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is V (instead of G in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 245 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 245 Is V. TP53_G154V refers to a mutation at position 154 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is V (instead of G in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 154 of the human sequence (which is a G in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 154 Is V. TP53_H214R refers to a mutation at position 214 of the human TP53 sequence ora corresponding position in a homologous sequence, wherein the amino acid at said position is R (instead of H in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 214 of the human sequence (which is a H in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 214 Is R. TP53_R282W refers to a mutation at position 282 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is W (instead of R in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 282 of the human sequence (which is a R in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 282 Is W. TP53_Y163C refers to a mutation at position 163 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is C (instead of Y in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 163 of the human sequence (which is a Y in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 163 Is C. TP53_H179R refers to a mutation at position 179 of the human TP53 sequence or a corresponding position in a homologous sequence, wherein the amino acid at said position is R (instead of H in the wild type sequence). The notation also refers to a peptide comprising at least a portion of the sequence of TP53 including position 179 of the human sequence (which is a RH in the wild type sequence) or a corresponding position in a homologous sequence, in which the amino acid at position 179 Is R.

[0086] Thus, the term “mutation in a TP53 gene” refers to any mutation that result in the presence of an amino acid in the encoded protein that is not present in the protein encoded by the normal sequence, where the mutations can be selected from mutations that cause the presence of: at position 273: L, H or C, at position 245: C, at position 158: L, at position 157: F, at position 248: Q or W, at position 175:1-1, at position 234: C, at position 215:1, at position 193:R, at position 159:V, at position 141 :Y, at position 194:R, at position 285:K, at position 237:l, at position 249:S, at position 242:F, at position 176:F, at position 249:M, at position 266:V, at position 159:P, at position 110:L, at position 179:Y, at position 337:L, at position 248:L, at position 245:V, at position 154:V, at position 214:R, at position 282:W, at position 163:C, and at position 179:R. In embodiments, the mutations are selected from mutations that cause the presence of: at position 273: L, H or C, at position 245: C, at position 158: L, at position 157: F, at position 248: Q or W, at position 175:H, at position 234: C. Antigens associated with said mutations may refer to peptides encoded by a portion of the coding sequence of TP53 including said mutations. Thus, antigens associated with mutations in TP53 may refer to peptides that comprise a portion of the amino acid sequence of TP53, said portions including at positions corresponding to the following positions in the TP53 sequence: at position 273: L, H or C, at position 245: C, at position 158: L, at position 157: F, at position 248: Q or W, at position 175:H, at position 234: C, at position 215:1, at position 193:R, at position 159:V, at position 141 :Y, at position 194:R, at position 285:K, at position 237:l, at position 249:S, at position 242:F, at position 176:F, at position 249:M, at position 266:V, at position 159:P, at position 110:L, at position 179:Y, at position 337:L, at position 248:L, at position 245:V, at position 154:V, at position 214:R, at position 282:W, at position 163:C, and at position 179:R. In embodiments, antigens associated with mutations in TP53 may refer to peptides that comprise a portion of the amino acid sequence of TP53, said portions including at positions corresponding to the following positions in the TP53 sequence: at position 273: L, H or C, at position 245: C, at position 158: L, at position 157: F, at position 248: Q or W, at position 175:H, at position 234: C.

[0087] The sequences associated with each of the above Uniprot and GenelD entries are incorporated herein by reference in their entirety.

[0088] Vectors in accordance with the present disclosure comprise nucleic acid sequences that encode neoantigens. Such nucleic acid sequences may be referred to as “neoantigen sequences”. The neoantigen sequences may comprise a mutation referred to herein as a “hotspot mutation”. A “hotspot mutation” is a mutation is a mutation that is recurrent in a cohort of subjects. A hotspot mutation may be defined by applying a threshold on prevalence in a cohort of patient. For example, a mutation may be considered to be a hotspot mutation if it is present in at least a predetermined percentage of patients in the cohort, and / or if it is present in the cohort with a prevalence that is amongst the top x observed prevalence in the cohort (where x can be e.g. 20, 50 or 100). The cohort of subjects may be a cohort of lung cancer patients. For example, a hotspot mutation may be a mutation that is amongst the top 100 most prevalent point mutations found in all the lung cancer studies available in cBioportal as of 10 / 12 / 2022; n = 8,457 lung cancer patients. The neoantigen sequences may comprise a mutation in a gene that is frequently mutated in pre- invasive forms of lung cancer, in particular adenocarcinoma in situ (AIS) of the lung, and / or minimally invasive adenocarcinoma (MIA). Such mutations may be referred to as “driver mutations”. In particular, the neoantigen sequences may comprise sequences encoding mutated forms of TP53, KRAS and / or EGFR. Thus, the term “hotspot mutation” may be used to refer to any of the mutations in TP53, KRAS and EGFR mentioned above. Mutations in each of these genes were identified as frequent in early stages of cancer. Advantageously, by immunising against such mutations, an immune response can be initiated against the cancer cells at an earlier stage of development, where there are fewer cancerous cells and / or the cells are less invasive. For example, the vectors and compositions of the present disclosure may be useful for preventing adenocarcinoma in situ (AIS) of the lung, and / or minimally invasive adenocarcinoma (MIA). The antigen sequences of the plurality of antigen sequences associated with mutations may comprise mutations that are prevalent in AIS and / or MIA. Such mutations may be identified by selective analysis of cohorts of patients with AIS and / or MIA. The antigen sequences of the plurality of antigen sequences associated with mutations may comprise mutations that are established driver mutations, that drive the progression of AIS and / or MIA to invasive disease, such as non-small cell lung cancer (NSCLC).

[0089] Tumour-associated Antigens

[0090] Vectors according to the present disclosure may comprise one or more tumour-associated antigen (TAA). A “tumour-associated antigen (TAA)” is a protein or peptide that does not include mutated amino acids but that is more highly expressed in cancer cells compared to normal cells, and that is antigenic (i.e. capable of triggering an immune response in a subject, also referred to as immunogenic). A tumour-associated antigen may be selected from: NY-ESO-1 , MUC1 or antigenic portions thereof.

[0091] “NY-ESO-1” as used herein refers to cancer / testis antigen 1 , also known as Autoimmunogenic cancer / testis antigen NY-ESO-1 , LAGE2 or LAGE2B, encoded by the gene CTAG1B. The terms “NY-ESO-1” and “CTAG1 B” are used herein interchangeably to refer to the tumour associated antigen encoded by the CTAG1B gene. The UniProt accession number for the human NY-ESO-1 protein is P78358. The amino acid sequence of human NY-ESO-1 is shown at UniProt P78358-1 , dated 1997-05-01 vl . The GenelDs for the human CTAG1A gene are 1485 and 246100. A vector according to the disclosure may comprise a sequence encoding all or part of NY-ESO-1 . The vector may comprise the full coding sequence of NY-ESO-1 (SEQ ID NO.: 23).

[0092] “MUC1” as used herein refers to Mucin-1 , encoded by the gene MUC1. The UniProt accession number for the human MUC1 protein is P15941. The amino acid sequence of human MUC1 is shown at UniProt P15941-1 , dated 2010-05-18 v3. The GenelD for the human MLIC1 gene is 4582. A vector according to the disclosure may comprise a sequence encoding all of part of MUC1 . The vector may comprise an immunogenic portion of MUC1 having the sequence of SEQ ID NO.: 24. The vector may comprise other immunogenic portions of MUC1 , such as those described in Table 1 of Kovjazin et al. (2014), i.e.: amino acids 1-21 of MUC1 (SP domain), amino acids 10-21 of MUC1 (SP domain) (optionally as a 17-mer where the MUC1 sequence is flanked by 2K upstream and 3K downstream), amino acids 13-21 of MUC1 (SP domain), amino acids 12-20 of MUC1 (SP domain), amino acids 10-13 of MUC1 (SP domain), amino acids 5-13 of MUC1 (SP domain), amino acids 7-15 of MUC1 (SP domain), amino acids 130-154 of MUC1 (TRA domain).

[0093] In embodiments, one or more additional known TAAs (see e.g. Safi et al. 2017) may be included in the vector, such as e.g. HER2 / neu, Aurora Kinase A, CEA, MAGE-A3, etc. The use of MUC1 is believed to be advantageous based on prior clinical trial results (not shown). The use of NY-ESO- 1 is believed to be advantageous as T cells specific to this antigen have been identified in NSCLC patients and their presence has been associated with improved prognosis (Safi et al. 2017).

[0094] The sequences associated with each of the above Uniprot and GenelD entries are incorporated herein by reference in their entirety.

[0095] Vectors & Compositions

[0096] The present disclosure also relates to pharmaceutical compositions, and in particular immunogenic compositions, comprising a vector according to the disclosure, a nucleic acid encoding antigens according to the disclosure, or a population of antigen presenting cells displaying antigens according to the disclosure (i.e. neoantigens and optionally tumour associated antigens). An immunogenic composition is a composition that is capable of inducing an immune response to an antigen present in the composition or expressed in a subject upon administering the composition. The immune response is preferably a cellular immune response, such as a polyfunctional T cell immune response. Thus, the immunogenic composition may be able to stimulate cellular immunity. The vectors, nucleic acids and cell populations of the disclosure can be formulated as pharmaceutical compositions for clinical use and may comprise a pharmaceutically acceptable carrier, diluent, excipient or adjuvant. In accordance with the present disclosure methods are also provided for the production of pharmaceutically useful compositions. In embodiments, methods of production according to the disclosure comprise one or more steps selected from: obtaining an isolated nucleic acid comprising a sequence encoding a vector as described herein; producing a vector as described herein; obtaining one or more host cells comprising a vector as described herein; and / or mixing a vector as described herein with a pharmaceutically acceptable carrier, adjuvant, excipient or diluent. In other embodiments, methods of production according to the disclosure comprise one or more steps selected from: obtaining a population of antigen presenting cells in cell culture, and pulsing the population of antigen presenting cells with a plurality of antigen peptides as described herein and / or introducing nucleic acid encoding for a plurality of antigens as described herein into the cells (e.g. by electroporating mRNA encoding said antigens into the cells). Obtaining a population of antigen presenting cells in cell culture may comprising culturing a previously obtained sample of cells. Thus, the methods may be entirely performed in vitro. An antigen presenting cell may be a dendritic cell, such as a monocyte derived dendritic cell or a leukemia-derived dendritic cell. The antigen presenting cells may be autologous to a subject to which the composition is to be administered. In yet other embodiments, methods of production according to the disclosure comprise one or more steps selected from: obtaining a vector as described herein comprising sequences encoding a plurality of antigens as described herein (e.g. a plasmid)), in vitro transcribing a plurality of mRNA molecules each encoding an antigen as described herein from the obtained vector, and formulating the mRNA molecules for delivery for example by forming a polyplex, lipid nanoparticle or viral vector.

[0097] Any type of vector suitable for delivery of coding sequences into mammalian cells may be used in accordance with the present invention. For example, the nucleic acid may be DNA and the vector may be a viral vector. Alternatively, the nucleic acid may be mRNA and the vector may be a viral vector, polyplex or lipid nanoparticle vector. The vector may be a DNA based vector. The vector may be a viral vector. DNA based viral vectors advantageously enable the delivery of multiple antigens using a single vector, which is capable of generating a cellular immune response. Preferably, the packaging limit of the viral vector may be about 2 kb. The vector may be genetically modified to express a plurality of peptides comprising antigenic sequences selected from the neoantigens and TAAs described herein. A vector is used to introduce components in a cell, which are encoded in an insert sequence that is inserted into the vector. The insert includes coding sequences for a plurality of immunogenic peptides as described herein. The vector may have a packaging limit sufficient to receive an insert of up to about 2kb. Such a vector size is sufficient to include coding sequences for up to 22 neoantigens as described herein (see e.g. coding sequences in Tables 1 and 2) and one or more TAA coding sequences including e.g. the full NY- ESO-1 sequence and a MUC1 peptide (see e.g. sequences of SEQ ID NO: 23 and 24). Examples of insert sequences are provided in SEQ ID NO.: 49, 51 , 52, 54, 55, 57, 58, 60, 61 , 63, 64, 66, 67, 69, 70, 72, 82, 84, 86, 92, 93 and 94. Examples of insert sequences include any insert sequence that encodes a polypeptide comprising the sequence of any of SEQ ID Nos: 50, 53, 56, 59, 62, 65, 68, 71 , 83, 85, and 87. If the packaging limit is less than 2 kb, the vector may comprise coding sequences for a subset of the neoantigens described herein (e.g. a subset of the peptides in Table 1 and / or in Table 2) and one, both or no TAA sequences. For example, the insert may be selected from: SEQ ID NO.: 49, 51 , 52, 54, 55, 57, 58, 60, 61 , 63, 64, 66, 67, 69, 70, 72, 82, 84, 86, 92, 93 and 94. The insert may comprise coding sequence for peptides encoding any one or more of the hotspot mutations identified in Table 1 and 2, provided that at least one mutation in at least two of KRAS, EGFR and TP53, or in each of KRAS, EGFR and TP53 is represented. The insert may comprise coding sequence for peptides encoding a plurality of the hotspot mutations identified in Table 1 , the plurality of mutations including at least one mutation in at least two of KRAS, EGFR and TP53, or in each of KRAS, EGFR and TP53.

[0098] The vector may be an adenoviral vector. The vector may be a Chimpanzee Adenovirus vector (ChAd). “Chimpanzee Adenovirus vector (ChAd)” as used herein is a replication-deficient adenovirus strain derived from non-human primates that evades pre-existing immunity in humans, genetically modified to include in its genome foreign DNA (insert, i.e. DNA that does not naturally belong to adenoviruses). In particular, the ChAd vector may be genetically modified to express one or more peptides comprising neoantigens according to the present disclosure. Thus, the ChAd vector may refer to viral particles of ChAd that comprise the ChAd genome, and coding sequences for antigenic peptides as described herein introduced in the ChAd genome. A heterologous prime-boost vaccination approach, consisting of a non-replicating chimpanzee adenovirus (ChAd) prime vector followed by an MVA boost has been used as a therapeutic and prophylactic for many infectious diseases. A homologous prime-boost vaccination approach, consisting of a non-replicating chimpanzee adenovirus (ChAd) prime vector and boost has been shown to be effective in Sars-cov-2 vaccination. The ChAdOxI nCoV-19 vaccine - developed by Oxford’s Clinical BioManufacturing Facility (CBM) - is estimated to have saved 6.3 million lives in the first year of the pandemic (Falsey et al. 2021). The ChAd prime-boost strategy is being used to prevent Ebola, respiratory syncytial virus (RSV), hepatitis C virus (HCV), hepatitis B virus (HBV) (NCT04297917), as well as preventing non-viral infective diseases such as malaria. In large population-based studies, Homologous (Chad-ChAd (prime / booster)) vaccination has shown to be effective in increasing population immunity against Covid-19 (Nordstrom et al. 2021), though with lower efficacy compared to heterologous schedules in which ChAdOx prime is followed by mRNA boost. Each approach provides its own advantages. In the present context, the use of a ChAdOx / ChadOx combination is believed to be particularly advantageous as ChAdOX is better than mRNA for generating polyfunctional T cell immunity, whereas the use of mRNA-based vaccines is known to be particularly good for generating antibodies.

[0099] In clinical studies of the compositions of the disclosure, patients may be administered a vaccine containing the neoantigens linked to KRAS / EGFR / TP53 driver mutations intramuscularly IM over >2, or >3 (e.g. 4) doses to activate a robust T cell response to recognise and kill any cells bearing these mutations. In this way, the vaccine has been developed to prevent similar cancers from forming or returning in these patients. Specifically, the vaccine in clinical trial is comprised of MUC1-NYESO1-P53 concatenated mutations-KRAS concatenated mutations-EGFR concatenated mutations packaged in ChAdOx2 vector (here abbreviated to ‘ChAdOx2-lungvax- NYESO’).

[0100] While the inventors chose the ChAdOx2 vaccine platform for initial studies, the inventors envisage that any suitable vaccine platform or delivery mechanism could be used with the antigens presented herein. Such vaccine platforms are known to the person skilled in the art, and may include, for example, cell-based (e.g. antigen-presenting cells), virus / bacteria-based (e.g. viruslike particles), gene-based (e.g. DNA, RNA), and peptide-based vaccines.

[0101] In particular, the vector may be a ChAdOx vector, such as ChAdOxI or ChAdOx2. “ChAdOxI” as used herein is a viral vector based on Chimpanzee adenovirus C68 developed by the Jenner Institute, University of Oxford. ChAdOxI is described in Dicks et al. (2012), and in WO2012 / 172277, both of which are incorporated herein by reference in their entirety. “ChAdOx2” as used herein is a Chimpanzee Adenovirus vector that uses the same C68 backbone as ChAdOxI , with the serotype 5 (AdHu5) E4 orf6 / 7 region in place of the AdC68 equivalents. ChAdOx2 is described in Wang et al. (2018), which is incorporated herein by reference in its entirety.

[0102] The vector may be a modified vaccinia Ankara (MVA) vector. “Modified vaccinia virus Ankara (MVA) vector” as used herein is an attenuated replication-deficient vaccinia virus that has been genetically modified to include in its genome foreign DNA. In particular, the MVA vector may be genetically modified to express neoantigens and optionally TAAs as described herein. Thus, the MVA vector may refer to viral particles of MVA that comprise inside the viral particle the MVA genome, and coding sequences for antigenic peptides as described introduced in the MVA genome.

[0103] The vector may be non-viral. Non-viral vectors may be particularly suited for cases where the nucleic acid is mRNA. The non-viral vector may be a nanoparticle, such as a lipid nanoparticle (LNP), polymer-based nanoparticle, inorganic nanoparticle, hybrid nanoparticle or dendrimer.

[0104] The use of nanoparticles for mRNA vaccine delivery was recently reviewed in Parvin et al., 2024. Vaccine platforms and delivery systems for cancer vaccines, both viral and non-viral, have been recently reviewed in Ruzzi et al., 2024. The mRNA vaccine may be a non-replicating mRNA vaccine. Non-replicating mRNA vaccines are the most common type of mRNA vaccines, and include a single mRNA strand encoding the antigen(s) packaged in a delivery vector. Once delivered into the cells, the mRNA is translated by ribosomes into the target protein. The resultant protein then triggers an adaptive immune response. Non-replicating mRNA vaccines may be particularly advantageous as they are simple to design and manufacture, and are well suited to rapid vaccine development. Examples of non-replicating mRNA vaccines include “Comirnaty” COVID-19 mRNA Vaccine BNT162b2 (EMEA / H / C / 005735) or “Spikevax” COVID-19 Vaccine Moderna mRNA-1273 (EMEA / H / C / 005791). The mRNA vaccine may be a self-amplifying mRNA vaccine (saRNA). In addition to the mRNA sequence encoding the antigen(s), saRNA includes sequences for replication machinery (e.g. derived from alphavirus RNA replicons). Once inside the cell, the replication machinery amplifies the mRNA, producing more copies of the antigen(s)- encoding mRNA, resulting in higher antigen expression with a smaller initial vaccine dose, and the potential for enhanced and prolonged antigen expression. An saRNA may be particularly advantageous for a cancer vaccine, in that it may provide enhanced and prolonged antigen expression. The mRNA vaccine may further be a circular RNA (circRNA) vaccine. A circRNA vaccine may be particularly advantageous in that the circularisation of RNA (mRNA) increases its resistance to exonuclease degradation, increasing its stability, and therefore may result in increased persistence of the RNA in cells. The mRNA vaccine may comprise a single strand of mRNA, or two or more strands of mRNA. Advantageously, the mRNA vaccine may comprise a single strand of mRNA, to allow for easier manufacturing, increased stability in storage and in vivo, as well as encouraging uniform expression of the one or more antigens comprised therein. The mRNA sequence may be codon optimised as described herein to advantageously enhance translation efficiency and protein expression in human cells. The mRNA sequence may include untranslated regions (UTRs) at the 5’ and / or 3’ end, preferably comprising genes with naturally high expression in the host, to encourage increased expression of the antigenic mRNA sequence(s) comprised within the same construct. The mRNA sequence may comprise a polyA tail, which may be at least 20, at least 50, at least 100, at least 110, at least 120, at least 150, or at least 200 contiguous nucleotides in length. The polyA tail may also be non-contiguous. The mRNA sequence may advantageously incorporate modified nucleosides like pseudouridine and 5- methylcytidine to reduce immunogenicity and enhance mRNA stability by reducing degradation by exo- or endonucleases.

[0105] Lipid formulations for LNPs are known in the art. Such lipid formulations commonly comprise ionizable lipids, phospholipids, cholesterol, and / or PEGylated lipids. Ionizable lipids are the main lipid used for mRNA encapsulation, protecting the mRNA from degradation, and also aid in endosomal escape. Endosomal escape is facilitated by the lipids becoming positively charged in the acidic environment of the endosome, allowing for membrane fusion and release of the mRNA payload into the cytoplasm. Examples most commonly include ALC-0315 ([(4- Hydroxybutyl)azanediyl]di(hexane-6,1-diyl) bis(2-hexyldecanoate), PubChem CID: 122666778) and SM-102 (9-Heptadecanyl 8-{(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino}octanoate, PubChem CID: 126697616). Further examples include MC3 ((6Z,9Z,28Z,31Z)-Heptatriaconta- 6,9,28,31 -tetraen-19-yl 4-(dimethylamino)butanoate, D-Lin-MC3-DMA, CAS: 1224606-06-7), C12- 200 (1 ,1 '-[[2-[4-[2-[[2-[b / s(2-hydroxydodecyl)amino]ethyl](2-hydroxydodecyl)amino]ethyl]-1- piperazinyl]ethyl]imino]b / s-2-dodecanol, CAS: 1220890-25-4), and C14-4 (1 ,1 '-[[2-[2-[4-[2-[[2-[2- [bis(2-hydroxytetradecyl)amino]ethoxy]ethyl](2-hydroxytetradecyl)amino]ethyl]-1- piperazinyl]ethoxy]ethyl]imino]bis-2-tetradecanol, c14-494, Lipid B4, CAS: 2639634-80-1). Selection and optimisation of lipid formulation is well known in the art, and any such selection or combination of ionizable lipids may be used. Phospholipids may be included for structural integrity and aiding with cell membrane fusion. Saturated phospholipids such as DSPC and DPPC enhance nanoparticle rigidity and stability, while unsaturated phospholipids such as DOPE and DOPC improve fusion and delivery. Examples most commonly include 1 ,2-Distearoyl-sn-glycero-3- phosphocholine (DSPC) and 1 ,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Further examples include 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-Stearoyl-2-oleoyl- sn-glycero-3-phosphocholine (SOPC), Egg Phosphatidylcholine (EPC), 1 ,2-Dioleoyl-sn-glycero-3- phosphocholine (DOPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), and 1 ,2- Dioleoyl-3-trimethylammonium-propane (DOTAP). Selection and optimisation of lipid formulation is well known in the art, and any such selection or combination of phospholipids may be used. The inclusion of cholesterol in LNP formulation advantageously improves the structural stability and membrane fluidity of the LNP, as well as facilitating endosomal escape and improving membrane biocompatibility. Cholesterol may be synthetic, plant-derived, or animal-derived. Cholesterol is preferably synthetic. PEGylated lipids may be included in the LNP formulation. PEGylated lipids advantageously improve circulation time of the LNP, by forming a hydrophilic coating thus reducing recognition and clearance by the immune system, increasing the half-life of LNPs in the bloodstream. The hydrophilic coating further advantageously prevents aggregation and opsonisation of the LNP to further improve stability during systemic circulation. PEGylated lipids may also advantageously reduce immunogenicity, by minimising interaction between LNPs and immune cells. Examples commonly include ALC-0159 (2-[(polyethylene glycol)-2000]-N,N- ditetradecylacetamide, CAS: 1849616-42-7), (PEG-DMG (DMG-PEG 2000, Polyethylene Glycol- Dimyristoyl Glycerol, 1 ,2-Dimyristoyl-sn-glycero-3-methoxypolyethylene glycol, PubChem CID: 122629501). PEGylated lipids may be included in the LNP formulation at around 1-5% of the total lipid content. The LNPs may additionally include targeting ligands, such as antibodies, peptides, or aptamers, in order to enhance cell specificity of the LNP. Each LNP may comprise 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 copies of the mRNA construct. The number of mRNA molecules that can be encapsulated in a LNP is dependent on the length of the mRNA. Where the length of the mRNA is between 1000 nt and 2000 nt, the average payload can be expected to be between 2 and 3 mRNA molecules per LNP. Preferably, each LNP comprises more than one mRNA molecule. Vectors, nucleic acids and immunogenic compositions according to the present disclosure comprise a plurality of antigens or coding sequences for a plurality of antigens that are associated with mutations in at least two of TP53, KRAS and EGFR. In embodiments, a vector or composition according to the present disclosure comprises antigens or coding sequences for antigens associated with mutations in each of TP53, KRAS and EGFR. In embodiments, a vector or composition according to the disclosure comprises a plurality of antigens or coding sequences for a plurality of antigens, each antigen associated with a mutation in TP53, KRAS or EGFR. In embodiments, a vector or composition according to the present disclosure comprises a plurality of antigens or coding sequences for a plurality of antigens comprising multiple antigens associated with respective mutations in TP53, multiple antigens associated with respective mutations in KRAS, and multiple antigens associated with respective mutations in EGFR. These sequences and antigens may be referred to interchangeably as “neoantigens”. The vectors comprise nucleotide sequence that encodes antigenic protein sequences (also referred to simply as “antigens”). The term “antigenic protein” or “antigen” as used herein encompasses neoantigens and tumour associated antigens. The sequence encoding the antigens may be introduced into the vectorat a specific location, using molecular cloning, or the vectors may be synthesised to produce a nucleic acid comprising the vector backbone sequence and nucleotide sequence encoding antigenic protein sequences. The vectors or compositions may comprise between 2 and 24 neoantigens or nucleotide sequence that encodes between 2 and 24 neoantigens. For example, the vectors or compositions may comprise 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 neoantigens or sequences encoding for 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 neoantigens. Advantageously, the more neoantigens present within a vector or composition, the greater the likely coverage of a particular cancer population, and hence the greater the likelihood that an immunogenic composition as described herein will generate an immune response in a subject than can protect said subject from developing lung cancer. For example, when 5 antigens are present in a vector or composition, the subject will have immunity against cancer cells presenting any one of those 5 antigens, and when there are 10 antigens present in a vector or composition, the subject will have immunity against cancer cells presenting any one of those 10 antigens. The probability that a subject will have immunity against cancer cells is expected to correlate with the prevalence of the mutations giving rise to the neoantigens included in the vector or composition, among cancer patients. In other words, each mutation is associated with a particular coverage in a population of cancer patients, which refers to the percentage of patients in the population that have the mutation. The particular antigens used in vectors and compositions of the disclosure were selected specifically to provide high coverage in particular in lung cancer patients.

[0106] The plurality of antigens associated with mutations in at least two genes selected from TP53, KRAS and EGFR may be selected from the hotspot mutations as defined herein, and as listed in Tables 1 , 2 and 3 (column “mutation”). The plurality of antigens associated with mutations in at least two genes selected from TP53, KRAS and EGFR may be selected from Table 1 , Table 2, Table 3 and / or Figure 2. Advantageously, the plurality of antigens associated with mutations in at least two genes selected from TP53, KRAS and EGFR may be selected from Table 1 or Figure 2, which have proven ability to elicit T cell reactivity. In embodiments, the plurality of antigens associated with mutations in at least two genes selected from TP53, KRAS and EGFR are antigens associated with mutations selected from: EGFR_E746_A750del, KRAS_G12A, KRAS_G12C, KRAS_G12D, KRAS_G12R, KRAS_G12V, EGFR_L858R, TP53_R175H, TP53_R248Q, TP53_R248W, EGFR_T790M, TP53_Y220C. All of these have been proven to be able to elicit T cell reactivity. In embodiments, the plurality of antigens associated with mutations in at least two genes selected from TP53, KRAS and EGFR are antigens associated with mutations selected from: EGFR_L861Q, KRAS_G13C, KRAS_G13D, TP53_R273L, TP53_G245C, TP53_R158L, TP53_V157F, TP53_R273H, TP53_R273C, TP53_Y234C. All of these have been predicted to be associated with antigen peptides that have strong HLA binding affinity. In embodiments, the plurality of antigens associated with mutations in at least two genes selected from TP53, KRAS and EGFR are antigens associated with mutations selected from: EGFR_E746_A750del, KRAS_G12A, KRAS_G12C, KRAS_G12D, KRAS_G12R, KRAS_G12V, EGFR_L858R,

[0107] TP53_R175H, TP53_R248Q, TP53_R248W, EGFR_T790M, TP53_Y220C, EGFR_L861 Q, KRAS_G13C, KRAS_G13D, TP53_R273L, TP53_G245C, TP53_R158L, TP53_V157F,

[0108] TP53_R273H, TP53_R273C, TP53_Y234C. In embodiments, the plurality of antigens associated with mutations in TP53 are antigens associated with mutations selected from: P53_R175H, TP53_R248Q, TP53_R248W, TP53_Y220C, TP53_R273L, TP53_G245C, TP53_R158L, TP53_V157F, TP53_R273H, TP53_R273C, TP53_Y234C. In embodiments, the plurality of antigens associated with mutations in KRAS are antigens associated with mutations selected from: KRAS_G12A, KRAS_G12C, KRAS_G12D, KRAS_G12R, KRAS_G12V, KRAS_G13C, KRAS_G13D. In embodiments, the plurality of antigens associated with mutations in EGFR are antigens associated with mutations selected from: EGFR_E746_A750del, EGFR_L858R, EGFR_T790M, EGFR_L861 Q.

[0109] The vectors, nucleic acids and immunogenic compositions as described herein may comprise antigens or coding sequences for antigens associated with at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11 , at least 12, at least 16, at least 19, or at least 22 hotspot mutations. The vectors and immunogenic compositions as described herein may comprise 22 antigens associated with hotspot mutations as described herein. The vectors and immunogenic compositions as described herein may comprise coding sequences for antigens associated with at least 5 hotspot mutations selected from those listed in Table 1 (column “mutations”). The present inventors have demonstrated that any 5 mutations selected from those hotspot mutations is associated with a coverage in lung adenocarcinoma patients of over 30%. This means that over 30% of patients at risk of developing lung adenocarcinoma who receive an immunogenic composition as described herein are expected to be protected at least to some extent from developing lung adenocarcinoma. This represents a significant proportion of cancers that can potentially be prevented. The vectors and immunogenic compositions as described herein may comprise coding sequences for antigens associated with at least 10 hotspot mutations selected from those listed in Table 1 (column “mutations”). The present inventors have demonstrated that any 10 mutations selected from those hotspot mutations is associated with a coverage in lung adenocarcinoma patients of over 40%. The vectors and immunogenic compositions as described herein may comprise coding sequences for antigens associated with at least 15 hotspot mutations selected from those listed in Table 1 (column “mutations”). The present inventors have demonstrated that any 15 mutations selected from those hotspot mutations is associated with a coverage in lung adenocarcinoma patients of over 50%. As used herein, patient coverage (referred to interchangeably as “coverage”) in the context of the vectors and immunogenic compositions described herein refers to the proportion of cancer patients in a population (e.g. lung cancer patients, or more specifically lung adenocarcinoma patients) which have tumours positive for at least one of the antigens associated with mutations that are included within the vector, or their tumour is positive for at least one TAA included within the vector. The vaccine may provide a patient coverage of at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65% or at least 70%. Preferably, the patient coverage may be at least 70% for a population of NSCLC patients. The patient coverage may be determined by how many antigens associated with mutations are present in the vaccine. The patient coverage may be determined by limiting the patient population to those patients with a specific disease, such as limiting to patients having Lung Adenocarcinoma, or limiting to patients having NSCLC. The vector may contain coding sequences for one or more TAAs. When the vector comprises coding sequences for one or more TAAs, the patient coverage may be increased. When the vector comprises coding sequences for one or more TAAs, the vector may provide immunity against cancer cells which express the TAA, whether or not they express any of the antigens associated with mutations that are included within the vector.

[0110] In embodiments, the vectors, nucleic acids or compositions as described herein comprises a plurality of antigens or coding sequences for a plurality of antigens comprising one or more antigens associated with respective mutations in KRAS, and one or more antigens associated with respective mutations in EGFR. The vectors and immunogenic compositions as described herein may comprise antigens or coding sequences for antigens associated with a plurality of mutations in KRAS selected from Table 1 , and a plurality of mutations in EGFR selected from Table 1. The vectors and immunogenic compositions as described herein may comprise antigens or coding sequences for antigens associated with mutations KRAS_G12C and EGFR_L858R, and one or more tumour associated antigens as described herein. Use of antigens associated with KRAS_G12C and EGFR_L858R, would provide a coverage of at least 20% for a population of LUAD patients and almost 20% for lung cancer overall (Table 1). Alternative combinations of antigens may be selected from Tables 1 and 2 to achieve a coverage of at least 20% in LUAD. For example, a vector or immunogenic composition comprising antigens or coding sequences thereof associated with KRAS_G12V, KRAS_G12D, KRAS_G12A and EGFR_L858R mutations would also provide a coverage of at least 20% for a population of LUAD patients (Table 2). Note that the coverage provided in Tables 1 and 2 is for single mutations and is therefore not strictly speaking additive. However, patients with multiple mutations in Table 2 are relatively rare such that adding the percentages in Table 2 provides a good estimate of the expected coverage in the population at hand. The vectors and immunogenic compositions as described herein may comprise antigens or coding sequences for antigens associated with KRAS_G12C, EGFR_L858R, and KRAS_G12V mutations. A vector or immunogenic composition comprising antigens or coding sequences thereof associated with KRAS_G12C, EGFR_L858R, and KRAS_G12V mutations would provide a coverage of almost 30% for a population of LUAD patients (Table 1). Alternative combinations of antigens may be selected to achieve a coverage of at least 30%, based on Table 2. For example, a vector comprising antigens associated with KRAS_G12C, EGFR_L858R, KRAS_G12D and KRAS_G12A mutations would also provide a coverage of at least 30% for a population of LUAD patients (Table 2). The vectors and immunogenic compositions as described herein may comprise antigens or coding sequences for antigens associated with KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, and KRAS_G12A mutations. A vector or immunogenic composition comprising antigens or coding sequences thereof associated with KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, and KRAS_G12A mutations would provide a coverage of at least 40% fora population of LUAD patients (Table 1). Alternative combinations of antigens may be selected to achieve a coverage of at least 40%, based on Table 2. For example, a vector comprising antigens associated with KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del and EGFR_T790M would also provide a coverage of at least 40% for a population of LUAD patients (Table 2). The vectors and immunogenic compositions as described herein may comprise antigens or coding sequences for antigens associated with a plurality of mutations in KRAS selected from those in Table 1 , a plurality of mutations in EGFR selected from those in Table 1 , and a plurality of mutations in TP53 selected from those in Table 1. The vectors and immunogenic compositions as described herein may comprise antigens or coding sequences forantigens associated with KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, EGFR_E746_A750del, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H, TP53_R273C, EGFR_L861Q, TP53_R248Q, and TP53_R248W mutations. A vector or immunogenic composition comprising antigens or coding sequences thereof associated with KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, EGFR_E746_A750del, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H, TP53_R273C, EGFR_L861Q, TP53_R248Q, and TP53_R248W mutations would provide a coverage of at least 50% for a population of LUAD patients (Table 2).

[0111] In embodiments, the vectors, nucleic acids and immunogenic compositions described herein comprise an antigen or coding sequence for an antigen associated with the KRAS_G12C mutation. Immunising subjects using a vector or immunogenic composition comprising this antigen or the coding sequence for this antigen provides a coverage of at least 15% in a population of patients at risk of developing LUAD, and at least 13% in a population at risk of developing any type of lung cancer. In embodiments, the vectors, nucleic acids and immunogenic compositions described herein comprise an antigen or coding sequence for an antigen associated with the EGFR_L858R mutation. Immunising subjects using a vector or immunogenic composition comprising this antigen or the coding sequence for this antigen provides a coverage of at least 10% in a population of patients at risk of developing LUAD, and at least 8% in a population at risk of developing any type of lung cancer. In embodiments, the vectors and immunogenic compositions described herein comprise an antigen or coding sequence for an antigen associated with the KRAS_G12V mutation. Immunising subjects using a vector or composition comprising this antigen or a sequence coding for this antigen provides a coverage of at least 7% in a population of patients at risk of developing LUAD and at least 6% in a population at risk of developing any type of lung cancer. In embodiments, the vectors and immunogenic compositions described herein comprise an antigen or coding sequence for an antigen associated with the KRAS_G12D mutation. Immunising subjects using a vector or immunogenic composition comprising this antigen or coding sequence provides a coverage of at least 5% in a population of patients at risk of developing LUAD, and at least 4% in a population at risk of developing any type of lung cancer. In embodiments, the vectors and immunogenic compositions described herein comprise an antigen or coding sequence for an antigen associated with the EGFR_E746_A750del mutation. Immunising subjects using a vector or composition comprising this antigen or coding sequence provides a coverage of at least 5% in a population of patients at risk of developing LUAD, and at least 4% in a population at risk of developing any type of lung cancer. In embodiments,

[0112] In embodiments, a vector, nucleic acid or composition as described herein comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, EGFR_E746_A750del, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H, TP53_R273C, EGFR_L861 Q, TP53_R248Q, TP53_R248W, TP53_Y220C, TP53_G245C, TP53_R273H, KRAS_G12R, and TP53_Y234C. Any one or more of these mutations may be excluded, provided that the vector or composition still comprises antigens or coding sequences for antigens associated with a plurality of mutations including mutations in at least two or EGFR, TP53 and KRAS. For example, one or more mutations may be excluded from the above to reduce antigen competition and / or simplify manufacturing. For example, in embodiments, a vector or composition as described herein comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H, TP53_R273C, EGFR_L861 Q, TP53_R248Q, TP53_R248W, TP53_Y220C, TP53_G245C, TP53_R273H, and KRAS_G12R. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H, TP53_R273C, EGFR_L861Q, TP53_R248Q, TP53_R248W, TP53_Y220C, TP53_G245C, and TP53_R273H. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H, TP53_R273C, EGFR_L861Q, TP53_R248Q, TP53_R248W, TP53_Y220C, and TP53_G245C. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H, TP53_R273C, EGFR_L861Q, TP53_R248Q, TP53_R248W, and TP53_Y220C. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H, TP53_R273C, EGFR_L861Q, TP53_R248Q, TP53_R248W. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H, TP53_R273C, EGFR_L861Q, TP53_R248Q. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H, TP53_R273C, EGFR_L861Q. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H, TP53_R273C. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L, TP53_V157F. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_E746_A750del. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R, KRAS_G12V. As another example, a vector or composition as described herein may comprises a plurality of antigens or coding sequences for a plurality of antigens associated with the following mutations: KRAS_G12C, EGFR_L858R.

[0113] In embodiments, a vector, nucleic acid or composition as described herein comprises a plurality of antigens or coding sequences for a plurality of antigens associated with at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11 , at least 12, at least 13, at least 14 or at least 15 of the following mutations: KRAS_G12C, EGFR_L858R,

[0114] KRAS_G12V, KRAS_G12D, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M,

[0115] EGFR_E746_A750del, TP53_R158L, TP53_R273L, TP53_V157F, KRAS_G13C, KRAS_G13D, TP53_R175H, TP53_R273C, EGFR_L861 Q, TP53_R248Q, TP53_R248W, TP53_Y220C, TP53_G245C, TP53_R273H, KRAS_G12R, and TP53_Y234C. As is apparent from the content of

[0116] Table 2 below, multiple combinations of the above set of mutations can be used to reach a desired coverage in lung cancer and / or LUAD. For example, any of the sets of mutations below can be used to achieve a coverage of at least 30% of LUAD patients (with coverage % calculated in the

[0117] MSKCC GENIE LUAD cohort provided in brackets), and any of these combinations is explicitly envisaged herein, as are any combinations including these mutations and additional mutations: KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D (40.65243902); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A (38.24390244); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C (36.82926829);

[0118] KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G12A (36.73170732); KRAS_G12C,

[0119] EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13D (36.65243902); KRAS_G12C,

[0120] EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, EGFR_L861Q (36.54878049); KRAS_G12C,

[0121] EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A (36.54268293); KRAS_G12C,

[0122] EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R273L (36.5); KRAS_G12C,

[0123] EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M (36.49390244); KRAS_G12C,

[0124] EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R158L (36.3902439); KRAS_G12C,

[0125] EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_V157F (36.36585366); KRAS_G12C,

[0126] EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R175H (36.22560976); KRAS_G12C,

[0127] EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53 R273C (36.22560976); KRAS_G12C,

[0128] EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_T790M (36.04878049); KRAS_G12C,

[0129] EGFR_L858R, EGFR_E746_A750del, KRAS_G12V (35.69512195); KRAS_G12C, EGFR_L858R,

[0130] KRAS_G12V, KRAS_G12D, KRAS_G13C (35.32926829); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G13D (35.15853659); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A (35.1402439); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C (35.12804878); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_L861Q (35.06707317); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R273L (35.01829268); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D (34.9695122); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R158L (34.90853659); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_V157F (34.87804878); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R273L (34.8597561); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_L861Q (34.85365854); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M (34.79878049); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R273C

[0131] (34.77439024); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R175H

[0132] (34.76219512); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R158L (34.74390244); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_V157F (34.7195122); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R175H (34.54878049); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R273C (34.5304878); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_T790M (34.23170732); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D (34.21341463); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D (34); KRAS_G12C,

[0133] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13C (33.7195122); KRAS_G12C,

[0134] EGFR_L858R, KRAS_G12V, KRAS_G12A, EGFR_T790M ( i 33.60365854); KRAS_G12C,

[0135] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13D (33.54268293); KRAS_G12C,

[0136] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_L861Q ! (33.47560976); KRAS_G12C,

[0137] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R273L (33.44512195); KRAS_G12C,

[0138] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R158L (33.31707317); KRAS_G12C,

[0139] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_V157F (33.29268293); KRAS_G12C,

[0140] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R175H (33.15853659); KRAS_G12C,

[0141] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53 R273C (33.15853659); KRAS_G12C,

[0142] EGFR_L858R, KRAS_G12V, KRAS_G12A, KRAS_G13C (32.90853659); KRAS_G12C,

[0143] EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, KRAS_G13C (32.73780488); KRAS_G12C,

[0144] EGFR_L858R, KRAS_G12V, KRAS_G12A, KRAS_G13D (32.72560976); KRAS_G12C,

[0145] EGFR_L858R, KRAS_G12V, KRAS_G12A, EGFR_L861Q (32.62195122); KRAS_G12C,

[0146] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D (32.60365854); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, KRAS_G13D (32.56707317); KRAS_G12C, EGFR_L858R,

[0147] KRAS_G12V, KRAS_G12A, TP53_R273L (32.54878049); KRAS_G12C, EGFR_L858R, KRAS_G12V,

[0148] KRAS_G12A, TP53_R158L (32.45731707); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12A, TP53_V157F (32.45121951); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, EGFR_L861Q (32.43902439); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, TP53_R273L (32.41463415); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M (32.37804878); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12A, TP53_R273C (32.35365854); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12A, TP53_R175H

[0149] (32.34756098); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, TP53_R158L

[0150] (32.32317073); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, TP53_V157F

[0151] (32.32317073); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, KRAS_G13C

[0152] (32.20121951); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, TP53_R175H

[0153] (32.15853659); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, TP53_R273C

[0154] (32.1402439); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, KRAS_G13D

[0155] (32.02439024); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, EGFR_T790M

[0156] (31.92073171); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, EGFR_L861Q

[0157] (31.8902439); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, TP53_R273L

[0158] (31.87195122); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, EGFR_T790M

[0159] (31.80487805); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, TP53_R158L

[0160] (31.7804878); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12A (31.77439024); KRAS_G12C,

[0161] EGFR_L858R, KRAS_G12V, EGFR_T790M, TP53_V157F (31.75609756); KRAS_G12C

[0162] EGFR_L858R, KRAS_G12V, EGFR_T790M, TP53_R175H (31.64634146); KRAS_G12C

[0163] EGFR_L858R, KRAS_G12V, EGFR_T790M, TP53_R273C (31.64634146); KRAS_G12C

[0164] EGFR_L858R, EGFR_E746_A750del, KRAS_G12A (31.59146341); KRAS_G12C, EGFR_L858R,

[0165] KRAS_G12V, KRAS_G13C, KRAS_G13D (31.32317073); KRAS_G12C, EGFR_E746_A750del,

[0166] KRAS_G12V, KRAS_G12A, KRAS_G13C (31.31707317); KRAS_G12C, KRAS_G12V, KRAS_G12D,

[0167] KRAS_G12A, EGFR_T790M (31.31097561); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, KRAS_G13C (31.22560976); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13C, EGFR_L861Q (31.21341463); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273L, KRAS_G13C (31.15853659); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13C, KRAS_G13D (31.14634146); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, KRAS_G13D (31.12804878); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M

[0168] (31.06707317); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, KRAS_G13D

[0169] (31.06097561); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R158L, KRAS_G13C

[0170] (31.05487805); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, EGFR_L861Q (31.04878049); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13D, EGFR_L861Q

[0171] (31.04268293); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_V157F, KRAS_G13C (31.03658537); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13C, EGFR_L861Q (31.01219512); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R273L, KRAS_G13C (31.01219512); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, TP53_R273L (30.99390244); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273L, KRAS_G13D (30.99390244); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, KRAS_G13C

[0172] (30.95731707); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13C, TP53_R273C

[0173] (30.95731707); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13C, TP53_R175H

[0174] (30.95121951); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, EGFR_L861Q

[0175] (30.94512195); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, TP53_R273L

[0176] (30.92682927); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R158L, KRAS_G13C

[0177] (30.90243902); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_V157F, KRAS_G13C

[0178] (30.8902439); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R158L, KRAS_G13D (30.8902439); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273L, EGFR_L861Q (30.8902439); KRAS_G12C,

[0179] EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, TP53_R158L (30.88414634); KRAS_G12C,

[0180] EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, TP53_V157F (30.88414634); KRAS_G12C,

[0181] EGFR_L858R, KRAS_G12V, TP53_V157F, KRAS_G13D (30.87195122); KRAS_G12C,

[0182] EGFR_L858R, EGFR_E746_A750del, TP53_R273L, KRAS_G13D (30.8597561); KRAS_G12C,

[0183] EGFR_L858R, EGFR_E746_A750del, KRAS_G13D, EGFR_L861Q (30.85365854); KRAS_G12C,

[0184] EGFR_L858R, KRAS_G12D, KRAS_G12A, TP53_R158L (30.82926829); KRAS_G12C,

[0185] EGFR_L858R, KRAS_G12D, KRAS_G12A, TP53_V157F (30.82317073); KRAS_G12C,

[0186] EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, KRAS_G13D (30.79878049); KRAS_G12C,

[0187] EGFR_L858R, KRAS_G12V, KRAS_G13D, TP53_R175H (30.78658537); KRAS_G12C,

[0188] EGFR_L858R, KRAS_G12V, KRAS_G13D, TP53_R273C (30.78658537); KRAS_G12C,

[0189] EGFR_L858R, KRAS_G12V, TP53_R158L, EGFR_L861Q (30.78658537); KRAS_G12C,

[0190] EGFR_L858R, KRAS_G12V, TP53_R158L, TP53_R273L (30.76219512); KRAS_G12C,

[0191] EGFR_L858R, KRAS_G12V, TP53_V157F, EGFR_L861Q (30.76219512); KRAS_G12C,

[0192] EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, TP53_R175H (30.75609756); KRAS_G12C,

[0193] EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, TP53_R273C (30.75609756); KRAS_G12C,

[0194] EGFR_L858R, EGFR_E746_A750del, TP53_R158L, KRAS_G13D (30.75); KRAS_G12C,

[0195] EGFR_L858R, EGFR_E746_A750del, KRAS_G13C, TP53_R175H (30.74390244); KRAS_G12C,

[0196] EGFR_L858R, KRAS_G12V, TP53_V157F, TP53_R273L (30.74390244); KRAS_G12C,

[0197] EGFR_L858R, EGFR_E746_A750del, TP53_V157F, KRAS_G13D (30.73780488); KRAS_G12C,

[0198] EGFR_L858R, EGFR_E746_A750del, TP53_R273L, EGFR_L861Q (30.73170732); KRAS_G12C,

[0199] EGFR_L858R, EGFR_E746_A750del, KRAS_G13C, TP53_R273C (30.72560976); KRAS_G12C,

[0200] EGFR_L858R, KRAS_G12D, KRAS_G12A, TP53_R175H (30.68292683); KRAS_G12C,

[0201] EGFR_L858R, KRAS_G12D, KRAS_G12A, TP53_R273C (30.67682927); KRAS_G12C,

[0202] EGFR_L858R, KRAS_G12V, TP53_R175H, EGFR_L861Q (30.67682927); KRAS_G12C,

[0203] EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, TP53_R273L (30.67073171); KRAS_G12C,

[0204] EGFR_L858R, KRAS_G12V, TP53_R273C, EGFR_L861Q (30.66463415); KRAS_G12C,

[0205] EGFR_L858R, EGFR_E746_A750del, TP53_R158L, TP53_R273L (30.65243902); KRAS_G12C,

[0206] EGFR_L858R, EGFR_E746_A750del, TP53_V157F, TP53_R273L (30.6402439); KRAS_G12C,

[0207] EGFR_L858R, KRAS_G12V, TP53_R158L, TP53_V157F (30.6402439); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273L, TP53_R175H (30.6402439); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273L, TP53_R273C (30.6402439); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, EGFR_L861Q (30.63414634); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R158L, EGFR_L861Q (30.62195122); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_V157F, EGFR_L861Q (30.60365854); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13D, TP53_R175H (30.59146341); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, TP53_R158L (30.57926829); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, TP53_V157F (30.56707317); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13D, TP53_R273C (30.56707317); KRAS_G12C, EGFR_L858R, KRAS_G12V,

[0208] TP53_R158L, TP53_R273C (30.54268293); KRAS_G12C, EGFR_L858R, KRAS_G12V,

[0209] TP53_R158L, TP53_R175H (30.53658537); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del,

[0210] TP53_R158L, TP53_V157F (30.5304878); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_V157F, TP53_R175H (30.52439024); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_V157F, TP53_R273C

[0211] (30.52439024); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, KRAS_G13C (30.51829268); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R273L, TP53_R175H (30.47560976); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R175H, EGFR_L861Q (30.45731707); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R273L, TP53_R273C (30.45121951); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R273C, EGFR_L861Q (30.42073171); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R175H, TP53_R273C (30.42073171); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, TP53_R175H (30.39634146); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, KRAS_G13C (30.37804878); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, TP53_R273C (30.37195122); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R158L, TP53_R175H (30.36585366); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_V157F, TP53_R175H (30.3597561); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, KRAS_G13D

[0212] (30.3597561); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13C (30.3597561); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R158L, TP53_R273C (30.34756098); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_V157F, TP53_R273C (30.33536585); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, TP53_R273L (30.25609756); KRAS_G12C,

[0213] EGFR_L858R, KRAS_G12D, EGFR_T790M, EGFR_L861Q (30.21341463); KRAS_G12C,

[0214] EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, KRAS_G13D (30.20121951); KRAS_G12C,

[0215] EGFR_L858R, KRAS_G12V, KRAS_G13D (30.18902439); KRAS_G12C, EGFR_E746_A750del,

[0216] KRAS_G12V, KRAS_G12A (30.18292683); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R175H, TP53_R273C (30.17073171); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del,

[0217] KRAS_G13C (30.15853659); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M,

[0218] TP53_R158L (30.15243902); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M,

[0219] TP53_V157F (30.12804878); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A

[0220] (30.09756098); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, EGFR_T790M

[0221] (30.09146341); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, EGFR_L861Q

[0222] (30.08536585); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_R273L

[0223] (30.08536585); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_L861Q (30.07926829); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273L (30.04268293); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13D (30). Similarly, when an expected coverage of at least 20% of LUAD patients is considered sufficient, then in addition to the sets above any of the following combinations could also be used (with coverage % calculated in the MSKCC GENIE LUAD cohort provided in brackets), and are explicitly envisaged herein, as are any combinations including these mutations and additional mutations: KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, TP53_R175H (29.98170732); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_R158L (29.97560976); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, TP53_R273C (29.9695122); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_V157F (29.95731707); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R158L (29.94512195); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_V157F (29.92682927);

[0224] KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, KRAS G13C (29.90243902); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R273L (29.88414634); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_L861 Q (29.86585366); KRAS_G12C,

[0225] EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_R273C (29.82926829); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_R175H (29.82317073); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R175H (29.82317073); KRAS_G12C, EGFR_L858R,

[0226] KRAS_G12V, TP53_R273C (29.82317073); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M (29.81097561); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R158L (29.7804878); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_V157F (29.76829268);

[0227] KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, KRAS_G13C (29.76829268); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, KRAS_G13D (29.72560976); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C, KRAS_G13D (29.70121951); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13C, KRAS_G13D (29.65853659); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, EGFR_L861 Q (29.62804878); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R273L (29.62804878); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C, EGFR_L861 Q (29.61585366); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, KRAS_G13C (29.60365854); KRAS_G12C, EGFR_L858R,

[0228] EGFR_E746_A750del, TP53_R175H (29.60365854); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, KRAS_G13D (29.58536585); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273L, KRAS_G13C (29.57926829); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R273C (29.57926829); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273L, KRAS_G13C (29.54268293); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13C, EGFR_L861 Q (29.53658537); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, EGFR_L861 Q (29.51829268); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R158L (29.51219512); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_V157F (29.48170732); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R273L (29.46341463); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, KRAS_G13C (29.45731707); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, KRAS_G13C

[0229] (29.44512195); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13D, EGFR_L861 Q (29.43902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, KRAS_G13D (29.43292683); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, KRAS_G13C (29.42682927); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273L, KRAS_G13D (29.40853659); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_V157F, KRAS_G13C (29.40853659); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A (29.39634146); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273L, KRAS_G13D (29.39634146); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M (29.3902439);

[0230] KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R273C (29.3902439); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13D, EGFR_L861 Q (29.38414634); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R175H (29.37195122); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R158L (29.35365854); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_V157F (29.34756098); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, EGFR_L861 Q (29.34146341); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_R273L (29.33536585); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C, TP53_R175H (29.33536585); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C, TP53_R273C (29.33536585); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273L, EGFR L861 Q (29.32926829); KRAS_G12C, EGFR_E746_A750del,

[0231] KRAS_G12V, TP53_R158L, KRAS_G13D (29.28658537); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13C, TP53_R175H (29.28658537); KRAS_G12C, EGFR_L858R, KRAS_G12D,

[0232] KRAS_G13C, TP53_R273C (29.2804878); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, KRAS_G13D (29.2804878); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273L, EGFR_L861 Q (29.2804878); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, KRAS_G13D (29.27439024); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_V157F, KRAS_G13D (29.26219512); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R273C

[0233] (29.25609756); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M (29.24390244);

[0234] KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R175H (29.24390244); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_R158L (29.22560976); KRAS_G12C,

[0235] EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_V157F (29.22560976); KRAS_G12C, EGFR_L858R, KRAS_G12V (29.22560976); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, EGFR_L861 Q (29.20731707); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V,

[0236] TP53_R158L, TP53_R273L (29.20121951); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, TP53_R273L (29.20121951); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, EGFR_L861 Q (29.18902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, TP53_R273L (29.18902439); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_V157F, TP53_R273L (29.18292683); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13D, TP53_R175H (29.16463415); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, EGFR_L861 Q (29.16463415); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13D, TP53_R273C (29.15853659); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13D, TP53 R175H

[0237] (29.1402439); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_V157F, EGFR_L861 Q (29.1402439);

[0238] KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13D, TP53_R273C (29.12804878); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R175H, EGFR_L861 Q (29.07926829); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_R175H (29.06707317); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, TP53_V157F (29.06707317); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, TP53_V157F (29.06707317); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273C, EGFR_L861 Q (29.06097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273L, TP53_R175H (29.06097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273L, TP53_R273C (29.05487805); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_R273C (29.04878049); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273L, TP53 R175H (29.04268293);

[0239] KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273L, TP53_R273C (29.0304878); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R175H, EGFR_L861 Q (29.01829268); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del (29.01219512); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273C, EGFR_L861 Q (28.99390244); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, TP53_R175H (28.93902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, TP53_R273C (28.93902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, TP53_R175H (28.93292683); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, TP53_R273C (28.92682927); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, TP53_R175H (28.92682927); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, TP53 R273C (28.92073171); KRAS_G12C, EGFR_L858R, KRAS_G12D,

[0240] TP53_V157F, TP53_R175H (28.91463415); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_V157F, TP53_R273C (28.90243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R175H, TP53_R273C (28.79878049); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M

[0241] (28.78658537); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R175H, TP53_R273C

[0242] (28.76219512); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C (28.74390244); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13C (28.68292683); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, KRAS_G13C (28.67073171); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A (28.65243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13D (28.56707317); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13D (28.5304878); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, KRAS_G13D (28.51219512); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_L861 Q (28.48170732); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A (28.47560976); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273L (28.46341463); KRAS_G12C,

[0243] EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_R273L (28.43902439); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273L (28.43292683); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_L861 Q (28.40853659); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, EGFR_L861 Q (28.38414634); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L (28.34756098); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_V157F (28.33536585); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_R158L

[0244] (28.32317073); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L (28.32317073); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_V157F (28.30487805); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_V157F (28.30487805); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R175H (28.20731707); KRAS_G12C,

[0245] EGFR_E746_A750del, KRAS_G12V, TP53_R273C (28.20121951); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13C, KRAS_G13D (28.17682927); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R175H (28.16463415); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273C (28.15243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_R175H (28.1402439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_R273C (28.12804878); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13C, EGFR_L861 Q

[0246] (28.10365854); KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M, KRAS_G13C

[0247] (28.09146341); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R273L, KRAS_G13C

[0248] (28.06707317); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C, KRAS_G13D

[0249] (28.01219512); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L, KRAS_G13C

[0250] (27.94512195); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273L, KRAS_G13C

[0251] (27.93292683); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13D, EGFR_L861 Q

[0252] (27.93292683); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13C (27.92682927); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_V157F, KRAS_G13C (27.92682927);

[0253] KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M, KRAS_G13D (27.92073171);

[0254] KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C, EGFR_L861 Q (27.91463415);

[0255] KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R273L, KRAS_G13D (27.90243902); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13C, TP53_R273C (27.85365854); KRAS_G12C, KRAS_G12V,

[0256] KRAS_G12D, KRAS_G13C, TP53_R175H (27.84146341); KRAS_G12C, KRAS_G12V, KRAS_G12D,

[0257] TP53_R273L, EGFR_L861 Q (27.83536585); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D,

[0258] TP53_R158L, KRAS_G13C (27.80487805); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D,

[0259] TP53_V157F, KRAS_G13C (27.79268293); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D,

[0260] TP53_R273L, KRAS_G13D (27.7804878); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L, KRAS_G13D (27.7804878); KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M, TP53_R273L (27.77439024); KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M, EGFR_L861 Q (27.76219512); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_V157F, KRAS_G13D (27.76219512); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D, EGFR_L861 Q (27.75609756); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13D (27.73780488); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R273L (27.7195122); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L, EGFR_L861 Q (27.71341463); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_R273L (27.70731707); KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M, TP53_R158L (27.69512195); KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M, TP53_V157F (27.69512195); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273L, EGFR_L861 Q (27.68902439); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_V157F, EGFR_L861 Q (27.68902439); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_V157F, TP53_R273L (27.68902439); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13D, TP53_R273C (27.68292683); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13D, TP53_R175H (27.67682927); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_L861 Q (27.66463415); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R158L (27.66463415); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C, TP53_R175H (27.65243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R158L, KRAS_G13D (27.65243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, KRAS_G13D (27.6402439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C, TP53_R273C (27.63414634); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R158L, TP53_R273L (27.6097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V (27.6097561); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R175H, EGFR_L861 Q (27.60365854); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, TP53_R273L (27.59756098); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R273C, EGFR_L861 Q (27.59756098); KRAS_G12C, KRAS_G12V,

[0261] KRAS_G12D, TP53_R273L, TP53_R273C (27.59146341); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R273L, TP53_R175H (27.58536585); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_T790M (27.57926829); KRAS_G12C, KRAS_G12V, KRAS_G12D,

[0262] TP53_R158L, TP53_V157F (27.56707317); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R158L, EGFR_L861 Q (27.56097561); KRAS_G12C, EGFR_L858R, KRAS_G12A,

[0263] EGFR_T790M, TP53_R175H (27.56097561); KRAS_G12C, EGFR_L858R, KRAS_G12D

[0264] (27.55487805); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M (27.54268293); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, EGFR_L861 Q (27.54268293); KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M, TP53_R273C (27.54268293); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_V157F (27.5304878);

[0265] KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D, TP53_R175H (27.5); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D, TP53_R273C (27.47560976); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_R273C (27.47560976); KRAS_G12C,

[0266] EGFR_E746_A750del, KRAS_G12D, TP53_R158L, TP53_V157F (27.4695122); KRAS_G12C,

[0267] KRAS_G12V, KRAS_G12A, EGFR_T790M, KRAS_G13C (27.4695122); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_R175H (27.46341463); KRAS_G12C, KRAS_G12V, KRAS_G12D,

[0268] TP53_V157F, TP53_R273C (27.45731707); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_V157F,

[0269] TP53_R175H (27.45121951); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273L,

[0270] TP53_R175H (27.43902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273L, TP53_R273C (27.41463415); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R175H, EGFR_L861 Q (27.40243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273C,

[0271] EGFR_L861 Q (27.36585366); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D,

[0272] TP53_R273C (27.35365854); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R175H, TP53_R273C

[0273] (27.35365854); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R175H (27.32317073); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R158L, TP53_R175H (27.31097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, TP53_R175H (27.30487805); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R158L, TP53_R273C (27.29268293); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, TP53_R273C

[0274] (27.2804878); KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_T790M, KRAS_G13D (27.2804878); KRAS_G12C, EGFR_L858R, KRAS_G12A, KRAS_G13C, KRAS_G13D (27.24390244); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13C (27.23170732); KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_T790M, EGFR_L861 Q (27.17073171); KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_T790M, TP53_R273L (27.14634146); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R175H, TP53_R273C (27.12195122); KRAS_G12C, EGFR_L858R, KRAS_G12A,

[0275] KRAS_G13C, EGFR_L861 Q (27.1097561); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R273L, KRAS_G13C (27.08536585); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13D (27.06097561); KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_T790M, TP53_R158L (27.04878049); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C (27.04268293); KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_T790M, TP53_V157F (27.04268293); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_V157F, KRAS_G13C (27); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R158L, KRAS_G13C (26.99390244); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_L861 Q (26.98780488); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R273L (26.9695122); KRAS_G12C,

[0276] KRAS_G12V, KRAS_G12A, EGFR_T790M, TP53_R273C (26.95731707); KRAS_G12C,

[0277] EGFR_L858R, KRAS_G12A, EGFR_T790M (26.94512195); KRAS_G12C, EGFR_L858R,

[0278] KRAS_G12A, KRAS_G13D, EGFR_L861 Q (26.94512195); KRAS_G12C, KRAS_G12V, KRAS_G12A,

[0279] EGFR_T790M, TP53_R175H (26.94512195); KRAS_G12C, EGFR_L858R, KRAS_G12A,

[0280] TP53_R273L, KRAS_G13D (26.92682927); KRAS_G12C, EGFR_L858R, KRAS_G12A, KRAS_G13C, TP53_R175H (26.8902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D

[0281] (26.88414634); KRAS_G12C, EGFR_L858R, KRAS_G12A, KRAS_G13C, TP53_R273C

[0282] (26.87804878); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L (26.85365854);

[0283] KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_V157F, KRAS_G13D (26.84146341); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R158L, KRAS_G13D (26.83536585); KRAS_G12C, KRAS_G12V,

[0284] KRAS_G12D, TP53_V157F (26.83536585); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273L (26.82317073); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R273L,

[0285] EGFR_L861 Q (26.79878049); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_L861 Q (26.78658537); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D (26.77439024); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R273C (26.73780488); KRAS_G12C,

[0286] EGFR_L858R, KRAS_G12A, KRAS_G13D, TP53_R175H (26.73170732); KRAS_G12C, KRAS_G12V,

[0287] KRAS_G12D, TP53_R175H (26.73170732); KRAS_G12C, EGFR_L858R, KRAS_G12A,

[0288] TP53_V157F, TP53_R273L (26.7195122); KRAS_G12C, EGFR_L858R, KRAS_G12A, KRAS_G13D,

[0289] TP53_R273C (26.71341463); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R158L, TP53_R273L (26.71341463); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R158L, EGFR_L861 Q

[0290] (26.70731707); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_V157F, EGFR_L861 Q

[0291] (26.70731707); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R158L (26.70121951);

[0292] KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_V157F (26.68902439); KRAS_G12C,

[0293] EGFR_L858R, KRAS_G12A, TP53_R158L, TP53_V157F (26.62804878); KRAS_G12C,

[0294] EGFR_L858R, KRAS_G12A, TP53_R175H, EGFR_L861 Q (26.59756098); KRAS_G12C,

[0295] EGFR_L858R, KRAS_G12A, TP53_R273L, TP53_R175H (26.59146341); KRAS_G12C,

[0296] EGFR_L858R, KRAS_G12A, TP53_R273L, TP53_R273C (26.57317073); KRAS_G12C,

[0297] EGFR_L858R, KRAS_G12A, TP53_R273C, EGFR_L861 Q (26.56707317); KRAS_G12C,

[0298] EGFR_E746_A750del, KRAS_G12D, TP53_R175H (26.5304878); KRAS_G12C, EGFR_L858R,

[0299] EGFR_T790M, KRAS_G13C, KRAS_G13D (26.51219512); KRAS_G12C, EGFR_L858R,

[0300] KRAS_G12A, TP53_V157F, TP53_R175H (26.51219512); KRAS_G12C, EGFR_E746_A750del,

[0301] KRAS_G12D, TP53_R273C (26.50609756); KRAS_G12C, EGFR_L858R, KRAS_G12A,

[0302] TP53_R158L, TP53_R175H (26.50609756); KRAS_G12C, EGFR_L858R, KRAS_G12A,

[0303] TP53_V157F, TP53_R273C (26.49390244); KRAS_G12C, EGFR_L858R, KRAS_G12A,

[0304] TP53_R158L, TP53_R273C (26.48780488); KRAS_G12C, EGFR_L858R, EGFR_T790M,

[0305] TP53_R273L, KRAS_G13C (26.38414634); KRAS_G12C, EGFR_L858R, KRAS_G12A,

[0306] TP53_R175H, TP53_R273C (26.36585366); KRAS_G12C, EGFR_L858R, EGFR_T790M,

[0307] KRAS_G13C, EGFR_L861 Q (26.34756098); KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_T790M (26.33536585); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R158L, KRAS_G13C (26.28658537); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_V157F,

[0308] KRAS_G13C (26.27439024); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, KRAS_G13C (26.26219512); KRAS_G12C, EGFR_L858R, KRAS_G12A, KRAS_G13C

[0309] (26.26219512); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R273L, KRAS_G13D

[0310] (26.23170732); KRAS_G12C, EGFR_L858R, EGFR_T790M, KRAS_G13D, EGFR_L861 Q

[0311] (26.18902439); KRAS_G12C, EGFR_L858R, EGFR_T790M, KRAS_G13C, TP53_R175H

[0312] (26.15853659); KRAS_G12C, EGFR_L858R, EGFR_T790M, KRAS_G13C, TP53_R273C

[0313] (26.1402439); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R158L, KRAS_G13D

[0314] (26.13414634); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_V157F, KRAS_G13D (26.12195122); KRAS_G12C, KRAS_G12V, KRAS_G12D (26.11585366); KRAS_G12C,

[0315] EGFR_L858R, KRAS_G12A, KRAS_G13D (26.09756098); KRAS_G12C, EGFR_E746_A750del,

[0316] KRAS_G12A, EGFR_T790M, KRAS_G13D (26.09146341); KRAS_G12C, EGFR_L858R,

[0317] EGFR_T790M, TP53_R273L, EGFR_L861 Q (26.07317073); KRAS_G12C, EGFR_L858R,

[0318] EGFR_T790M, TP53_R158L, TP53_R273L (26.04268293); KRAS_G12C, EGFR_L858R,

[0319] EGFR_T790M, TP53_V157F, TP53_R273L (26.0304878); KRAS_G12C, EGFR_L858R,

[0320] EGFR_T790M, KRAS_G13D, TP53_R175H (26.00609756); KRAS_G12C, EGFR_L858R,

[0321] EGFR_T790M, KRAS_G13D, TP53_R273C (25.98170732); KRAS_G12C, EGFR_E746_A750del,

[0322] KRAS_G12A, EGFR_T790M, TP53_R273L (25.97560976); KRAS_G12C, EGFR_L858R,

[0323] EGFR_T790M, TP53_R158L, EGFR_L861 Q (25.97560976); KRAS_G12C, EGFR_L858R,

[0324] KRAS_G12A, EGFR_L861 Q (25.96341463); KRAS_G12C, EGFR_L858R, EGFR_T790M,

[0325] TP53_V157F, EGFR_L861 Q (25.95731707); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R273L

[0326] (25.95731707); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, EGFR_L861 Q

[0327] (25.95121951); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R158L, TP53_V157F

[0328] (25.93292683); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D (25.91463415); KRAS_G12C,

[0329] EGFR_L858R, EGFR_T790M, TP53_R273L, TP53_R175H (25.89634146); KRAS_G12C,

[0330] EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_V157F (25.8902439); KRAS_G12C,

[0331] EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R158L (25.88414634); KRAS_G12C,

[0332] EGFR_L858R, KRAS_G12A, TP53_V157F (25.87804878); KRAS_G12C, EGFR_L858R,

[0333] EGFR_T790M, TP53_R273L, TP53_R273C (25.87195122); KRAS_G12C, EGFR_L858R,

[0334] KRAS_G12A, TP53_R158L (25.87195122); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13C,

[0335] KRAS_G13D (25.86585366); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R175H,

[0336] EGFR_L861 Q (25.84146341); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R273C,

[0337] EGFR_L861 Q (25.80487805); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R158L,

[0338] TP53_R175H (25.79878049); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_V157F,

[0339] TP53_R175H (25.79268293); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R158L,

[0340] TP53_R273C (25.7804878); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_V157F, TP53_R273C

[0341] (25.76829268); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M, KRAS_G13C

[0342] (25.76829268); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R175H (25.75); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13C, EGFR_L861 Q (25.75); KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13C, KRAS_G13D (25.75); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273L, KRAS_G13C (25.74390244); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, TP53_R175H (25.73170732); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R273C (25.73170732); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M,

[0343] TP53_R273C (25.7195122); KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13C, EGFR_L861 Q

[0344] (25.66463415); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R175H, TP53_R273C

[0345] (25.63414634); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L, KRAS_G13C

[0346] (25.63414634); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, KRAS_G13C, KRAS_G13D

[0347] (25.61585366); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_V157F, KRAS_G13C

[0348] (25.61585366); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R273L, KRAS_G13C

[0349] (25.60365854); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M, KRAS_G13D

[0350] (25.59756098); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13D, EGFR_L861 Q

[0351] (25.57317073); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273L, KRAS_G13D

[0352] (25.57317073); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13C, TP53_R273C

[0353] (25.54878049); KRAS_G12C, EGFR_L858R, TP53_R273L, KRAS_G13C, KRAS_G13D

[0354] (25.53658537); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13C, TP53_R175H

[0355] (25.53658537); KRAS_G12C, EGFR_L858R, KRAS_G13C, KRAS_G13D, EGFR_L861 Q

[0356] (25.5304878); KRAS_G12C, EGFR_L858R, EGFR_T790M, KRAS_G13C (25.52439024);

[0357] KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, KRAS_G13C, EGFR_L861Q (25.50609756);

[0358] KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M, TP53_R273L (25.50609756); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_V157F, KRAS_G13C (25.50609756); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, KRAS_G13C (25.5); KRAS_G12C, KRAS_G12V,

[0359] KRAS_G12A, TP53_R158L, KRAS_G13C (25.5); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R273L, KRAS_G13C (25.49390244); KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13D,

[0360] EGFR_L861 Q (25.48170732); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M,

[0361] EGFR_L861 Q (25.47560976); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L,

[0362] KRAS_G13D (25.46341463); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273L,

[0363] EGFR_L861 Q (25.46341463); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_V157F,

[0364] KRAS_G13D (25.44512195); KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13C, TP53_R273C

[0365] (25.43902439); KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13C, TP53_R175H

[0366] (25.43292683); KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13C, KRAS_G13D

[0367] (25.42682927); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R273L, KRAS_G13D

[0368] (25.42682927); KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13C, KRAS_G13D

[0369] (25.42073171); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_V157F, KRAS_G13C

[0370] (25.40243902); KRAS_G12C, EGFR_L858R, TP53_R273L, KRAS_G13C, EGFR_L861 Q

[0371] (25.40243902); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M, TP53_R158L

[0372] (25.40243902); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M, TP53_V157F

[0373] (25.39634146); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R158L, KRAS_G13C

[0374] (25.3902439); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L, TP53_R273L

[0375] (25.37804878); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13D, TP53_R273C

[0376] (25.37195122); KRAS_G12C, EGFR_L858R, EGFR_T790M, KRAS_G13D (25.36585366);

[0377] KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13D, TP53_R175H (25.36585366);

[0378] KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_V157F, TP53_R273L (25.3597561); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L, EGFR_L861 Q (25.35365854); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R273L, EGFR_L861 Q (25.34756098); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, KRAS_G13D, EGFR_L861 Q (25.33536585); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R273L, KRAS_G13D (25.32926829); KRAS_G12C, EGFR_L858R, KRAS_G13C, KRAS_G13D, TP53_R175H (25.32926829); KRAS_G12C,

[0379] KRAS_G12V, EGFR_T790M, TP53_V157F, EGFR_L861 Q (25.32926829); KRAS_G12C,

[0380] KRAS_G12V, KRAS_G12A, TP53_V157F, KRAS_G13D (25.32926829); KRAS_G12C, EGFR_L858R,

[0381] TP53_R158L, TP53_R273L, KRAS_G13C (25.32317073); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L, KRAS_G13D (25.32317073); KRAS_G12C, EGFR_L858R, TP53_V157F, TP53_R273L,

[0382] KRAS_G13C (25.31707317); KRAS_G12C, EGFR_L858R, KRAS_G13C, KRAS_G13D, TP53_R273C

[0383] (25.31097561); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, KRAS_G13D

[0384] (25.29268293); KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13C, EGFR_L861 Q

[0385] (25.29268293); KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13C, EGFR_L861 Q

[0386] (25.2804878); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, KRAS_G13C, TP53_R175H

[0387] (25.26829268); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273L, TP53_R273C

[0388] (25.26829268); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M, TP53_R175H

[0389] (25.26219512); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M, TP53_R273C

[0390] (25.26219512); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273L, TP53_R175H

[0391] (25.26219512); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R273L (25.25609756);

[0392] KRAS_G12C, EGFR_L858R, TP53_R273L, KRAS_G13D, EGFR_L861 Q (25.25609756);

[0393] KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13D, TP53_R175H (25.25609756); KRAS_G12C,

[0394] KRAS_G12V, KRAS_G12A, KRAS_G13D, TP53_R273C (25.25609756); KRAS_G12C,

[0395] EGFR_E746_A750del, KRAS_G12A, KRAS_G13C, TP53_R273C (25.25); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L, TP53_V157F (25.25); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R175H, EGFR_L861 Q (25.25); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273C, EGFR_L861 Q (25.24390244); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L, EGFR_L861 Q (25.24390244); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_V157F, EGFR_L861 Q (25.24390244); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_V157F,

[0396] KRAS_G13D (25.23780488); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A,

[0397] TP53_R273L (25.23170732); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R158L,

[0398] KRAS_G13D (25.22560976); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R273L,

[0399] EGFR_L861 Q (25.22560976); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_V157F, TP53_R273L (25.2195122); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L, TP53_R273L (25.21341463);

[0400] KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F, KRAS_G13C (25.20731707); KRAS_G12C,

[0401] EGFR_L858R, TP53_R273L, KRAS_G13C, TP53_R175H (25.20731707); EGFR_L858R,

[0402] EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, EGFR_L861 Q (25.20121951); EGFR_L858R,

[0403] EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, TP53_R158L (25.20121951); KRAS_G12C,

[0404] EGFR_L858R, EGFR_T790M, EGFR_L861 Q (25.20121951); KRAS_G12C, EGFR_L858R,

[0405] KRAS_G13C, TP53_R175H, EGFR_L861 Q (25.18902439); KRAS_G12C, EGFR_L858R,

[0406] TP53_R273L, KRAS_G13C, TP53_R273C (25.18902439); KRAS_G12C, EGFR_L858R,

[0407] TP53_R158L, TP53_R273L, KRAS_G13D (25.18292683); KRAS_G12C, EGFR_L858R, TP53_V157F,

[0408] TP53_R273L, KRAS_G13D (25.17682927); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R175H,

[0409] EGFR_L861 Q (25.17073171); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R158L (25.16463415); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L, TP53_R273C (25.16463415); KRAS_G12C, EGFR_L858R, KRAS_G13C, TP53_R273C, EGFR_L861 Q (25.15853659); KRAS_G12C, KRAS G12V, KRAS G12A, TP53 R273C, EGFR L861 Q

[0410] (25.15853659); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_V157F, TP53_R273L

[0411] (25.15243902); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_V157F (25.15243902);

[0412] KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L, TP53_R175H (25.15243902);

[0413] KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13D, EGFR_L861 Q (25.14634146);

[0414] KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_V157F, TP53_R273C (25.14634146);

[0415] KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R158L, TP53_R273L (25.1402439);

[0416] KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_V157F, TP53_R175H (25.1402439); KRAS_G12C,

[0417] EGFR_L858R, TP53_V157F, KRAS_G13D, EGFR_L861 Q (25.13414634); KRAS_G12C,

[0418] EGFR_E746_A750del, KRAS_G12A, TP53_V157F, EGFR_L861 Q (25.12804878); KRAS_G12C,

[0419] KRAS_G12V, KRAS_G12A, TP53_R273L, TP53_R175H (25.12804878); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R273L, TP53_R273C (25.12804878); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R158L, EGFR_L861 Q (25.12195122); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, EGFR_T790M (25.11585366); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M (25.11585366); KRAS_G12C, EGFR_L858R, KRAS_G12A (25.11585366); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L, TP53_V157F (25.11585366);

[0420] KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, KRAS_G13D, TP53_R175H (25.10365854);

[0421] EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, TP53_V157F (25.09756098);

[0422] KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13C, TP53_R175H (25.09756098);

[0423] KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13C, TP53_R175H (25.09756098);

[0424] KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13C, TP53_R273C (25.08536585);

[0425] KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, KRAS_G13D, TP53_R273C (25.07926829);

[0426] KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13C, TP53_R273C (25.07926829);

[0427] KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F, KRAS_G13D (25.06707317); KRAS_G12C,

[0428] EGFR_L858R, TP53_R273L, KRAS_G13D, TP53_R175H (25.06707317); KRAS_G12C,

[0429] EGFR_L858R, TP53_R158L, TP53_R273L, EGFR_L861 Q (25.05487805); KRAS_G12C,

[0430] EGFR_E746_A750del, KRAS_G12A, TP53_R158L, TP53_V157F (25.04878049); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R175H, TP53_R273C (25.04878049); KRAS_G12C,

[0431] EGFR_L858R, KRAS_G13D, TP53_R175H, EGFR_L861 Q (25.04268293); KRAS_G12C,

[0432] EGFR_L858R, TP53_R273L, KRAS_G13D, TP53_R273C (25.04268293); KRAS_G12C,

[0433] EGFR_L858R, TP53_V157F, TP53_R273L, EGFR_L861 Q (25.04268293); KRAS_G12C,

[0434] KRAS_G12V, KRAS_G12A, TP53_V157F, TP53_R175H (25.03658537); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_V157F, TP53_R273C (25.03658537); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L, TP53_R175H (25.0304878); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L, TP53_R273C (25.0304878); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R175H

[0435] (25.01829268); KRAS_G12C, EGFR_L858R, KRAS_G13D, TP53_R273C, EGFR L861 Q

[0436] (25.00609756); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R273L, TP53_R175H (25); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F, TP53_R273L (25); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R175H, EGFR_L861 Q (24.99390244); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R273C (24.99390244); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R273L, TP53_R273C (24.97560976); KRAS_G12C, EGFR_L858R, KRAS_G13C, TP53_R175H, TP53_R273C (24.9695122); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R273C, EGFR_L861 Q (24.95731707); KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13D, TP53_R175H (24.95731707); KRAS_G12C, EGFR_L858R,

[0437] TP53_V157F, KRAS_G13D, TP53_R175H (24.95731707); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R175H, TP53_R273C (24.94512195); KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13D, TP53_R273C (24.93902439); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F, EGFR_L861 Q (24.93292683); KRAS_G12C, EGFR_L858R, TP53_R273L, TP53_R175H, EGFR_L861 Q (24.93292683); KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13D, TP53_R273C (24.93292683); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, TP53_R273C (24.92073171); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A,

[0438] TP53_V157F, TP53_R175H (24.91463415); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13C (24.90853659); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R158L, TP53_R175H (24.90243902); KRAS_G12C, EGFR_L858R, TP53_R273L, TP53_R273C, EGFR_L861 Q (24.89634146); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, , TP53_R175H (24.8902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_V157F, TP53_R273C (24.8902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R158L, TP53_R273C (24.87804878); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_R273L, TP53_R175H (24.87195122); KRAS_G12C, EGFR_L858R, TP53_V157F, TP53_R273L, TP53_R175H (24.87195122); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_R273L, TP53_R273C (24.85365854); KRAS_G12C, EGFR_L858R, TP53_V157F, TP53_R273L, TP53_R273C (24.84756098); KRAS_G12C, EGFR_L858R, KRAS_G13D, TP53_R175H, TP53_R273C (24.82317073); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_R175H, EGFR_L861 Q (24.82317073); KRAS_G12C, EGFR_L858R, TP53_V157F, TP53_R175H, EGFR_L861 Q (24.81707317); KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13C (24.79878049); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_R273C, EGFR_L861 Q (24.79268293); KRAS_G12C, EGFR_L858R, TP53_V157F, TP53_R273C, EGFR_L861 Q (24.7804878); EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G12A, EGFR_T790M (24.77439024); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F, TP53_R175H (24.76219512); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F, TP53 R273C (24.74390244); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R175H, TP53_R273C (24.73780488); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13D (24.73170732); KRAS_G12C, EGFR_L858R, TP53_R273L, TP53_R175H, TP53_R273C (24.7195122); KRAS_G12C, EGFR_L858R, KRAS_G13C, KRAS G13D (24.67682927); KRAS_G12C, EGFR_L858R, TP53_R175H, TP53_R273C, EGFR_L861 Q (24.67073171); KRAS_G12C, EGFR_E746_A750del,

[0439] EGFR_T790M, KRAS_G13C, KRAS_G13D (24.65853659); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, KRAS_G13C (24.6402439); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M (24.6402439); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273L (24.62804878);

[0440] KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_R175H, TP53_R273C (24.61585366); KRAS_G12C, EGFR_L858R, TP53_V157F, TP53_R175H, TP53_R273C (24.61585366); KRAS_G12C, KRAS_G12V, EGFR_T790M, EGFR L861 Q (24.61585366); KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13D (24.61585366); KRAS_G12C, EGFR_E746_A750del, EGFR T790M, TP53 R273L, KRAS G13C (24.56097561); KRAS G12C, EGFR L858R,

[0441] TP53_R273L, KRAS_G13C (24.55487805); KRAS_G12C, EGFR_L858R, KRAS_G13C, EGFR_L861 Q (24.53658537); KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_L861 Q (24.5304878); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L (24.52439024);

[0442] KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, KRAS_G13C, EGFR_L861 Q (24.51219512);

[0443] KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_V157F (24.50609756); KRAS_G12C, KRAS_G12V,

[0444] KRAS_G12A, TP53_R273L (24.48780488); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, KRAS_G13D (24.4695122); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R158L, KRAS_G13C (24.45121951); KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13C (24.45121951); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_V157F, KRAS_G13C

[0445] (24.44512195); KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13C (24.44512195); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273C (24.41463415); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R273L, KRAS_G13D (24.40853659); KRAS_G12C, EGFR_L858R, TP53_R273L, KRAS_G13D (24.40853659); KRAS_G12C, KRAS_G12V,

[0446] EGFR_T790M, TP53_R175H (24.40853659); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_V157F (24.39634146); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L (24.3902439); KRAS_G12C, EGFR_L858R, KRAS_G13D, EGFR_L861 Q (24.38414634); KRAS_G12C, EGFR_L858R, EGFR_T790M (24.37804878); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R273L (24.36585366); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, EGFR_L861 Q (24.3597561); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, KRAS_G13D, EGFR_L861 Q (24.35365854); KRAS_G12C, EGFR_L858R, KRAS_G13C, TP53_R175H (24.33536585); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A (24.32317073); KRAS_G12C, EGFR_L858R, KRAS_G13C, TP53_R273C (24.31707317); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, KRAS_G13C, TP53_R175H (24.30487805); KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13D (24.30487805); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R175H (24.30487805);

[0447] KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R273C (24.30487805); KRAS_G12C,

[0448] EGFR_E746_A750del, EGFR_T790M, TP53_R158L, KRAS_G13D (24.29878049); KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13D (24.29878049); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, KRAS_G13C, TP53_R273C (24.29268293); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_V157F, KRAS_G13D (24.29268293); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_V157F (24.2804878); KRAS_G12C, EGFR_L858R, TP53_R273L, EGFR_L861 Q (24.27439024); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R273L, EGFR_L861 Q (24.26829268); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R158L (24.26829268); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R158L, TP53_R273L (24.23780488); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_V157F, TP53_R273L (24.23170732); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_R273L (24.2195122); KRAS_G12C, EGFR_L858R, TP53_V157F, TP53_R273L (24.21341463); KRAS_G12C, EGFR_L858R, KRAS_G13D, TP53_R175H (24.18902439); KRAS_G12C, KRAS_G12D, EGFR_T790M, KRAS_G13C, KRAS_G13D

[0449] (24.18902439); KRAS_G12C, EGFR_L858R, TP53_R158L, EGFR_L861 Q (24.17073171);

[0450] KRAS_G12C, EGFR_L858R, KRAS_G13D, TP53_R273C (24.16463415); KRAS_G12C,

[0451] EGFR_E746_A750del, EGFR_T790M, TP53_R158L, EGFR_L861 Q (24.15853659); KRAS_G12C, EGFR_L858R, TP53_V157F, EGFR_L861 Q (24.15853659); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, KRAS_G13D, TP53_R175H (24.15243902); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_V157F, EGFR_L861 Q (24.14634146); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, KRAS_G13D, TP53_R273C (24.13414634); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R175H (24.12804878); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R158L, TP53_V157F (24.12195122); KRAS_G12C, KRAS_G12D, EGFR_T790M,

[0452] TP53_R273L, KRAS_G13C (24.11585366); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F (24.1097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R273C (24.10365854); EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G12A, KRAS_G13C (24.09756098); KRAS_G12C, EGFR_L858R, TP53_R273L, TP53_R175H (24.08536585); KRAS_G12C, EGFR_E746_A750del,

[0453] EGFR_T790M, TP53_R273L, TP53_R175H (24.07317073); KRAS_G12C, KRAS_G12D,

[0454] KRAS_G12A, KRAS_G13C, KRAS_G13D (24.07317073); KRAS_G12C, EGFR_L858R, TP53_R273L, TP53_R273C (24.06097561); KRAS_G12C, KRAS_G12D, EGFR_T790M, KRAS_G13C,

[0455] EGFR_L861 Q (24.06097561); KRAS_G12C, KRAS_G12V, KRAS_G13C, KRAS_G13D,

[0456] EGFR_L861 Q (24.06097561); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R273L, TP53_R273C (24.05487805); KRAS_G12C, EGFR_L858R, TP53_R175H, EGFR_L861 Q

[0457] (24.04878049); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13C, KRAS_G13D

[0458] (24.02439024); KRAS_G12C, EGFR_L858R, TP53_R273C, EGFR_L861 Q (24.01219512);

[0459] KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R175H, EGFR_L861 Q (24.00609756); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R158L, KRAS_G13C (23.99390244);

[0460] KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_R175H (23.98170732); KRAS_G12C,

[0461] EGFR_L858R, TP53_V157F, TP53_R175H (23.98170732); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R273C, EGFR_L861 Q (23.97560976); KRAS_G12C, KRAS_G12D,

[0462] EGFR_T790M, TP53_V157F, KRAS_G13C (23.97560976); KRAS_G12C, KRAS_G12D,

[0463] KRAS_G12A, KRAS_G13C, EGFR_L861 Q (23.97560976); KRAS_G12C, KRAS_G12D, KRAS_G12A,

[0464] TP53_R273L, KRAS_G13C (23.9695122); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M,

[0465] TP53_R158L, TP53_R175H (23.96341463); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M,

[0466] TP53_V157F, TP53_R175H (23.96341463); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_R273C (23.96341463); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R273L, KRAS_G13D (23.96341463); KRAS_G12C, EGFR_L858R, TP53_V157F, TP53_R273C (23.95731707); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R158L, TP53_R273C (23.95121951); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_V157F, TP53_R273C (23.94512195); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13C, EGFR_L861 Q (23.93902439); KRAS_G12C,

[0467] EGFR_E746_A750del, TP53_R273L, KRAS_G13C, KRAS_G13D (23.91463415); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13C, KRAS_G13D (23.90853659); EGFR_L858R, KRAS_G12V,

[0468] KRAS_G12D, KRAS_G12A, KRAS_G13D (23.90243902); KRAS_G12C, KRAS_G12D,

[0469] EGFR_T790M, KRAS_G13D, EGFR_L861 Q (23.90243902); KRAS_G12C, KRAS_G12V,

[0470] TP53_V157F, KRAS_G13C, KRAS_G13D (23.90243902); KRAS_G12C, EGFR_E746_A750del,

[0471] KRAS_G13C, KRAS_G13D, EGFR_L861 Q (23.89634146); KRAS_G12C, KRAS_G12D,

[0472] KRAS_G12A, TP53_V157F, KRAS_G13C (23.86585366); KRAS_G12C, KRAS_G12D,

[0473] EGFR T790M, KRAS_G13C, TP53_R175H (23.8597561); KRAS_G12C, KRAS_G12D,

[0474] EGFR_T790M, KRAS_G13C, TP53_R273C (23.8597561); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R158L, KRAS_G13C (23.8597561); EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G12A,

[0475] TP53_R273L (23.85365854); KRAS_G12C, KRAS_G12V, KRAS_G13C, KRAS_G13D, TP53_R175H

[0476] (23.84756098); KRAS_G12C, KRAS_G12V, KRAS_G13C, KRAS_G13D, TP53_R273C

[0477] (23.84756098); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R158L, KRAS_G13D

[0478] (23.84146341); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R273L, EGFR_L861 Q

[0479] (23.84146341); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C, KRAS_G13D

[0480] (23.82926829); KRAS_G12C, EGFR_L858R, TP53_R175H, TP53_R273C (23.82926829);

[0481] EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G12A, EGFR_L861 Q (23.82317073);

[0482] KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_V157F, KRAS_G13D (23.82317073);

[0483] KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13C, EGFR_L861 Q (23.82317073);

[0484] EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R158L (23.81707317); KRAS_G12C,

[0485] KRAS_G12D, KRAS_G12A, KRAS_G13D, EGFR_L861 Q (23.81097561); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R273L, KRAS_G13D (23.81097561); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273L, KRAS_G13C (23.81097561); KRAS_G12C, KRAS_G12V, TP53_V157F, KRAS_G13C, EGFR_L861 Q (23.81097561); KRAS_G12C, EGFR_E746_A750del, TP53_R273L, KRAS_G13C, EGFR_L861 Q (23.80487805); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R158L, TP53_R273L (23.80487805); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R273L, KRAS_G13C (23.80487805); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, KRAS_G13C,

[0486] KRAS_G13D (23.79268293); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, KRAS_G13C,

[0487] KRAS_G13D (23.79268293); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R273L,

[0488] KRAS_G13C (23.78658537); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R175H,

[0489] TP53_R273C (23.78658537); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_V157F, TP53_R273L (23.78658537); KRAS_G12C, KRAS_G12V, EGFR_T790M (23.77439024); KRAS_G12C,

[0490] KRAS_G12V, TP53_R273L, KRAS_G13D, EGFR_L861 Q (23.77439024); KRAS_G12C, KRAS_G12D,

[0491] KRAS_G12A, KRAS_G13C, TP53_R175H (23.75609756); KRAS_G12C, KRAS_G12V, KRAS_G13C,

[0492] TP53_R175H, EGFR_L861Q (23.75609756); KRAS_G12C, KRAS_G12D, KRAS_G12A, KRAS_G13C, TP53_R273C (23.75); KRAS_G12C, KRAS_G12V, KRAS_G13C, TP53_R273C, EGFR_L861 Q (23.74390244); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C, EGFR_L861 Q (23.73780488); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R158L,

[0493] KRAS_G13C (23.73780488); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13C, TP53_R175H (23.73170732); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13C, TP53_R273C (23.73170732); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_R273L, KRAS_G13C (23.72560976); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, TP53_R273L, KRAS_G13C (23.72560976); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R158L, EGFR_L861 Q (23.7195122); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R273L, EGFR_L861 Q (23.7195122);

[0494] EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, KRAS_G13C (23.71341463);

[0495] EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_V157F (23.70731707); KRAS_G12C,

[0496] KRAS_G12D, EGFR_T790M, KRAS_G13D, TP53_R175H (23.70731707); KRAS_G12C,

[0497] KRAS_G12D, KRAS_G12A, TP53_V157F, KRAS_G13D (23.70731707); KRAS_G12C, KRAS_G12D,

[0498] EGFR_T790M, KRAS_G13D, TP53_R273C (23.70121951); KRAS_G12C, KRAS_G12D,

[0499] KRAS_G12A, TP53_R158L, KRAS_G13D (23.70121951); KRAS_G12C, KRAS_G12D,

[0500] EGFR_T790M, TP53_V157F, EGFR_L861 Q (23.69512195); KRAS_G 12C , KRAS_G 12 V,

[0501] TP53_R158L, TP53_V157F, KRAS_G13C (23.68902439); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, KRAS_G13C, EGFR_L861 Q (23.68292683); KRAS_G12C, EGFR_L858R, KRAS_G13C (23.68292683); KRAS_G12C, EGFR_E746_A750del, KRAS_G13C, KRAS_G13D, TP53_R175H (23.67682927); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, KRAS_G13C, EGFR_L861 Q (23.67682927); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, KRAS_G13C (23.67073171); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R158L, TP53_V157F

[0502] (23.66463415); KRAS_G12C, KRAS_G12V, KRAS_G12A (23.66463415); KRAS_G12C, KRAS_G12V,

[0503] TP53_R158L, KRAS_G13D, EGFR_L861 Q (23.65853659); EGFR_L858R, EGFR_E746_A750del,

[0504] KRAS_G12V, EGFR_T790M, KRAS_G13C (23.65243902); KRAS_G12C, EGFR_E746_A750del,

[0505] KRAS_G13C, KRAS_G13D, TP53_R273C (23.65243902); KRAS_G12C, EGFR_E746_A750del,

[0506] TP53_R273L, KRAS_G13D, EGFR_L861 Q (23.65243902); KRAS_G12C, KRAS_G12D,

[0507] EGFR_T790M, TP53_R273L, TP53_R175H (23.65243902); KRAS_G12C, KRAS_G12V,

[0508] TP53_R158L, TP53_R273L, KRAS_G13D (23.65243902); KRAS_G12C, KRAS_G12D,

[0509] EGFR_T790M, TP53_R273L, TP53_R273C (23.64634146); KRAS_G12C, KRAS_G12V,

[0510] TP53_V157F, KRAS_G13D, EGFR_L861 Q (23.64634146); KRAS_G12C, KRAS_G12V, TP53_V157F,

[0511] TP53_R273L, KRAS_G13D (23.64634146); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_V157F, TP53_R273L (23.6402439); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R158L, TP53_R273L

[0512] (23.63414634); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, KRAS_G13C

[0513] (23.62195122); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13C, TP53_R273C

[0514] (23.62195122); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13C, TP53_R175H

[0515] (23.61585366); KRAS_G12C, KRAS_G12V, TP53_V157F, KRAS_G13C, TP53_R175H

[0516] (23.61585366); KRAS_G12C, KRAS_G12V, TP53_V157F, KRAS_G13C, TP53_R273C

[0517] (23.61585366); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R158L, EGFR_L861 Q

[0518] (23.6097561); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_V157F, EGFR_L861 Q (23.6097561);

[0519] KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_V157F, KRAS_G13C (23.60365854); EGFR L858R, EGFR E746 A750del, KRAS G12V, TP53 R273L, KRAS G13D (23.59756098);

[0520] KRAS_G12C, KRAS_G12D, KRAS_G12A, KRAS_G13D, TP53_R175H (23.59756098); KRAS_G12C, EGFR_E746_A750del, TP53_R273L, KRAS_G13C, TP53_R175H (23.59146341); KRAS_G12C, KRAS_G12V, KRAS_G13D, TP53_R175H, EGFR_L861 Q (23.59146341); KRAS_G12C,

[0521] KRAS_G12D, KRAS_G12A, KRAS_G13D, TP53_R273C (23.58536585); KRAS_G12C,

[0522] EGFR_E746_A750del, TP53_R158L, TP53_R273L, KRAS_G13D (23.57926829); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, TP53_R273L, KRAS_G13D (23.57926829); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R175H, EGFR_L861 Q (23.57926829); EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R273C (23.57317073); KRAS_G12C, KRAS_G12V, KRAS_G13D, TP53_R273C, EGFR_L861 Q (23.57317073); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273L, EGFR_L861 Q (23.57317073); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13D, TP53_R175H (23.57317073); KRAS_G12C, EGFR_E746_A750del, TP53_R273L, KRAS_G13C, TP53_R273C (23.56707317); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13D, TP53_R273C (23.56707317); KRAS_G12C, EGFR_E746_A750del, KRAS_G13C, TP53_R175H, EGFR_L861 Q (23.56097561); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R273C, EGFR_L861 Q (23.56097561); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R273L, EGFR_L861 Q (23.56097561); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, KRAS_G13D (23.55487805); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, TP53_R273L (23.54878049); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13D, EGFR_L861 Q (23.54268293); KRAS_G12C, KRAS_G12V, KRAS_G13C, TP53_R175H, TP53_R273C

[0523] (23.54268293); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, KRAS_G13D (23.53658537); EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R175H

[0524] (23.5304878); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, KRAS_G13D, EGFR_L861 Q (23.5304878); KRAS_G12C, EGFR_L858R, KRAS_G13D (23.5304878); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R158L, TP53_R175H (23.5304878); KRAS_G12C, KRAS_G12D,

[0525] EGFR_T790M, TP53_R158L, TP53_R273C (23.5304878); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R158L, TP53_V157F (23.5304878); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_V157F, KRAS_G13D (23.5304878); KRAS_G12C, EGFR_E746_A750del, KRAS_G13C, TP53_R273C, EGFR_L861 Q (23.52439024); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, KRAS_G13D, EGFR_L861 Q (23.52439024); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_V157F, TP53_R175H (23.51829268); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R273L, EGFR_L861 Q (23.51219512); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, KRAS_G13D (23.51219512); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_V157F, TP53_R273C

[0526] (23.51219512); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R273L, TP53_R175H

[0527] (23.51219512); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_R273L (23.50609756); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R175H, EGFR_L861 Q (23.5); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R273L, TP53_R273C (23.5); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A (23.49390244); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_R158L (23.48780488); KRAS_G12C, KRAS_G12V, TP53_R273L, TP53_R175H, EGFR_L861 Q (23.48780488); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_R273L, EGFR_L861 Q (23.47560976); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, KRAS_G13C, TP53_R175H (23.47560976); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R273C, EGFR_L861 Q (23.47560976); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, KRAS_G13C, TP53_R175H (23.4695122); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, TP53_R273L, EGFR_L861 Q (23.4695122); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_V157F, TP53_R273L (23.4695122); KRAS_G12C, KRAS_G12V, TP53_R273L, TP53_R273C, EGFR_L861 Q (23.4695122); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C, TP53_R273C (23.46341463); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, EGFR_L861 Q (23.46341463); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, KRAS_G13D (23.45731707); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_V157F, KRAS_G13D (23.45731707); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13D, TP53_R175H (23.45731707); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13D, TP53_R273C (23.45731707); KRAS_G12C, KRAS_G12V,

[0528] TP53_V157F, KRAS_G13D, TP53_R175H (23.45731707); KRAS_G12C, EGFR_E746_A750del,

[0529] TP53_R158L, KRAS_G13C, TP53_R273C (23.45121951); KRAS_G12C, EGFR_E746_A750del,

[0530] TP53_V157F, KRAS_G13C, TP53_R273C (23.45121951); KRAS_G12C, KRAS_G12V, TP53_V157F,

[0531] KRAS_G13D, TP53_R273C (23.45121951); KRAS_G12C, EGFR_E746_A750del, TP53_R273L,

[0532] KRAS_G13D, TP53_R175H (23.44512195); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_V157F, EGFR_L861 Q (23.44512195); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C, TP53_R175H (23.43292683); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, KRAS_G13D (23.43292683); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R273L (23.43292683); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, EGFR_L861 Q

[0533] (23.42682927); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, TP53_R273L

[0534] (23.42682927); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_V157F, TP53_R273L

[0535] (23.42682927); KRAS_G12C, EGFR_L858R, TP53_R273L (23.42682927); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_R273L (23.42073171); KRAS_G12C, EGFR_E746_A750del, TP53_R273L, KRAS_G13D, TP53_R273C (23.41463415); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_V157F, TP53_R175H (23.41463415); KRAS_G12C,

[0536] EGFR_E746_A750del, KRAS_G13D, TP53_R175H, EGFR_L861 Q (23.40853659); KRAS_G12C,

[0537] KRAS_G12D, KRAS_G12A, TP53_R158L, TP53_R175H (23.40853659); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_V157F, TP53_R273C (23.40243902); EGFR_L858R, EGFR_E746_A750del,

[0538] KRAS_G12V, EGFR_T790M, TP53_R158L (23.39634146); KRAS_G12C, KRAS_G12D, KRAS_G12A,

[0539] TP53_R158L, TP53_R273C (23.39634146); KRAS_G12C, EGFR_L858R, EGFR_L861 Q

[0540] (23.3902439); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, TP53_V157F

[0541] (23.38414634); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R175H, TP53_R273C

[0542] (23.37804878); KRAS_G12C, KRAS_G12V, KRAS_G13D, TP53_R175H, TP53_R273C

[0543] (23.37804878); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273L, TP53_R175H

[0544] (23.37804878); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273L, TP53_R273C

[0545] (23.37804878); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R273L, TP53_R175H

[0546] (23.37804878); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R175H, EGFR_L861 Q

[0547] (23.37195122); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R273L, TP53_R273C

[0548] (23.37195122); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_V157F

[0549] (23.36585366); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, EGFR_L861 Q (23.36585366);

[0550] KRAS_G12C, EGFR_E746_A750del, KRAS_G13D, TP53_R273C, EGFR_L861 Q (23.36585366);

[0551] KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R175H, EGFR_L861 Q (23.36585366); KRAS_G12C,

[0552] KRAS_G12V, TP53_R158L, TP53_R273C, EGFR_L861 Q (23.3597561); KRAS_G12C,

[0553] EGFR_E746_A750del, TP53_R158L, TP53_V157F, EGFR_L861 Q (23.34756098); KRAS_G12C,

[0554] KRAS_G12V, TP53_V157F, TP53_R273C, EGFR_L861 Q (23.34756098); EGFR_L858R,

[0555] EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, EGFR_T790M (23.34146341); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, EGFR_L861 Q (23.34146341); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, EGFR_L861 Q (23.33536585); KRAS_G12C, EGFR_E746_A750del, TP53_R273L, TP53_R175H, EGFR_L861 Q (23.33536585); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R158L (23.32926829); KRAS_G12C,

[0556] EGFR_E746_A750del, TP53_V157F, KRAS_G13D, TP53_R175H (23.32926829); KRAS_G12C,

[0557] EGFR_L858R, TP53_R158L (23.32926829); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M,

[0558] TP53_V157F (23.32317073); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, KRAS_G13D,

[0559] TP53_R175H (23.32317073); KRAS_G12C, EGFR_L858R, TP53_V157F (23.32317073);

[0560] EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_T790M, KRAS_G13C (23.31707317);

[0561] KRAS_G12C, EGFR_E746_A750del, KRAS_G13C, TP53_R175H, TP53_R273C (23.31707317);

[0562] KRAS_G12C, EGFR_E746_A750del, TP53_R158L, KRAS_G13D, TP53_R273C (23.29878049);

[0563] KRAS_G12C, EGFR_E746_A750del, TP53_V157F, KRAS_G13D, TP53_R273C (23.29878049); KRAS_G12C, EGFR_E746_A750del, TP53_R273L, TP53_R273C, EGFR_L861Q (23.29268293);

[0564] KRAS_G12C, EGFR_E746_A750del, TP53_V157F, TP53_R273L, TP53_R175H (23.2804878);

[0565] KRAS_G12C, KRAS_G12V, TP53_R273L, TP53_R175H, TP53_R273C (23.2804878); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_V157F (23.27439024); KRAS_G12C,

[0566] EGFR_E746_A750del, TP53_R158L, TP53_R273L, TP53_R175H (23.27439024); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R175H, TP53_R273C (23.27439024); KRAS_G12C, KRAS_G12V,

[0567] TP53_R175H, TP53_R273C, EGFR_L861Q (23.27439024); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13D, TP53_R273C (23.26829268); KRAS_G12C, KRAS_G12V, TP53_R158L,

[0568] TP53_V157F, TP53_R175H (23.26219512); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_V157F,

[0569] TP53_R273C (23.26219512); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_R273L,

[0570] TP53_R273C (23.25); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, TP53_R273L,

[0571] TP53_R273C (23.25); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13D,

[0572] TP53_R175H (23.24390244); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R273L, TP53_R273C (23.24390244); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R273L,

[0573] TP53_R175H (23.2195122); KRAS_G12C, KRAS_G12D, EGFR_T790M, KRAS_G13C (23.2195122);

[0574] KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_R175H, EGFR_L861Q (23.21341463); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, TP53_R175H, EGFR_L861Q (23.21341463); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, TP53_R273C (23.20731707); KRAS_G12C, EGFR_L858R, TP53_R175H (23.19512195); KRAS_G12C, KRAS_G12V,

[0575] KRAS_G13C, KRAS_G13D (23.18902439); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, TP53_R175H (23.17682927); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_R273C, EGFR_L861Q (23.17682927); KRAS_G12C, EGFR_E746_A750del, TP53_V157F,

[0576] TP53_R273C, EGFR_L861Q (23.17073171); KRAS_G12C, EGFR_L858R, TP53_R273C

[0577] (23.17073171); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R175H, TP53_R273C

[0578] (23.17073171); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R175H, TP53_R273C

[0579] (23.17073171); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R273C, EGFR_L861Q

[0580] (23.16463415); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R175H (23.16463415); KRAS_G12C, EGFR_E746_A750del, KRAS_G13D, TP53_R175H, TP53_R273C (23.16463415); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_V157F, TP53_R175H (23.15853659); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R175H, EGFR_L861Q (23.15243902); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_R273C (23.14634146); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M, TP53_R273C (23.14634146); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_R175H (23.13414634); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_V157F, TP53_R273C (23.13414634); EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_T790M, KRAS_G13D (23.12804878); EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R273L (23.1097561); KRAS_G12C, KRAS_G12D, KRAS_G12A, KRAS_G13C (23.1097561); KRAS_G12C, EGFR_E746_A750del, TP53_R273L, TP53_R175H, TP53_R273C (23.09756098); KRAS_G12C, KRAS_G12V, KRAS_G13C, EGFR_L861Q (23.09756098); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_R273C (23.08536585); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, TP53_R273C (23.08536585); EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R158L (23.07317073); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13C (23.07317073); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_R175H (23.06097561); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, TP53_R175H (23.06097561); KRAS_G12C, KRAS_G12D, EGFR_T790M, KRAS_G13D (23.06097561); KRAS_G12C,

[0581] EGFR_E746_A750del, TP53_R175H, TP53_R273C, EGFR_L861Q (23.03658537); EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_T790M, EGFR_L861Q (23.02439024); KRAS_G12C,

[0582] EGFR_E746_A750del, KRAS_G13C, KRAS_G13D (23.02439024); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R273L (23.00609756); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, TP53_R175H, TP53_R273C (22.98780488); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_R175H, TP53_R273C (22.98170732); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13C (22.96341463); KRAS_G12C, KRAS_G12V, TP53_V157F, KRAS_G13C (22.95731707);

[0583] EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G12A (22.94512195); KRAS_G12C, KRAS_G12D, KRAS_G12A, KRAS_G13D (22.94512195); EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_V157F (22.93902439); KRAS_G12C, EGFR_E746_A750del, TP53_R273L, KRAS_G13C (22.93902439); KRAS_G12C, KRAS_G12D, EGFR_T790M, EGFR_L861 Q (22.93292683); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A, EGFR_T790M (22.92682927); KRAS_G12C, KRAS_G12V, KRAS_G13D, EGFR_L861 Q (22.92682927);

[0584] KRAS_G12C, EGFR_E746_A750del, KRAS_G13C, EGFR_L861 Q (22.90853659); KRAS_G12C,

[0585] KRAS_G12V, TP53_R273L, KRAS_G13D (22.90853659); KRAS_G12C, KRAS_G12D,

[0586] EGFR_T790M, TP53_R158L (22.8902439); KRAS_G12C, KRAS_G12V, KRAS_G13C, TP53_R175H (22.88414634); KRAS_G12C, KRAS_G12V, KRAS_G13C, TP53_R273C (22.88414634); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R175H, TP53_R273C (22.87804878); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_V157F (22.87195122); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R273L (22.8597561); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C (22.84756098); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_L861 Q

[0587] (22.84756098); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, KRAS_G13C (22.82317073); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, KRAS_G13C (22.82317073); KRAS_G12C,

[0588] KRAS_G12V, TP53_R273L, EGFR_L861 Q (22.82317073); KRAS_G12C, KRAS_G12V, TP53_R158L,

[0589] KRAS_G13D (22.79878049); EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_T790M,

[0590] TP53_R273C (22.79268293); KRAS_G12C, KRAS_G12V, TP53_V157F, KRAS_G13D (22.79268293);

[0591] KRAS_G12C, EGFR_E746_A750del, TP53_R273L, KRAS_G13D (22.78658537); KRAS_G12C,

[0592] KRAS_G12D, KRAS_G12A, TP53_V157F (22.76219512); EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R175H (22.75609756); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R158L

[0593] (22.75609756); KRAS_G12C, EGFR_E746_A750del, KRAS_G13D, EGFR_L861 Q (22.75); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R175H (22.73780488); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R273C (22.73170732); KRAS_G12C, KRAS_G12V, KRAS_G13D, TP53_R175H (22.7195122); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273L

[0594] (22.7195122); KRAS_G12C, KRAS_G12V, KRAS_G13D, TP53_R273C (22.71341463); KRAS_G12C, KRAS_G12V, TP53_R158L, EGFR_L861 Q (22.71341463); KRAS_G12C, KRAS_G12V, TP53_V157F,

[0595] TP53_R273L (22.71341463); KRAS_G12C, KRAS_G12V, TP53_V157F, EGFR_L861 Q

[0596] (22.70121951); KRAS_G12C, EGFR_E746_A750del, KRAS_G13C, TP53_R175H (22.68902439); KRAS_G12C, EGFR_E746_A750del, TP53_R273L, EGFR_L861 Q (22.67682927); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, KRAS G13D (22.67073171); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, KRAS_G13D (22.67073171); KRAS_G12C, EGFR_E746_A750del, KRAS_G13C, TP53 R273C (22.66463415); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13D (22.65243902); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R175H (22.63414634); EGFR_L858R, EGFR_E746_A750del, , KRAS_G12V, TP53_R273L (22.62804878); KRAS_G12C, KRAS_G12V, TP53_R175H, EGFR_L861 Q

[0597] (22.62804878); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_R273L ( i22.62195122); KRAS_G12C, EGFR_E746_A750del, TP53_V157F, TP53_R273L (22.62195122); KRAS_G12C,

[0598] KRAS_G12D, KRAS_G12A, TP53_R273C (22.62195122); KRAS_G12C, KRAS_G12V, TP53_R273L,

[0599] TP53_R175H (22.62195122); KRAS_G12C, KRAS_G12V, TP53_R273L, TP53_R273C (22.61585366); KRAS_G12C, KRAS_G12V, TP53_R273C, EGFR_L861 Q (22.6097561);

[0600] KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_V157F (22.60365854); EGFR_L858R,

[0601] EGFR_E746_A750del, KRAS_G12V, TP53_R158L (22.59146341); EGFR_L858R

[0602] EGFR_E746_A750del, KRAS_G12V, EGFR_L861 Q (22.56097561); KRAS_G12C

[0603] EGFR_E746_A750del, TP53_R158L, EGFR_L861 Q (22.56097561); KRAS_G12C

[0604] EGFR_E746_A750del, TP53_V157F, EGFR_L861 Q (22.55487805); EGFR_L858R

[0605] EGFR_E746_A750del, KRAS_G12D, KRAS_G12A (22.54878049); KRAS_G12C EGFR_E746_A750del, KRAS_G13D, TP53_R175H (22.53658537); KRAS_G12C, EGFR_L858R (22.53658537); KRAS_G12C, EGFR_E746_A750del, EGFR_T790M (22.52439024); KRAS_G12C,

[0606] KRAS_G12V, TP53_R158L, TP53_R175H (22.51219512); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273C (22.51219512); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R175H

[0607] (22.51219512); KRAS_G12C, EGFR_E746_A750del, KRAS_G13D, TP53_R273C (22.50609756); KRAS_G12C, EGFR_E746_A750del, TP53_R158L, TP53_V157F (22.50609756); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R273C (22.50609756); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M (22.47560976); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_V157F (22.4695122); KRAS_G12C, EGFR_E746_A750del, TP53_R273L, TP53_R175H (22.4695122); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A, KRAS_G13C (22.44512195); EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G13C, KRAS_G13D (22.44512195); KRAS_G12C, EGFR_E746_A750del, TP53_R273L, TP53_R273C (22.43902439); KRAS_G12C, EGFR_E746_A750del, TP53_R175H, EGFR_L861Q (22.42073171); KRAS_G12C, KRAS_G12D, TP53_R273L, KRAS_G13C, KRAS_G13D (22.42073171); EGFR_L858R, KRAS_G12V,

[0608] KRAS_G12D, TP53_R273L, KRAS_G13C (22.41463415); KRAS_G12C, KRAS_G12V, TP53_R175H, TP53_R273C (22.41463415); KRAS_G12C, KRAS_G12D, KRAS_G13C, KRAS_G13D, EGFR_L861Q

[0609] (22.39634146); KRAS_G12C, EGFR_E746_A750del, TP53_R273C, EGFR_L861Q (22.37804878);

[0610] EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G13C, EGFR_L861Q (22.36585366);

[0611] EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R158L, KRAS_G13C (22.3597561); KRAS_G12C,

[0612] EGFR_E746_A750del, TP53_V157F, TP53_R175H (22.3597561); KRAS_G12C,

[0613] EGFR_E746_A750del, TP53_R158L, TP53_R175H (22.35365854); KRAS_G12C,

[0614] EGFR_E746_A750del, TP53_R158L, TP53_R273C (22.32926829); KRAS_G12C,

[0615] EGFR_E746_A750del, TP53_V157F, TP53_R273C (22.32926829); KRAS_G12C, KRAS_G12D,

[0616] TP53_R273L, KRAS_G13C, EGFR_L861Q (22.32317073); KRAS_G12C, KRAS_G12D,

[0617] TP53_R158L, KRAS_G13C, KRAS_G13D (22.29268293); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R273C (22.28658537); KRAS_G12C, KRAS_G12D, TP53_V157F, KRAS_G13C,

[0618] KRAS_G13D (22.28658537); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R175H

[0619] (22.26219512); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_R273L, KRAS_G13C

[0620] (22.24390244); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A, KRAS_G13D

[0621] (22.23780488); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R273L, KRAS_G13D

[0622] (22.23780488); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_V157F, KRAS_G13C

[0623] (22.23780488); KRAS_G12C, KRAS_G12D, TP53_V157F, TP53_R273L, KRAS_G13C

[0624] (22.23780488); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R273L

[0625] (22.23170732); KRAS_G12C, KRAS_G12V, KRAS_G13C (22.22560976); EGFR_L858R,

[0626] KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_R273L (22.19512195); KRAS_G12C, KRAS_G12D, KRAS_G13C, KRAS_G13D, TP53_R175H (22.19512195); KRAS_G12C, KRAS_G12D, TP53_R158L,

[0627] KRAS_G13C, EGFR_L861Q (22.19512195); EGFR_L858R, KRAS_G12V, KRAS_G12D,

[0628] TP53_R158L, KRAS_G13D (22.18902439); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A, EGFR_L861Q (22.18292683); EGFR_L858R, KRAS_G12V, KRAS_G12D,

[0629] KRAS_G13D, EGFR_L861Q (22.18292683); KRAS_G12C, KRAS_G12D, KRAS_G13C,

[0630] KRAS_G13D, TP53_R273C (22.18292683); KRAS_G12C, KRAS_G12D, TP53_V157F, KRAS_G13C,

[0631] EGFR_L861Q (22.18292683); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A,

[0632] TP53_R158L (22.17682927); KRAS_G12C, EGFR_E746_A750del, TP53_R175H, TP53_R273C

[0633] (22.17682927); KRAS_G12C, KRAS_G12D, TP53_R273L, KRAS_G13D, EGFR_L861Q

[0634] (22.17682927); EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_T790M (22.16463415);

[0635] EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R273L, EGFR_L861 Q (22.16463415);

[0636] KRAS_G12C, KRAS_G12D, TP53_R273L, KRAS_G13C, TP53_R175H (22.12804878);

[0637] EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G13C, TP53_R273C (22.12195122);

[0638] KRAS_G12C, KRAS_G12D, TP53_R273L, KRAS_G13C, TP53_R273C (22.11585366);

[0639] EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R158L, EGFR_L861Q (22.1097561); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_V157F, KRAS_G13C (22.1097561); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_R273L, KRAS_G13D (22.10365854); KRAS_G12C, KRAS_G12D, TP53_V157F,

[0640] TP53_R273L, KRAS_G13D (22.09756098); KRAS_G12C, KRAS_G12D, EGFR_T790M (22.09146341); KRAS_G12C, KRAS_G12D, KRAS_G13C, TP53_R175H, EGFR_L861Q (22.09146341); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_V157F (22.07926829); EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G13C, TP53_R175H

[0641] (22.07926829); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C, KRAS_G13D (22.06707317); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_V157F, TP53_R273L

[0642] (22.06707317); KRAS_G12C, KRAS_G12D, KRAS_G13C, TP53_R273C, EGFR_L861Q (22.06707317); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R273L, KRAS_G13C (22.06097561); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_V157F, KRAS_G13D (22.06097561); KRAS_G12C, KRAS_G12V, KRAS_G13D (22.05487805); KRAS_G12C, KRAS_G12D, TP53_R158L, KRAS_G13D, EGFR_L861Q (22.04878049); KRAS_G12C, EGFR_E746_A750del, KRAS_G13C (22.03658537); KRAS_G12C, KRAS_G12D, TP53_V157F, KRAS_G13D, EGFR_L861Q (22.03658537); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R158L, KRAS_G13C (22.01829268); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R158L,

[0643] TP53_V157F (22.01829268); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_R273L, EGFR_L861Q (22.01219512); KRAS_G12C, KRAS_G12D, TP53_R158L, KRAS_G13C, TP53_R175H (22); KRAS_G12C, KRAS_G12D, TP53_V157F, KRAS_G13C, TP53_R175H (22); KRAS_G12C, KRAS_G12D, TP53_V157F, TP53_R273L, EGFR_L861Q (22); KRAS_G12C, KRAS_G12D, TP53_R158L, KRAS_G13C, TP53_R273C (21.99390244); KRAS_G12C, KRAS_G12D, TP53_R273L, KRAS_G13D, TP53_R175H (21.98780488); KRAS_G12C, KRAS_G12D, TP53_V157F, KRAS_G13C, TP53_R273C (21.98780488); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_V157F, EGFR_L861Q (21.98170732); KRAS_G12C, KRAS_G12D, KRAS_G12A (21.98170732); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_V157F, KRAS_G13D (21.9695122); KRAS_G12C, KRAS_G12D, TP53_R273L, KRAS_G13D, TP53_R273C (21.9695122); KRAS_G12C, KRAS_G12V, EGFR_L861Q (21.96341463); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C, EGFR_L861Q (21.95731707); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_V157F, TP53_R273L (21.95731707); KRAS_G12C, KRAS_G12V, TP53_R273L (21.95731707); KRAS_G12C, KRAS_G12D, KRAS_G13D, TP53_R175H, EGFR_L861Q (21.94512195); EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G13D, TP53_R273C (21.93902439); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R273L, TP53_R273C (21 .92682927); KRAS_G12C, KRAS_G12D, KRAS_G13D, TP53_R273C, EGFR_L861Q (21.91463415); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R273C (21.90853659); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R273L, KRAS_G13D (21.90243902); EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G13D, TP53_R175H (21.90243902); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R158L, TP53_R273L (21 .89634146); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R273L, TP53_R175H (21.8902439); KRAS_G12C, KRAS_G12D, TP53_R273L, TP53_R175H, EGFR_L861Q (21.8902439); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, KRAS_G13C (21.88414634); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_R273C (21.88414634);

[0644] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R175H (21.87804878); KRAS_G12C, EGFR_E746_A750del, KRAS_G13D (21.87804878); KRAS_G12C, KRAS_G12D, KRAS_G13C, TP53_R175H, TP53_R273C (21.87804878); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, KRAS_G13C (21.87195122); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_V157F, EGFR_L861Q (21.87195122); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R158L, KRAS_G13D (21.86585366); KRAS_G12C, KRAS_G12D, TP53_R158L, KRAS_G13D, TP53_R175H (21.8597561); KRAS_G12C, KRAS_G12D, TP53_R273L, TP53_R273C, EGFR_L861Q (21.8597561); KRAS_G12C, KRAS_G12D, TP53_V157F, KRAS_G13D, TP53_R175H (21.8597561); KRAS_G12C, KRAS_G12V, TP53_R158L (21 .85365854); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R273C, EGFR_L861Q (21.84756098); KRAS_G12C, KRAS_G12D, TP53_R158L, KRAS_G13D, TP53_R273C (21.84756098); KRAS_G12C, KRAS_G12V, TP53_V157F

[0645] (21.84756098); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_R175H

[0646] (21.84146341); KRAS_G12C, KRAS_G12D, TP53_V157F, KRAS_G13D, TP53_R273C

[0647] (21.84146341); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_R273L, TP53_R175H

[0648] (21.82926829); KRAS_G12C, KRAS_G12D, TP53_V157F, TP53_R273L, TP53_R175H

[0649] (21.82926829); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R175H, EGFR_L861Q

[0650] (21.82317073); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_R273L, TP53_R273C

[0651] (21.81707317); KRAS_G12C, EGFR_E746_A750del, TP53_R273L (21.81097561); KRAS_G12C,

[0652] KRAS_G12D, TP53_V157F, TP53_R273L, TP53_R273C (21.81097561); EGFR_L858R,

[0653] EGFR_E746_A750del, KRAS_G12D, TP53_R273L, EGFR_L861Q (21.79878049); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D, EGFR_L861Q (21.79268293); KRAS_G12C, EGFR_E746_A750del, EGFR_L861Q (21.76219512); KRAS_G12C, KRAS_G12A, EGFR_T790M,

[0654] KRAS_G13C, KRAS_G13D (21 .76219512); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_R175H, EGFR_L861Q (21.76219512); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R158L, EGFR_L861Q (21.75609756); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, TP53_R273L (21.75609756); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_V157F, TP53_R273C (21.75609756); KRAS_G12C, KRAS_G12D, TP53_V157F, TP53_R175H, EGFR_L861Q

[0655] (21.75609756); KRAS_G12C, KRAS_G12V, TP53_R175H (21.75609756); KRAS_G12C,

[0656] KRAS_G12V, TP53_R273C (21.75); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_R273C, EGFR_L861Q (21.73780488); KRAS_G12C, KRAS_G12D, KRAS_G13D, TP53_R175H,

[0657] TP53_R273C (21.73170732); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, KRAS_G13D (21.72560976); KRAS_G12C, KRAS_G12D, TP53_V157F, TP53_R273C, EGFR_L861Q (21.72560976); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R158L, TP53_V157F (21.7195122); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_V157F, TP53_R175H (21.7195122); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, KRAS_G13D (21.70731707); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_R273L (21.70731707); KRAS_G12C, EGFR_E746_A750del, TP53_R158L (21.70121951); KRAS_G12C,

[0658] EGFR_E746_A750del, TP53_V157F (21.70121951); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_V157F, TP53_R175H (21.70121951); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_R158L (21.68902439); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_V157F, TP53_R273C (21.68902439); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C, TP53_R273C (21 .68292683); KRAS_G12C, KRAS_G12D, TP53_R273L, TP53_R175H, TP53_R273C (21.68292683); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C, TP53_R175H (21.67073171); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V (21.67073171); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R273L, KRAS_G13C (21.64634146);

[0659] KRAS_G12C, KRAS_G12A, EGFR_T790M, KRAS_G13C, EGFR_L861Q (21.62195122);

[0660] EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, EGFR_L861Q (21.61585366); KRAS_G12C, KRAS_G12D, TP53_R175H, TP53_R273C, EGFR_L861Q (21.61585366);

[0661] EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R175H, TP53_R273C (21.57926829);

[0662] EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, EGFR_L861Q (21.56707317); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_R175H, TP53_R273C (21.56097561); KRAS_G12C, KRAS_G12D, TP53_V157F, TP53_R175H, TP53_R273C (21.56097561); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_V157F, KRAS_G13C (21.55487805); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_V157F (21.54878049); KRAS_G12C, EGFR_E746_A750del, TP53_R175H (21.54878049); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R158L,

[0663] KRAS_G13C (21.54878049); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R273L, TP53_R273C (21.5304878); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R273L, TP53_R175H (21.52439024); KRAS_G12C, KRAS_G12D, KRAS_G13C, KRAS_G13D

[0664] (21.52439024); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D, TP53_R273C (21.51829268); KRAS_G12C, EGFR_E746_A750del, TP53_R273C (21.51829268); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D, TP53_R175H (21.51219512); EGFR_L858R,

[0665] EGFR_E746_A750del, KRAS_G12D, TP53_R158L, TP53_R273C (21 .5); EGFR_L858R,

[0666] EGFR_E746_A750del, KRAS_G12D, TP53_R158L, TP53_R175H (21.48780488); KRAS_G12C,

[0667] KRAS_G12A, EGFR_T790M, TP53_R273L, KRAS_G13D (21.48170732); EGFR_L858R,

[0668] KRAS_G12V, KRAS_G12D, KRAS_G13C (21.47560976); EGFR_E746_A750del, KRAS_G12V,

[0669] KRAS_G12D, EGFR_T790M, KRAS_G13C (21.45731707); KRAS_G12C, KRAS_G12D, TP53_R273L, KRAS_G13C (21.45731707); KRAS_G12C, KRAS_G12A, EGFR_T790M, KRAS_G13C, TP53_R175H (21.45121951); KRAS_G12C, KRAS_G12A, EGFR_T790M, KRAS_G13D, EGFR_L861 Q (21.45121951); KRAS_G12C, KRAS_G12A, EGFR_T790M,

[0670] KRAS_G13C, TP53_R273C (21 .44512195); KRAS_G12C, KRAS_G12D, KRAS_G13C, EGFR_L861 Q (21.42073171); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R175H, EGFR_L861 Q (21.40243902); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R273C, EGFR_L861 Q (21.39634146); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_V157F, KRAS_G13D

[0671] (21.3902439); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R158L, KRAS_G13D

[0672] (21.38414634); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, TP53_R273C (21.3597561); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, TP53_R175H (21.35365854); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R273L, EGFR_L861 Q

[0673] (21.34756098); KRAS_G12C, KRAS_G12D, TP53_R158L, KRAS_G13C (21.33536585);

[0674] KRAS_G12C, KRAS_G12D, TP53_V157F, KRAS_G13C (21.32926829); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_R273C (21.31707317); EGFR_L858R,

[0675] EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_R175H (21.31097561); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_V157F, TP53_R273L (21 .31097561); KRAS_G12C, KRAS_G12D, TP53_R273L, KRAS_G13D (21.31097561); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273L (21.30487805); EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G13D (21.29268293); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A (21.28658537); KRAS_G12C, KRAS_G12A, EGFR_T790M, KRAS_G13D, TP53_R175H (21.28658537);

[0676] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R273L (21.2804878); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R273L (21 .2804878); KRAS_G12C, KRAS_G12A, EGFR_T790M, KRAS_G13D, TP53_R273C (21.27439024); KRAS_G12C, KRAS_G12D,

[0677] KRAS_G13D, EGFR_L861 Q (21.26829268); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_T790M, KRAS_G13D (21 .26219512); KRAS_G12C, KRAS_G12A, EGFR_T790M,

[0678] TP53_R158L, EGFR_L861 Q (21.25); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_V157F, EGFR_L861 Q (21.25); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R158L (21.23780488); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R158L (21.22560976); KRAS_G12C, KRAS_G12D, KRAS_G13C, TP53_R175H (21.2195122); EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_L861 Q (21.21341463); KRAS_G12C, KRAS_G12A, EGFR_T790M,

[0679] TP53_R158L, TP53_V157F (21.21341463); KRAS_G12C, KRAS_G12D, TP53_R273L, EGFR_L861 Q (21.21341463); KRAS_G12C, KRAS_G12D, KRAS_G13C, TP53_R273C (21.20731707);

[0680] KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R273L, TP53_R175H (21 .18902439);

[0681] KRAS_G12C, KRAS_G12D, TP53_R158L, KRAS_G13D (21.18902439); KRAS_G12C, KRAS_G12D, TP53_V157F, KRAS_G13D (21.18292683); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_T790M, EGFR_L861 Q (21.17682927); KRAS_G12C, KRAS_G12A, EGFR_T790M,

[0682] TP53_R273L, TP53_R273C (21.17682927); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_R273L (21.15853659); KRAS_G12C, KRAS_G12D, TP53_V157F, TP53_R273L (21.15243902);

[0683] KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R175H, EGFR_L861 Q (21.14634146);

[0684] EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R175H, TP53_R273C (21.12804878); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R273C, EGFR_L861 Q (21.12195122);

[0685] EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_V157F (21.1097561); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_V157F (21 .10365854); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_V157F, TP53_R175H (21.10365854); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R175H (21.09756098); KRAS_G12C, KRAS_G12A,

[0686] EGFR_T790M, TP53_V157F, TP53_R273C (21.09146341); KRAS_G12C, KRAS_G12D,

[0687] TP53_R158L, EGFR_L861 Q (21.09146341); KRAS_G12C, KRAS_G12V (21.09146341);

[0688] KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R158L, TP53_R273C (21 .08536585);

[0689] KRAS_G12C, KRAS_G12D, TP53_V157F, EGFR_L861 Q (21 .07926829); KRAS_G12C, KRAS_G12D, KRAS_G13D, TP53_R175H (21.07317073); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C (21.06707317); KRAS_G12C, KRAS_G12D, KRAS_G13D, TP53_R273C (21.05487805); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_V157F (21.0304878); KRAS_G12C, KRAS_G12D, TP53_R273L, TP53_R175H (21.02439024); KRAS_G12C, KRAS_G12D, TP53_R273L, TP53_R273C (21 .00609756); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R273C (20.9695122); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R175H, TP53_R273C (20.9695122); KRAS_G12C, KRAS_G12D, TP53_R175H, EGFR_L861 Q (20.9695122); KRAS_G12C, KRAS_G12D, TP53_R273C, EGFR_L861 Q (20.93902439); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R273C (20.93292683); EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R175H

[0690] (20.93292683); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R273L (20.91463415); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D (20.90243902); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_R175H (20.90243902); KRAS_G12C, KRAS_G12D, TP53_V157F, TP53_R175H (20.90243902); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R175H (20.89634146); KRAS_G12C, EGFR_E746_A750del (20.8902439); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_R273C (20.8902439); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R158L (20.88414634); KRAS_G12C, KRAS_G12D, TP53_V157F, TP53_R273C (20.88414634); EGFR_L858R, KRAS_G12V, KRAS_G12A, EGFR_T790M, KRAS_G13C (20.85365854); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_L861 Q (20.79268293); KRAS_G12C, KRAS_G12A, EGFR_T790M, KRAS_G13C (20.78658537); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R273L, KRAS_G13C (20.7804878); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13C, KRAS_G13D (20.76829268); KRAS_G12C, KRAS_G12D, TP53_R175H, TP53_R273C (20.75609756); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_V157F (20.74390244); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13C, EGFR_L861 Q (20.71341463); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R158L, KRAS_G13C (20.70731707); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M (20.70731707); EGFR_L858R, KRAS_G12V, KRAS_G12A, EGFR_T790M, KRAS_G13D (20.64634146); KRAS_G12C, KRAS_G12A, EGFR_T790M, KRAS_G13D (20.61585366); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R273L, KRAS_G13D (20.59146341); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_V157F, KRAS_G13C (20.59146341); EGFR_L858R, KRAS_G12V, KRAS_G12A, EGFR_T790M, TP53_R273L (20.58536585);

[0691] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_R273L (20.57317073); EGFR_L858R, KRAS_G12V, KRAS_G12A, EGFR_T790M, TP53_R158L (20.57317073);

[0692] KRAS_G12C, KRAS_G12D, KRAS_G13C (20.54878049); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R273L, EGFR_L861 Q (20.54268293); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R158L, KRAS_G13D (20.52439024); EGFR_L858R, KRAS_G12V, KRAS_G12A, EGFR_T790M, EGFR_L861 Q (20.52439024); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13D, EGFR_L861 Q (20.51829268); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R273C (20.51829268); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R273L

[0693] (20.51829268); EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R175H (20.51219512); KRAS_G12C, KRAS_G12A, EGFR_T790M, EGFR_L861 Q (20.47560976); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R158L, EGFR_L861 Q (20.4695122); EGFR_L858R, KRAS_G12V, KRAS_G12A, EGFR_T790M, TP53_V157F (20.4695122); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_V157F, TP53_R273L (20.45731707); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13C, TP53_R273C (20.44512195); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_V157F (20.43292683); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R158L (20.42682927); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13C, TP53_R175H (20.41463415); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_V157F,

[0694] KRAS_G13D (20.40853659); KRAS_G12C, KRAS_G12D, KRAS_G13D (20.39634146); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_V157F (20.3902439); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_V157F, EGFR_L861 Q (20.35365854); KRAS_G12C, KRAS_G12D, TP53_R273L (20.34756098); EGFR_L858R, KRAS_G12V, KRAS_G12A,

[0695] EGFR_T790M, TP53_R273C (20.32317073); EGFR_L858R, KRAS_G12V, KRAS_G12D

[0696] (20.32317073); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R175H (20.31097561); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_T790M (20.29878049); KRAS_G12C, KRAS_G12A, EGFR_T790M, TP53_R273C (20.29878049); EGFR_L858R, KRAS_G12V, KRAS_G12A, EGFR_T790M, TP53_R175H (20.29268293); KRAS_G12C, KRAS_G12D, EGFR_L861 Q (20.29268293); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R273L, TP53_R273C (20.2804878); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R273L, TP53_R175H (20.25609756); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13D, TP53_R273C (20.25); KRAS_G12C, KRAS_G12D, TP53 R158L (20.23170732);

[0697] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13D, TP53_R175H (20.22560976); KRAS_G12C, KRAS_G12D, TP53_V157F (20.22560976); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_R273C (20.2195122); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_R175H (20.18902439); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R273C, EGFR_L861 Q (20.18292683); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R175H, EGFR L861 Q (20.17073171); EGFR_E746_A750del, KRAS_G12V,

[0698] KRAS_G12D, TP53_V157F, TP53_R273C (20.10365854); KRAS_G12C, KRAS_G12D, TP53_R175H (20.09756098); EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_V157F, TP53_R175H (20.07926829); KRAS_G12C, EGFR_T790M, TP53_R273L, KRAS_G13C, KRAS_G13D (20.07926829); KRAS_G12C, KRAS_G12D, TP53_R273C (20.07926829); KRAS_G12C, EGFR_T790M, KRAS_G13C, KRAS_G13D, EGFR_L861 Q (20.02439024). Similarly, when an expected coverage of at least 30% of all lung cancer patients is desired, then any of the following combinations can be used (with coverage % calculated in the MSKCC BPC Smoker & LUAD cohorts provided in brackets), and are explicitly envisaged herein, as are any combinations including these mutations and additional mutations: KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D (47.25609756); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G12A (46.95121951); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G13C (45.12195122); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R158L (44.81707317); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A (44.51219512); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_V157F (44.51219512); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G13D (44.20731707); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_T790M (43.90243902); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53 R273L (43.59756098); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A (43.29268293); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D (43.29268293); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, EGFR_L861 Q (43.29268293); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53_R175H (43.29268293); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12D, TP53 R273C (43.29268293); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C (42.68292683);

[0699] KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12A, KRAS_G13C (42.37804878); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R158L (42.07317073); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A (41.76829268); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G13D (41.76829268); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_V157F (41.76829268); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12A, TP53_R158L (41.76829268); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12A, TP53_V157F (41.76829268); KRAS_G12C,

[0700] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13C (41.46341463); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R175H (41.46341463); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, TP53_R273L (41.46341463); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12A, KRAS_G13D (41.46341463); KRAS_G12C,

[0701] EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R158L (41.15853659); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12A, EGFR_T790M (41 .15853659); KRAS_G12C,

[0702] EGFR_L858R, KRAS_G12V, KRAS_G12A, TP53_R175H (41.15853659); KRAS_G12C,

[0703] EGFR_L858R, KRAS_G12V, KRAS_G12A, TP53_R273L (41 .15853659); KRAS_G12C, KRAS_G12V,

[0704] KRAS_G12D, KRAS_G12A, KRAS_G13C (41.15853659); KRAS_G12C, EGFR_L858R,

[0705] EGFR_E746_A750del, KRAS_G12V (40.85365854); KRAS_G12C, EGFR_L858R,

[0706] EGFR_E746_A750del, KRAS_G12V, EGFR_L861 Q (40.85365854); KRAS_G12C, EGFR_L858R,

[0707] EGFR_E746_A750del, KRAS_G12V, EGFR_T790M (40.85365854); KRAS_G12C, EGFR_L858R,

[0708] EGFR_E746_A750del, KRAS_G12V, TP53_R273C (40.85365854); KRAS_G12C, KRAS_G12V,

[0709] KRAS_G12D, KRAS_G12A, EGFR_T790M (40.85365854); KRAS_G12C, KRAS_G12V, KRAS_G12D,

[0710] KRAS_G12A, TP53_R158L (40.85365854); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V,

[0711] KRAS_G12D, EGFR_T790M (40.54878049); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V,

[0712] KRAS_G12D, KRAS_G13D (40.54878049); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V,

[0713] KRAS_G12D, TP53_V157F (40.54878049); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12A

[0714] (40.54878049); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12A, EGFR_L861 Q

[0715] (40.54878049); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G12A, TP53_R273C

[0716] (40.54878049); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_V157F

[0717] (40.54878049); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R158L, KRAS_G13C

[0718] (40.24390244); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, KRAS_G13D

[0719] (40.24390244); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R175H

[0720] (39.93902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53_R273L

[0721] (39.93902439); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C

[0722] (39.93902439); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_V157F, KRAS_G13C (39.93902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D (39.63414634); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, EGFR_L861 Q (39.63414634); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, TP53 R273C (39.63414634);

[0723] KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, KRAS_G13C (39.63414634); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13C, KRAS_G13D (39.63414634); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R158L, TP53_V157F (39.63414634); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R175H (39.63414634); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R273L (39.63414634); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R158L (39.32926829); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, KRAS_G13C (39.32926829); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13C, TP53_R175H (39.32926829); KRAS_G12C, EGFR_L858R, KRAS_G12V,

[0724] TP53_R158L, KRAS_G13D (39.32926829); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273L, KRAS_G13C (39.32926829); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A (39.32926829); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, EGFR_L861 Q (39.32926829); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G12A, TP53_R273C (39.32926829); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L, KRAS_G13C (39.32926829); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D (39.02439024); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_V157F (39.02439024); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, TP53_R158L (39.02439024); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, TP53_V157F (39.02439024); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, TP53_R158L (39.02439024); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R158L, TP53 R175H (39.02439024); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R158L, TP53_R273L (39.02439024); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_V157F, KRAS_G13D (39.02439024); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, KRAS_G13C (39.02439024); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, KRAS_G13C (38.7195122); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, KRAS_G13D (38.7195122); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13C (38.7195122); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13C, EGFR_L861 Q (38.7195122); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13C, TP53_R273C (38.7195122); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_V157F, TP53_R175H (38.7195122); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_V157F, TP53_R273L (38.7195122); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R158L (38.7195122); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_V157F (38.7195122); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_V157F, KRAS_G13C (38.7195122); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R273L (38.41463415); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, EGFR_T790M (38.41463415); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, KRAS_G13D (38.41463415); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, TP53 V157F (38.41463415); KRAS_G12C, EGFR_L858R,

[0725] KRAS_G12V, KRAS_G13D, TP53_R175H (38.41463415); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R158L (38.41463415); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R158L,

[0726] EGFR_L861 Q (38.41463415); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R158L,

[0727] TP53_R273C (38.41463415); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273L , KRAS_G13D (38.41463415); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13C, KRAS_G13D (38.41463415); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L, KRAS_G13D (38.41463415); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V , KRAS_G12A, TP53_R158L (38.1097561); KRAS_G12C, EGFR_L858R, EGFR_E746 A750del, KRAS_G12D (38.1097561); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_L861 Q (38.1097561); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M (38.1097561); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53_R175H (38.1097561); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12D, TP53 R273C (38.1097561); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, TP53_R273L (38.1097561); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, TP53_R175H (38.1097561); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, TP53 R273L (38.1097561); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273L, TP53_R175H (38.1097561); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_V157F (38.1097561); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_V157F, EGFR_L861 Q (38.1097561); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_V157F, TP53_R273C (38.1097561); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, KRAS_G13D (38.1097561); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_V157F (38.1097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, EGFR_T790M (37.80487805); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, KRAS_G13D (37.80487805); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, TP53_R175H (37.80487805); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, TP53_V157F (37.80487805); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A (37.80487805); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, EGFR_L861 Q (37.80487805); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, TP53 R175H (37.80487805); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G12A, TP53_R273C (37.80487805); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13D (37.80487805); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13D, EGFR_L861 Q (37.80487805); KRAS_G12C, EGFR_L858R, KRAS_G12V, KRAS_G13D,

[0728] TP53_R273C (37.80487805); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13C, TP53_R175H (37.80487805); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_R175H (37.80487805); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_R273L (37.80487805); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R273L, KRAS G13C

[0729] (37.80487805); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_V157F, KRAS_G13D (37.80487805); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, TP53_R273L (37.5); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, KRAS_G13C (37.5); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M (37.5); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, EGFR_L861 Q (37.5); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_T790M, TP53_R273C (37.5); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R175H (37.5); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R175H, EGFR_L861 Q (37.5); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R175H, TP53_R273C (37.5); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273L (37.5); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273L, EGFR_L861 Q (37.5); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273L, TP53_R273C (37.5); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53_R175H (37.5); KRAS_G12C, KRAS_G12V, KRAS_G12D,

[0730] EGFR_T790M, TP53_R273L (37.5); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13C (37.5); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13C, EGFR_L861 Q (37.5); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13C, TP53_R273C (37.5); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L (37.5); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L,

[0731] EGFR_L861 Q (37.5); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R158L, TP53_R273C (37.5); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, KRAS_G13C (37.19512195); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_V157F, KRAS_G13C (37.19512195); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M (37.19512195); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, EGFR_L861 Q (37.19512195); KRAS_G12C, KRAS_G12V, KRAS_G12D, EGFR_T790M, TP53 R273C (37.19512195); KRAS_G12C, KRAS_G12V, KRAS_G12D,

[0732] TP53_V157F, TP53_R175H (37.19512195); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_V157F, TP53_R273L (37.19512195); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A (36.8902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, EGFR_L861 Q (36.8902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G12A, TP53 R273C

[0733] (36.8902439); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13C, KRAS_G13D (36.8902439); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, TP53_V157F (36.8902439); KRAS_G12C, EGFR_L858R, KRAS_G12V (36.8902439); KRAS_G12C, EGFR_L858R, KRAS_G12V, EGFR_L861 Q (36.8902439); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273C (36.8902439); KRAS_G12C, EGFR_L858R, KRAS_G12V, TP53_R273C, EGFR_L861 Q (36.8902439); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13D, TP53_R175H (36.8902439); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R273L, KRAS_G13D (36.8902439); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_V157F (36.8902439); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_V157F, EGFR_L861 Q (36.8902439); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_V157F, TP53_R273C (36.8902439); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, KRAS_G13C (36.58536585); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, KRAS_G13C (36.58536585); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, KRAS_G13D (36.58536585); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13D (36.58536585); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13D,

[0734] EGFR_L861 Q (36.58536585); KRAS_G12C, KRAS_G12V, KRAS_G12D, KRAS_G13D, TP53_R273C (36.58536585); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, KRAS_G13D (36.2804878); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, TP53_R158L (36.2804878); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, TP53_V157F (36.2804878); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, TP53 R158L

[0735] (36.2804878); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273L, KRAS_G13C (36.2804878); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_V157F, KRAS_G13D (36.2804878); KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_T790M, KRAS_G13C (36.2804878); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L, KRAS_G13C (36.2804878); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R273L, TP53_R175H (36.2804878); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, KRAS_G13C (35.97560976); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, KRAS_G13C (35.97560976); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C, KRAS G13D (35.97560976); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C, TP53_R175H (35.97560976); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, KRAS_G13C (35.97560976); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, TP53_R175H (35.97560976); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, TP53_R273L (35.97560976); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13C

[0736] (35.97560976); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13C, EGFR_L861 Q

[0737] (35.97560976); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13C, TP53_R175H

[0738] (35.97560976); KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13C, TP53_R273C

[0739] (35.97560976); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, TP53_R273L

[0740] (35.97560976); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_V157F, KRAS_G13C (35.97560976); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R175H (35.97560976); KRAS_G12C, KRAS_G12V,

[0741] KRAS_G12D, TP53_R175H, EGFR_L861 Q (35.97560976); KRAS_G12C, KRAS_G12V,

[0742] KRAS_G12D, TP53_R175H, TP53_R273C (35.97560976); KRAS_G12C, KRAS_G12V, KRAS_G12D,

[0743] TP53_R273L (35.97560976); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R273L, EGFR_L861 Q

[0744] (35.97560976); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R273L, TP53_R273C

[0745] (35.97560976); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, KRAS_G13D

[0746] (35.67073171); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, TP53_R175H

[0747] (35.67073171); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, TP53_V157F

[0748] (35.67073171); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273L, KRAS G13C

[0749] (35.67073171); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, KRAS_G13D

[0750] (35.67073171); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, TP53_V157F

[0751] (35.67073171); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L (35.67073171);

[0752] KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, EGFR_L861 Q (35.67073171);

[0753] KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, TP53_R175H (35.67073171);

[0754] KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R158L, TP53_R273C (35.67073171);

[0755] KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_V157F, TP53_R273L (35.67073171); KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_T790M, TP53_R158L (35.67073171); KRAS_G12C, KRAS_G12V,

[0756] KRAS_G12A, KRAS_G13C, KRAS_G13D (35.67073171); KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13C, TP53_R175H (35.67073171); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L,

[0757] TP53_V157F (35.67073171); KRAS_G12C, KRAS_G12V, KRAS_G12D (35.67073171); KRAS_G12C,

[0758] KRAS_G12V, KRAS_G12D, EGFR_L861 Q (35.67073171); KRAS_G12C, KRAS_G12V, KRAS_G12D,

[0759] TP53_R273C (35.67073171); KRAS_G12C, KRAS_G12V, KRAS_G12D, TP53_R273C, EGFR_L861 Q

[0760] (35.67073171); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_R158L

[0761] (35.36585366); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_R158L

[0762] (35.36585366); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, TP53_R273L

[0763] (35.36585366); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A (35.36585366);

[0764] KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, EGFR_L861 Q (35.36585366)

[0765] KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M (35.36585366)

[0766] KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G12A, TP53_R273C (35.36585366)

[0767] KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273L, KRAS_G13D (35.36585366);

[0768] KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_V157F (35.36585366); KRAS_G12C,

[0769] EGFR_L858R, KRAS_G12D, TP53_V157F, EGFR_L861 Q (35.36585366); KRAS_G12C,

[0770] EGFR_L858R, KRAS_G12D, TP53_V157F, TP53_R175H (35.36585366); KRAS_G12C,

[0771] EGFR_L858R, KRAS_G12D, TP53_V157F, TP53_R273C (35.36585366); KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_T790M, KRAS_G13D (35.36585366); KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_T790M, TP53_R175H (35.36585366); KRAS_G12C, KRAS_G12V, KRAS_G12A,

[0772] EGFR_T790M, TP53_V157F (35.36585366); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L, KRAS_G13D (35.36585366); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L, TP53_R175H

[0773] (35.36585366); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R273L, KRAS_G13C

[0774] (35.36585366); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, EGFR_T790M (35.06097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, KRAS_G13D (35.06097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_V157F (35.06097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, KRAS_G13D (35.06097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_R175H (35.06097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_V157F (35.06097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C (35.06097561);

[0775] KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C, EGFR_L861Q (35.06097561);

[0776] KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13C, TP53_R273C (35.06097561);

[0777] KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13D, TP53_R175H (35.06097561);

[0778] KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, KRAS_G13D (35.06097561);

[0779] KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, TP53_R175H (35.06097561);

[0780] KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, TP53_R273L (35.06097561);

[0781] KRAS_G12C, EGFR_L858R, KRAS_G12D, KRAS_G13D (35.06097561); KRAS_G12C,

[0782] EGFR_L858R, KRAS_G12D, KRAS_G13D, EGFR_L861Q (35.06097561); KRAS_G12C,

[0783] EGFR_L858R, KRAS_G12D, KRAS_G13D, TP53_R175H (35.06097561); KRAS_G12C,

[0784] EGFR_L858R, KRAS_G12D, KRAS_G13D, TP53_R273C (35.06097561); KRAS_G12C,

[0785] KRAS_G12V, KRAS_G12A, EGFR_T790M, TP53_R273L (35.06097561); KRAS_G12C, KRAS_G12V,

[0786] KRAS_G12A, TP53_R158L, TP53_R273L (35.06097561); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_V157F, KRAS_G13D (35.06097561); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_V157F,

[0787] TP53_R175H (35.06097561); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_R273L (34.75609756); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L

[0788] (34.75609756); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, EGFR_L861Q

[0789] (34.75609756); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R158L, TP53_R273C

[0790] (34.75609756); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273L, KRAS_G13D

[0791] (34.75609756); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273L, TP53_R175H

[0792] (34.75609756); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, TP53_R273L

[0793] (34.75609756); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R158L, KRAS_G13C

[0794] (34.75609756); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M (34.75609756);

[0795] KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, EGFR_L861Q (34.75609756);

[0796] KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, TP53_R175H (34.75609756);

[0797] KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_T790M, TP53_R273C (34.75609756);

[0798] KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13C (34.75609756); KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13C, EGFR_L861Q (34.75609756); KRAS_G12C, KRAS_G12V, KRAS_G12A,

[0799] KRAS_G13C, TP53_R273C (34.75609756); KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13D, TP53_R175H (34.75609756); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_V157F, TP53_R273L

[0800] (34.75609756); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_R175H

[0801] (34.45121951); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_R273L

[0802] (34.45121951); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13C, KRAS_G13D

[0803] (34.45121951); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_V157F, KRAS_G13C

[0804] (34.45121951); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R158L, KRAS_G13C

[0805] (34.45121951); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_V157F, KRAS_G13C

[0806] (34.45121951); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273L (34.45121951);

[0807] KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273L, EGFR_L861Q (34.45121951);

[0808] KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273L, TP53_R175H (34.45121951);

[0809] KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273L, TP53_R273C (34.45121951);

[0810] KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_T790M (34.45121951); KRAS_G12C, KRAS_G12V,

[0811] KRAS_G12A, EGFR_T790M, EGFR_L861Q (34.45121951); KRAS_G12C, KRAS_G12V,

[0812] KRAS_G12A, EGFR_T790M, TP53_R273C (34.45121951); KRAS_G12C, KRAS_G12V,

[0813] KRAS_G12A, TP53_R158L (34.45121951); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L, EGFR_L861Q (34.45121951); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R158L, TP53_R273C

[0814] (34.45121951); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R273L, KRAS_G13D (34.45121951); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R273L, TP53_R175H

[0815] (34.45121951); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A (34.14634146);

[0816] KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, EGFR_L861 Q (34.14634146);

[0817] KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G12A, TP53_R273C (34.14634146);

[0818] KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M (34.14634146); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, EGFR_L861 Q (34.14634146); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, EGFR_T790M, TP53_R273C (34.14634146); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, KRAS_G13D (34.14634146); KRAS_G12C,

[0819] EGFR_E746_A750del, KRAS_G12V, KRAS_G13D, EGFR_L861 Q (34.14634146); KRAS_G12C,

[0820] EGFR_E746_A750del, KRAS_G12V, KRAS_G13D, TP53_R273C (34.14634146); KRAS_G12C,

[0821] EGFR_E746_A750del, KRAS_G12V, TP53_R175H (34.14634146); KRAS_G12C,

[0822] EGFR_E746_A750del, KRAS_G12V, TP53_R175H, EGFR_L861 Q (34.14634146); KRAS_G12C,

[0823] EGFR_E746_A750del, KRAS_G12V, TP53_R175H, TP53_R273C (34.14634146); KRAS_G12C,

[0824] EGFR_E746_A750del, KRAS_G12V, TP53_V157F (34.14634146); KRAS_G12C,

[0825] EGFR_E746_A750del, KRAS_G12V, TP53_V157F, EGFR_L861 Q (34.14634146); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_V157F, TP53_R273C (34.14634146); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13C, TP53_R175H (34.14634146); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R273L, KRAS_G13C (34.14634146); KRAS_G12C,

[0826] EGFR_L858R, KRAS_G12A, KRAS_G13C, KRAS_G13D (34.14634146); KRAS_G12C,

[0827] EGFR_L858R, KRAS_G12D (34.14634146); KRAS_G12C, EGFR_L858R, KRAS_G12D, EGFR_L861 Q (34.14634146); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R175H

[0828] (34.14634146); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R175H, EGFR_L861 Q

[0829] (34.14634146); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R175H, TP53_R273C

[0830] (34.14634146); KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273C (34.14634146);

[0831] KRAS_G12C, EGFR_L858R, KRAS_G12D, TP53_R273C, EGFR_L861 Q (34.14634146);

[0832] KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L, KRAS_G13C (34.14634146);

[0833] KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_V157F (34.14634146); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_V157F, EGFR_L861 Q (34.14634146); KRAS_G12C, KRAS_G12V, KRAS_G12A,

[0834] TP53_V157F, TP53_R273C (34.14634146); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_V157F,

[0835] KRAS_G13C (34.14634146); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R158L,

[0836] KRAS_G13C (33.84146341); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273L

[0837] (33.84146341); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273L, EGFR_L861 Q

[0838] (33.84146341); KRAS_G12C, EGFR_E746_A750del, KRAS_G12V, TP53_R273L, TP53_R273C

[0839] (33.84146341); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R158L, KRAS_G13D

[0840] (33.84146341); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R158L, TP53_V157F

[0841] (33.84146341); KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M, KRAS_G13C

[0842] (33.84146341); KRAS_G12C, EGFR_L858R, KRAS_G12A, KRAS_G13C, TP53_R175H

[0843] (33.84146341); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R158L, TP53_V157F

[0844] (33.84146341); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R273L, KRAS_G13C

[0845] (33.84146341); KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13D (33.84146341);

[0846] KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13D, EGFR_L861 Q (33.84146341); KRAS_G12C, KRAS_G12V, KRAS_G12A, KRAS_G13D, TP53_R273C (33.84146341); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R175H (33.84146341); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R175H, EGFR_L861 Q (33.84146341); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R175H, TP53_R273C

[0847] (33.84146341); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13C, KRAS_G13D

[0848] (33.84146341); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13C, TP53_R175H

[0849] (33.84146341); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, KRAS_G13C (33.53658537); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13C (33.53658537); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13C, EGFR_L861 Q (33.53658537); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13C, TP53_R273C (33.53658537); KRAS_G12A, TP53_R273L, KRAS_G13D (32.92682927); KRAS_G12C, KRAS_G12D, KRAS_G12A,

[0850] EGFR_T790M, TP53_R158L (32.92682927); KRAS_G12C, KRAS_G12D, KRAS_G12A,

[0851] KRAS_G13C, KRAS_G13D (32.92682927); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R158L, TP53_V157F (32.92682927); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L, TP53_R273L

[0852] (32.92682927); KRAS_G12C, KRAS_G12V, KRAS_G12A (32.92682927); KRAS_G12C, KRAS_G12V, KRAS_G12A, EGFR_L861 Q (32.92682927); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R273C

[0853] (32.92682927); KRAS_G12C, KRAS_G12V, KRAS_G12A, TP53_R273C, EGFR_L861 Q

[0854] (32.92682927); KRAS_G12C, KRAS_G 12 V, KRAS_G 13C , KRAS_G13D, TP53_R175H

[0855] (32.92682927); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13C (32.92682927);

[0856] KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13C, EGFR_L861 Q (32.92682927); KRAS_G12C,

[0857] KRAS_G12V, TP53_R158L, KRAS_G13C, TP53_R273C (32.92682927); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13D, TP53_R175H (32.92682927); KRAS_G12C, KRAS_G12V, TP53_R158L,

[0858] TP53_V157F, TP53_R273L (32.92682927); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R273L, KRAS_G13C (32.92682927); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_R158L (32.62195122); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C, TP53_R175H (32.62195122); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273L, KRAS_G13C (32.62195122); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, KRAS_G13D (32.62195122); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, TP53_V157F (32.62195122); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13D (32.62195122); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13D, EGFR_L861 Q (32.62195122); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, KRAS_G13D, TP53_R273C (32.62195122); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_V157F (32.62195122); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_V157F, EGFR_L861 Q (32.62195122); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_V157F, TP53_R273C (32.62195122); KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M, TP53_R175H (32.62195122);

[0859] KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M, TP53_R273L (32.62195122);

[0860] KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R158L (32.62195122); KRAS_G12C,

[0861] EGFR_L858R, KRAS_G12A, TP53_R158L, EGFR_L861 Q (32.62195122); KRAS_G12C,

[0862] EGFR_L858R, KRAS_G12A, TP53_R158L, TP53_R273C (32.62195122); KRAS_G12C,

[0863] EGFR_L858R, KRAS_G12A, TP53_R273L, TP53_R175H (32.62195122); KRAS_G12C,

[0864] EGFR_L858R, KRAS_G12A, TP53_V157F (32.62195122); KRAS_G12C, EGFR_L858R,

[0865] KRAS_G12A, TP53_V157F, EGFR_L861 Q (32.62195122); KRAS_G12C, EGFR_L858R,

[0866] KRAS_G12A, TP53_V157F, TP53_R273C (32.62195122); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M, KRAS_G13D (32.62195122); KRAS_G12C, KRAS_G12D, KRAS_G12A,

[0867] EGFR_T790M, TP53_V157F (32.62195122); KRAS_G12C, KRAS_G12D, KRAS_G12A,

[0868] TP53_R158L, KRAS_G13D (32.62195122); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13C

[0869] (32.62195122); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13C, EGFR_L861 Q

[0870] (32.62195122); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13C, TP53_R273C

[0871] (32.62195122); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13D, TP53_R175H

[0872] (32.62195122); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_V157F, KRAS_G13D

[0873] (32.62195122); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_V157F, TP53_R175H

[0874] (32.62195122); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273L, KRAS_G13D

[0875] (32.62195122); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273L, TP53_R175H

[0876] (32.62195122); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13C, KRAS_G13D

[0877] (32.62195122); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13C, TP53_R175H

[0878] (32.62195122); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, KRAS_G13D

[0879] (32.31707317); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_V157F

[0880] (32.31707317); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C (32.31707317);

[0881] KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C, EGFR_L861 Q (32.31707317);

[0882] KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13C, TP53_R273C (32.31707317); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R158L, TP53_R175H (32.31707317);

[0883] KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R158L, TP53_R273L (32.31707317);

[0884] KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, KRAS_G13D (32.31707317);

[0885] KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, TP53_R175H (32.31707317);

[0886] KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, TP53_R273L (32.31707317);

[0887] KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R175H (32.31707317); KRAS_G12C,

[0888] EGFR_L858R, EGFR_E746_A750del, TP53_R175H, EGFR_L861 Q (32.31707317); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R175H, TP53_R273C (32.31707317); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R273L (32.31707317); KRAS_G12C, EGFR_L858R,

[0889] EGFR_E746_A750del, TP53_R273L, EGFR_L861 Q (32.31707317); KRAS_G12C, EGFR_L858R,

[0890] EGFR_E746_A750del, TP53_R273L, TP53_R273C (32.31707317); KRAS_G12C, EGFR_L858R,

[0891] KRAS_G12A, KRAS_G13D (32.31707317); KRAS_G12C, EGFR_L858R, KRAS_G12A, KRAS_G13D,

[0892] EGFR_L861 Q (32.31707317); KRAS_G12C, EGFR_L858R, KRAS_G12A, KRAS_G13D, TP53_R273C (32.31707317); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F, KRAS_G13C

[0893] (32.31707317); KRAS_G12C, KRAS_G12D, KRAS_G12A, KRAS_G13C, TP53_R175H

[0894] (32.31707317); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R273L, KRAS_G13C

[0895] (32.31707317); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_V157F, KRAS_G13D

[0896] (32.31707317); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L (32.31707317);

[0897] KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L, EGFR_L861 Q (32.31707317);

[0898] KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R158L, TP53_R273C (32.31707317);

[0899] KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273L, KRAS_G13D (32.31707317);

[0900] KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273L, TP53_R175H (32.31707317);

[0901] KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_V157F, TP53_R273L (32.31707317); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_V157F (32.31707317); KRAS_G12C, KRAS_G12V, TP53_R158L,

[0902] TP53_V157F, EGFR_L861 Q (32.31707317); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_V157F, TP53_R273C (32.31707317); KRAS_G12C, KRAS_G12V, TP53_V157F, KRAS_G13C (32.31707317);

[0903] KRAS_G12C, KRAS_G12V, TP53_V157F, KRAS_G13C, EGFR_L861 Q (32.31707317); KRAS_G12C, KRAS_G12V, TP53_V157F, KRAS_G13C, TP53_R273C (32.31707317); KRAS_G12C, KRAS_G12V,

[0904] TP53_V157F, KRAS_G13D, TP53_R175H (32.31707317); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G12A (32.01219512); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R158L (32.01219512); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53 R158L, EGFR L861 Q (32.01219512); KRAS G12C, EGFR E746 A750del, KRAS G12D,

[0905] TP53_R158L, TP53_R273C (32.01219512); KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M (32.01219512); KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M, EGFR_L861 Q (32.01219512); KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_T790M,

[0906] TP53_R273C (32.01219512); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R175H (32.01219512); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R175H, EGFR_L861 Q (32.01219512); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R175H, TP53_R273C

[0907] (32.01219512); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R273L (32.01219512);

[0908] KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R273L, EGFR_L861 Q (32.01219512);

[0909] KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R273L, TP53_R273C (32.01219512);

[0910] KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13C, KRAS_G13D (32.01219512); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M, TP53_R175H (32.01219512);

[0911] KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M, TP53_R273L (32.01219512);

[0912] KRAS_G12C, KRAS_G12D, KRAS_G12A, KRAS_G13C (32.01219512); KRAS_G12C, KRAS_G12D, KRAS_G12A, KRAS_G13C, EGFR_L861 Q (32.01219512); KRAS_G12C, KRAS_G12D, KRAS_G12A, KRAS_G13C, TP53_R273C (32.01219512); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R158L, TP53_R175H (32.01219512); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R158L, TP53_R273L (32.01219512); KRAS_G12C, KRAS_G12V, KRAS_G13C, KRAS_G13D (32.01219512); KRAS_G12C, KRAS_G12V, KRAS_G13C, KRAS_G13D, EGFR_L861 Q (32.01219512); KRAS_G12C, KRAS_G12V, KRAS_G13C, KRAS_G13D, TP53_R273C (32.01219512); KRAS_G12C, KRAS_G12V, KRAS_G13C, TP53_R175H (32.01219512); KRAS_G12C, KRAS_G12V, KRAS_G13C, TP53_R175H, EGFR_L861 Q (32.01219512); KRAS_G12C, KRAS_G12V, KRAS_G13C, TP53_R175H, TP53_R273C (32.01219512); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13D (32.01219512); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13D, EGFR_L861 Q (32.01219512); KRAS_G12C, KRAS_G12V, TP53_R158L, KRAS_G13D, TP53_R273C (32.01219512); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R175H (32.01219512); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R175H, EGFR_L861 Q (32.01219512); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R175H, TP53_R273C (32.01219512); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R273L, KRAS_G13D (32.01219512); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R273L, TP53_R175H (32.01219512); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_R175H (31.70731707); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_R273L (31.70731707); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D, TP53_R175H (31.70731707); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273L, KRAS_G13D (31.70731707); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, TP53_R175H (31.70731707); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_V157F, TP53 R273L (31.70731707); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del (31.70731707); KRAS_G12C, EGFR_L858R,

[0913] EGFR_E746_A750del, EGFR_L861 Q (31.70731707); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M (31.70731707); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, EGFR_L861 Q (31.70731707); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, EGFR_T790M, TP53_R273C (31.70731707); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R273C (31.70731707); KRAS_G12C, EGFR_L858R, EGFR_E746_A750del, TP53_R273C, EGFR_L861 Q (31.70731707); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R158L, KRAS_G13C (31.70731707); KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13C, TP53_R175H (31 .70731707); KRAS_G12C, EGFR_L858R,

[0914] TP53_R158L, TP53_R273L, KRAS_G13C (31 .70731707); KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13C, KRAS_G13D (31.70731707); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M (31.70731707); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M, EGFR_L861 Q (31.70731707); KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_T790M, TP53_R273C (31.70731707); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R158L (31.70731707);

[0915] KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R158L, EGFR L861 Q (31.70731707);

[0916] KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R158L, TP53_R273C (31.70731707); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_V157F, TP53_R175H (31.70731707); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_V157F, TP53_R273L (31 .70731707); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13D (31.70731707); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13D, EGFR_L861 Q (31.70731707); KRAS_G12C, KRAS_G12V, EGFR_T790M, KRAS_G13D, TP53_R273C (31.70731707); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R175H (31.70731707); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R175H, EGFR_L861 Q (31.70731707); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R175H, TP53_R273C (31.70731707); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_V157F (31.70731707);

[0917] KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_V157F, EGFR_L861 Q (31.70731707); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_V157F, TP53 R273C (31.70731707);

[0918] KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273L (31.70731707); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273L, EGFR_L861 Q (31 .70731707); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273L, TP53_R273C (31.70731707); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13C (31.70731707); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13C, EGFR_L861 Q (31.70731707); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13C, TP53_R273C (31.70731707); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13D, TP53_R175H

[0919] (31.70731707); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M (31.40243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, EGFR L861 Q (31.40243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, EGFR_T790M, TP53_R273C (31.40243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D (31.40243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D, EGFR_L861 Q (31 .40243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, KRAS_G13D, TP53_R273C (31.40243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_V157F (31.40243902); KRAS_G12C,

[0920] EGFR_E746_A750del, KRAS_G12D, TP53_V157F, EGFR_L861 Q (31.40243902); KRAS_G12C,

[0921] EGFR_E746_A750del, KRAS_G12D, TP53_V157F, TP53_R273C (31.40243902); KRAS_G12C,

[0922] EGFR_L858R, KRAS_G12A (31.40243902); KRAS_G12C, EGFR_L858R, KRAS_G12A, EGFR_L861 Q (31.40243902); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R273C

[0923] (31.40243902); KRAS_G12C, EGFR_L858R, KRAS_G12A, TP53_R273C, EGFR_L861 Q

[0924] (31.40243902); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F, KRAS_G13D

[0925] (31.40243902); KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13C, TP53_R175H

[0926] (31.40243902); KRAS_G12C, EGFR_L858R, TP53_V157F, TP53_R273L, KRAS_G13C

[0927] (31.40243902); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R158L, KRAS_G13C

[0928] (31.40243902); KRAS_G12C, KRAS_G12D, KRAS_G12A, KRAS_G13D, TP53_R175H

[0929] (31.40243902); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R273L, KRAS_G13D

[0930] (31.40243902); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_V157F (31.40243902);

[0931] KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_V157F, EGFR_L861 Q (31 .40243902); KRAS_G12C,

[0932] KRAS_G12D, KRAS_G12A, TP53_V157F, TP53_R273C (31.40243902); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_V157F, KRAS_G13C (31 .40243902); KRAS_G12C, KRAS_G12V, EGFR_T790M,

[0933] TP53_R273L (31 .40243902); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273L,

[0934] EGFR_L861 Q (31 .40243902); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273L,

[0935] TP53_R273C (31 .40243902); KRAS_G12C, KRAS_G12V, TP53_V157F, KRAS_G13D (31 .40243902); KRAS_G12C, KRAS_G12V, TP53_V157F, KRAS_G13D, EGFR_L861 Q (31.40243902); KRAS_G12C,

[0936] KRAS_G12V, TP53_V157F, KRAS_G13D, TP53_R273C (31.40243902); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R175H (31.40243902); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R175H,

[0937] EGFR_L861 Q (31.40243902); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R175H, TP53_R273C

[0938] (31.40243902); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273L, TP53_R175H

[0939] (31.09756098); KRAS_G12C, EGFR_L858R, EGFR_T790M, KRAS_G13C, KRAS_G13D

[0940] (31.09756098); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_V157F, KRAS_G13C

[0941] (31.09756098); KRAS_G12C, EGFR_L858R, KRAS_G13C, KRAS_G13D, TP53_R175H

[0942] (31.09756098); KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13C (31.09756098);

[0943] KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13C, EGFR_L861 Q (31.09756098);

[0944] KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13C, TP53_R273C (31.09756098);

[0945] KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F, TP53_R175H (31.09756098);

[0946] KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F, TP53_R273L (31 .09756098); KRAS_G12C,

[0947] EGFR_L858R, TP53_R273L, KRAS_G13C, KRAS_G13D (31 .09756098); KRAS_G12C,

[0948] KRAS_G12D, KRAS_G12A, KRAS_G13D (31.09756098); KRAS_G12C, KRAS_G12D, KRAS_G12A, KRAS_G13D, EGFR_L861 Q (31.09756098); KRAS_G12C, KRAS_G12D, KRAS_G12A,

[0949] KRAS_G13D, TP53_R273C (31.09756098); KRAS_G12C, KRAS_G12D, TP53_R158L, KRAS_G13C, KRAS_G13D (31.09756098); KRAS_G12C, KRAS_G12V, KRAS_G13C (31.09756098); KRAS_G12C, KRAS_G12V, KRAS_G13C, EGFR_L861 Q (31.09756098); KRAS_G12C, KRAS_G12V, KRAS_G13C, TP53_R273C (31 .09756098); KRAS_G12C, KRAS_G12V, KRAS_G13C, TP53_R273C, EGFR_L861 Q (31.09756098); KRAS_G12C, KRAS_G12V, KRAS_G13D, TP53_R175H (31.09756098);

[0950] KRAS_G12C, KRAS_G12V, KRAS_G13D, TP53_R175H, EGFR_L861 Q (31.09756098); KRAS_G12C, KRAS_G12V, KRAS_G13D, TP53_R175H, TP53_R273C (31.09756098); KRAS_G12C, KRAS_G12V, TP53_R158L (31.09756098); KRAS_G12C, KRAS_G12V, TP53_R158L, EGFR_L861 Q (31.09756098); KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273C (31.09756098);

[0951] KRAS_G12C, KRAS_G12V, TP53_R158L, TP53_R273C, EGFR_L861 Q (31.09756098);

[0952] KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R273L (31.09756098); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R273L, EGFR_L861 Q (31.09756098); KRAS_G12C, KRAS_G12V, TP53_V157F,

[0953] TP53_R273L, TP53_R273C (31.09756098); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R158L, KRAS_G13C (30.79268293); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R175H (30.79268293); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R175H, EGFR_L861 Q (30.79268293); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R175H, TP53_R273C (30.79268293); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273L (30.79268293); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273L, EGFR_L861 Q (30.79268293); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273L, TP53_R273C

[0954] (30.79268293); KRAS_G12C, EGFR_L858R, EGFR_T790M, KRAS_G13C, TP53_R175H

[0955] (30.79268293); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R158L, KRAS_G13D

[0956] (30.79268293); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R158L, TP53_V157F

[0957] (30.79268293); KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_R273L, KRAS_G13C

[0958] (30.79268293); KRAS_G12C, EGFR_L858R, TP53_R158L, KRAS_G13D, TP53_R175H

[0959] (30.79268293); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_R273L, KRAS_G13D

[0960] (30.79268293); KRAS_G12C, EGFR_L858R, TP53_R273L, KRAS_G13C, TP53_R175H

[0961] (30.79268293); KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13C (30.79268293);

[0962] KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13C, EGFR_L861 Q (30.79268293);

[0963] KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13C, TP53_R273C (30.79268293);

[0964] KRAS_G12C, KRAS_G12D, EGFR_T790M, KRAS_G13C, KRAS_G13D (30.79268293);

[0965] KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_V157F, KRAS_G13C (30.79268293);

[0966] KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R273L, TP53_R175H (30.79268293); KRAS_G12C, KRAS_G12V, EGFR_T790M (30.79268293); KRAS_G12C, KRAS_G12V, EGFR_T790M, EGFR_L861 Q (30.79268293); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273C (30.79268293); KRAS_G12C, KRAS_G12V, EGFR_T790M, TP53_R273C, EGFR_L861 Q

[0967] (30.79268293); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS G13D (30.79268293);

[0968] KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13D, EGFR_L861 Q (30.79268293); KRAS_G12C, KRAS_G12V, TP53_R273L, KRAS_G13D, TP53_R273C (30.79268293); KRAS_G12C, KRAS_G12V, TP53_R273L, TP53_R175H (30.79268293); KRAS_G12C, KRAS_G12V, TP53_R273L, TP53_R175H, EGFR_L861 Q (30.79268293); KRAS_G12C, KRAS_G12V, TP53_R273L, TP53_R175H, TP53_R273C (30.79268293); EGFR_L858R, EGFR_E746_A750del, KRAS_G12V, KRAS_G12D, KRAS_G13C (30.48780488); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, EGFR_T790M, KRAS_G13C (30.48780488); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, KRAS_G13C, KRAS_G13D (30.48780488); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, KRAS_G13C, TP53_R175H (30.48780488); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_V157F, KRAS_G13C (30.48780488); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D (30.48780488); KRAS_G12C,

[0969] EGFR_E746_A750del, KRAS_G12D, EGFR_L861 Q (30.48780488); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53 R273C (30.48780488); KRAS_G12C, EGFR_E746_A750del, KRAS_G12D, TP53_R273C, EGFR_L861 Q (30.48780488); KRAS_G12C,

[0970] EGFR_L858R, EGFR_T790M, TP53_R158L, TP53_R175H (30.48780488); KRAS_G12C,

[0971] EGFR_L858R, EGFR_T790M, TP53_R158L, TP53_R273L (30.48780488); KRAS_G12C,

[0972] EGFR_L858R, KRAS_G13C, KRAS_G13D (30.48780488); KRAS_G12C, EGFR_L858R,

[0973] KRAS_G13C, KRAS_G13D, EGFR_L861 Q (30.48780488); KRAS_G12C, EGFR_L858R,

[0974] KRAS_G13C, KRAS_G13D, TP53_R273C (30.48780488); KRAS_G12C, EGFR_L858R,

[0975] TP53_R158L, TP53_R273L, TP53 R175H (30.48780488); KRAS_G12C, EGFR_L858R,

[0976] TP53_R158L, TP53_V157F (30.48780488); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F,

[0977] EGFR_L861 Q (30.48780488); KRAS_G12C, EGFR_L858R, TP53_R158L, TP53_V157F,

[0978] TP53_R273C (30.48780488); KRAS_G12C, EGFR_L858R, TP53_V157F, KRAS_G13D, TP53_R175H

[0979] (30.48780488); KRAS_G12C, EGFR_L858R, TP53_V157F, TP53_R273L, KRAS_G13D

[0980] (30.48780488); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R158L, KRAS_G13D

[0981] (30.48780488); KRAS_G12C, KRAS_G12D, EGFR_T790M, TP53_R158L, TP53 V157F (30.48780488); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R175H (30.48780488);

[0982] KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R175H, EGFR_L861 Q (30.48780488);

[0983] KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R175H, TP53_R273C (30.48780488); KRAS_G12C,

[0984] KRAS_G12D, KRAS_G12A, TP53_R273L (30.48780488); KRAS_G12C, KRAS_G12D, KRAS_G12A,

[0985] TP53_R273L, EGFR_L861 Q (30.48780488); KRAS_G12C, KRAS_G12D, KRAS_G12A,

[0986] TP53_R273L, TP53_R273C (30.48780488); KRAS_G12C, KRAS_G12D, TP53_R158L, KRAS_G13C,

[0987] TP53_R175H (30.48780488); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_R273L, KRAS_G13C

[0988] (30.48780488); KRAS_G12C, KRAS_G12D, TP53_R158L, TP53_V157F, KRAS_G13D

[0989] (30.48780488); KRAS_G12C, KRAS_G12D, TP53_V157F, KRAS_G13C, KRAS_G13D

[0990] (30.48780488); KRAS_G12C, KRAS_G12V, TP53_V157F (30.48780488); KRAS_G12C, KRAS_G12V,

[0991] TP53_V157F, EGFR_L861 Q (30.48780488); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R273C

[0992] (30.48780488); KRAS_G12C, KRAS_G12V, TP53_V157F, TP53_R273C, EGFR_L861 Q

[0993] (30.48780488); EGFR_L858R, KRAS_G12V, KRAS_G12D, KRAS_G12A, KRAS_G13C

[0994] (30.18292683); KRAS_G12C, EGFR_E746_A750del, KRAS_G12A, TP53_R273L, KRAS_G13C

[0995] (30.18292683); KRAS_G12C, EGFR_L858R, EGFR_T790M, KRAS_G13C (30.18292683);

[0996] KRAS_G12C, EGFR_L858R, EGFR_T790M, KRAS_G13C, EGFR_L861 Q (30.18292683);

[0997] KRAS_G12C, EGFR_L858R, EGFR_T790M, KRAS_G13C, TP53_R273C (30.18292683);

[0998] KRAS_G12C, EGFR_L858R, EGFR_T790M, TP53_V157F, KRAS_G13D (30.18292683);

[0999] KRAS_G12C, EGFR_L858R, KRAS_G13C, TP53_R175H (30.18292683); KRAS_G12C,

[1000] EGFR_L858R, KRAS_G13C, TP53_R175H, EGFR_L861 Q (30.18292683); KRAS_G12C,

[1001] EGFR_L858R, KRAS_G13C, TP53_R175H, TP53_R273C (30.18292683); KRAS_G12C,

[1002] EGFR_L858R, TP53_R158L, KRAS_G13D (30.18292683); KRAS_G12C, EGFR_L858R,

[1003] TP53_R158L, KRAS_G13D, EGFR_L861 Q (30.18292683); KRAS_G12C, EGFR_L858R,

[1004] TP53_R158L, KRAS_G13D, TP53_R273C (30.18292683); KRAS_G12C, EGFR_L858R,

[1005] TP53_R273L, KRAS_G13C (30.18292683); KRAS_G12C, EGFR_L858R, TP53_R273L,

[1006] KRAS_G13C, EGFR_L861Q (30.18292683); KRAS_G12C, EGFR_L858R, TP53_R273L,

[1007] KRAS_G13C, TP53_R273C (30.18292683); KRAS_G12C, EGFR_L858R, TP53_V157F,

[1008] TP53_R273L, TP53_R175H (30.18292683); KRAS_G12C, KRAS_G12D, EGFR_T790M,

[1009] KRAS_G13C, TP53_R175H (30.18292683); KRAS_G12C, KRAS_G12D, EGFR_T790M,

[1010] TP53_R273L, KRAS_G13C (30.18292683); KRAS_G12C, KRAS_G12D, KRAS_G12A (30.18292683);

[1011] KRAS_G12C, KRAS_G12D, KRAS_G12A, EGFR_L861 Q (30.18292683); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R273C (30.18292683); KRAS_G12C, KRAS_G12D, KRAS_G12A, TP53_R273C, EGFR_L861 Q (30.18292683); KRAS_G12C, KRAS_G12D, TP53_R158L, KRAS_G13C

[1012] (30.18292683); KRAS_G12C, KRAS_G12D, TP53_R158L, KRAS_G13C, EGFR_L861 Q

[1013] (30.18292683); KRAS_G12C, KRAS_G12D, TP53_R158L, KRAS_G13C, TP53_R273C

[1014] (30.18292683); KRAS_G12C, KRAS_G12V, KRAS_G13D (30.18292683); KRAS_G12C, KRAS_G12V, KRAS_G13D, EGFR_L861 Q (30.18292683); KRAS_G12C, KRAS_G12V, KRAS_G13D, TP53_R273C

[1015] (30.18292683); KRAS_G12C, KRAS_G12V, KRAS_G13D, TP53_R273C, EGFR_L861 Q

[1016] (30.18292683); KRAS_G12C, KRAS_G12V, TP53_R175H (30.18292683); KRAS_G12C,

[1017] KRAS_G12V, TP53_R175H, EGFR_L861 Q (30.18292683); KRAS_G12C, KRAS_G12V,

[1018] TP53_R175H, TP53_R273C (30.18292683); KRAS_G12C, KRAS_G12V, TP53_R175H,

[1019] TP53_R273C, EGFR_L861 Q (30.18292683).

[1020] Each of the antigens in the plurality of antigens may be between 8-35 amino acids in length. Each of the antigens in the plurality of antigens may be between 8-10 amino acids in length. When each of the antigens are 8-10 amino acids in length, they may preferentially bind to MHC class I molecules. Each of the antigens in the plurality of antigens may be between 13-27 amino acids in length. When the antigens are between 13-27 amino acids in length, they may preferentially bind MHC class 2 molecules. Advantageously, when the antigens are between 13-27 amino acids in length, they may be processed and recognised by both MHC class I and MHC class II molecules. The antigens may be up to 35 amino acids in length, or up to 30 amino acids in length. It will be appreciated that if the length of the antigen sequence is increased this will take up more of the packaging limit of the viral vector, and the viral vector may not be able to express as many different antigens as compared to when shorter antigen sequences are used. The vector may comprise coding sequences for a plurality of neoantigens, each neoantigen having the same length. The vector may comprise coding sequences for a plurality of neoantigens, each neoantigen comprising a mutated residue or set of residues in the centre of the peptide or as close as possible to the centre of the peptide given the location of the mutated residue(s) in the protein, and normal residues either side of the mutated residue(s). For example, each neoantigen may be 25 amino acids in length, with a single mutated residue or deletion at position 13, and normal residues at positions 1-12 and 14-25. The same principles can be applied to any peptide length as described herein. When the mutated residue(s) are less than 12 amino acids from the start of the protein, the neoantigen may comprise the first 25 amino acids of the protein (including the mutated residues). When the mutated residue(s) are less than 12 amino acids from the end of the protein, the neoantigen may comprise the last 25 amino acids of the protein (including the mutated residues). When the vectors comprise a TAA, the vector may comprise the full coding sequence of the protein, or an immunogenic portion thereof. The TAA sequence in the vector may comprise multiple immunogenic epitopes, or the TAA sequence may comprise a single epitope. When the TAA sequence comprises an immunogenic portion of the full coding sequence, the sequence may contain a single particularly immunogenic epitope.

[1021] The plurality of antigens comprising antigens associated with mutations in at least two genes selected from TP53, KRAS and EGFR may be concatenated, without separation by a linker sequence. Advantageously, concatenating antigen sequences maximises the amount of nucleotide sequence that can be inserted into a viral vector before the packaging limit is reached. Concatenated means that the coding sequence of the second antigen begins directly after the coding sequence of the first antigen. The order of the antigens within the plurality of antigens may be optimised to reduce the presentation of junction epitopes that may stimulate an immune response. Junction epitopes are novel epitopes that span the junction between a pair of antigen sequences in the vector. Junction epitopes have the potential to be presented by HLA class I or class II alleles of a patient and stimulate a CD8 or CD4 T cell response, respectively. Such reactions are often undesirable because T cells reactive to the junction epitopes have no therapeutic benefit and may diminish the immune response to the selected therapeutic epitopes of the plurality of antigens associated with mutations by antigenic competition. Thus, the vector may comprise coding sequences for a plurality of antigens and optionally TAAs, immediately adjacent to each other, where the order of the coding sequences is such that the number of junction epitopes for the particular set of neoantigens / TAAs is the lowest possible for this set of coding sequences. Junction epitopes are peptide sequences that are encoded by sequences comprising a junction between coding sequences of two adjacent neoantigens / TAAs, where the peptide sequence is determined to be immunogenic. A peptide sequence may be determined to be immunogenic experimentally (e.g. using an ELISPOT assay) or by predicting the MHC binding affinity and / or likelihood of MHC presentation of the peptide using any tool known in the art (such as e.g. NetMHCpan-4.1 and / or NetMHCIIpan-4.1). For example, the number of junction epitopes associated with a pair of neoantigen / TAA sequences may be determined by predicting H LA binding affinity for all peptides of a predetermined length or set of lengths (e.g. 8 to 11 amino acids peptides) that include a junction, and identifying the top x percent predicted binding affinity peptides as likely immunogenic peptides. The top x % may be the top 0.5% and 1 % for MHC class I and MHC class II prediction, respectively. The top x % may be assessed over all tested peptides over all pairs of sequences possible given a set of neoantigen / TAA sequences.

[1022] In embodiments, a vector, nucleic acid or composition as described herein comprises a molecular adjuvant peptide or sequence coding for a molecular adjuvant. The molecular adjuvant may be a portion of the MHC class Il-associated invariant chain (li). The portion may comprise part or all of the transmembrane domain of the MHC class Il-associated invariant chain (li-TMD). The portion may comprise the sequence of SEQ ID NO: 88. An exemplary sequence encoding this sequence is provided as SEQ ID NO: 89. The molecular adjuvant may be a peptide fused to an antigen peptide. The peptide may be fused on the N-terminal side of an antigen peptide. Thus, a vector or nucleic acid as described herein may comprise a sequence coding for a molecular adjuvant, such as a portion of the MHC class Il-associated invariant chain, immediately N-terofa sequence coding for a plurality of antigens as described herein. Li has been shown to act as a molecular adjuvant in viral vector vaccines. Further, linkage of antigen to li in adenoviral vectors has been shown by the present inventors to improve cell-mediated immunity and immunogenicity induced by recombinant adenovirus vaccines of the disclosure.

[1023] The sequences coding for the plurality of antigens may comprise sequences coding for the following antigens in the following order, or any continuous subset of the following sequences that maintains said order: EGFR_L858R, NY-ESO-1 , TP53_G245C, TP53_R273L, TP53_R273C, TP53_R248W, TP53_V157F, TP53_R175H, KRAS_G13D, KRAS_G12A, KRAS_G12C, KRAS_G12V, TP53_Y234C, KRAS_G13C, TP53_R273H, TP53_R248Q, TP53_R158L, EGFR_E746_A750del, EGFR_T790M, TP53_Y220C, KRAS_G12R, KRAS_G12D, and EGFR_L861Q (e.g. v1 inserts as described herein). Alternatively, the sequences coding for the plurality of antigens may comprise sequences coding for the following antigens in the following order, or any continuous subset of the following sequences that maintains said order: EGFR_L858R, NY-ESO-1 , TP53_G245C, TP53_R273L, TP53_R273C, TP53_R248W, TP53_V157F, TP53_R175H, KRAS_G13D, KRAS_G12A, KRAS_G12C, KRAS_G12V, TP53_Y234C, KRAS_G13C, TP53_R273H, TP53_R248Q, TP53_R158L, EGFR_E746_A750del, EGFR_T790M, TP53_Y220C, KRAS_G12R, KRAS_G12D, EGFR_L861 Q, and MUC1 (e.g. v2 inserts as described herein). Alternatively, the sequences coding for the plurality of antigens may comprise sequences coding for the following antigens in the following order, or any continuous subset of the following sequences that maintains said order: TP53_G245C, TP53_R273L, TP53_R273C, TP53_R248W, TP53_V157F, TP53_R175H, KRAS_G13D, KRAS_G12A, KRAS_G12C, KRAS_G12V, TP53_Y234C, KRAS_G13C, TP53_R273H, TP53_R248Q, TP53_R158L, EGFR_E746_A750del, EGFR_T790M, TP53_Y220C, KRAS_G12R, EGFR_L861Q, KRAS_G12D, and EGFR_L858R (e.g. v3 inserts as described herein). Alternatively, the sequences coding for the plurality of antigens may comprise sequences coding for the following antigens in the following order, or any continuous subset of the following sequences that maintains said order: TP53_G245C, TP53_R273L, TP53_R273C, TP53_R248W, TP53_V157F, TP53_R175H, KRAS_G13D, KRAS_G12A, KRAS_G12C, KRAS_G12V, TP53_Y234C, KRAS_G13C, TP53_R273H, TP53_R248Q, TP53_R158L, MUC1 ,

[1024] EGFR_E746_A750del, EGFR_T790M, TP53_Y220C, KRAS_G12R, EGFR_L861 Q, KRAS_G12D, and EGFR_L858R (e.g. v4 inserts as described herein). Any continuous subset of the above sequence of antigens is also envisaged, such as e.g. any set of 5, 10 or 15 antigens selected from the above, in the above order. In any of the above, the sequences of the antigens may be as provided in SEQ ID NOs: 1-24 (Table 3). Corresponding coding sequences are provided in Table 3 as SEQ ID NO: 25-48. Thus, the vectors described herein may comprise coding sequences for a plurality of antigens in any of the orders specified above, where the coding sequences of the antigens specified are as described in Table 3 (SEQ ID NO.: 25-48) or codon optimised versions thereof. Instead or in addition to this, the vectors and nucleic acids described herein may encode for a polypeptide that when translated comprises sequences of antigens in any of the orders specified above, where the sequence of the antigens specified are as described in Table 3 (SEQ ID NOs: 1-24). For example, the polypeptide may comprise the following sequences in the following order (or any continuous subset thereof): SEQ ID NO.: 4, SEQ ID NO.: 23, SEQ ID NO.: 13, SEQ ID NO.: 12, SEQ ID NO.: 19, SEQ ID NO.: 20. SEQ ID NO.: 15, SEQ ID NO.: 18, SEQ ID NO.: 10, SEQ ID NO.: 8, SEQ ID NO.: 7, SEQ ID NO.: 6, SEQ ID NO.: 21 , SEQ ID NO.: 5, SEQ ID NO.: 16, SEQ ID NO.: 17, SEQ ID NO.: 14, SEQ ID NO.: 2, SEQ ID NO.: 1 , SEQ ID NO.: 22, SEQ ID NO.: 9, SEQ ID NO.: 11 , and SEQ ID NO.: 3. As another example, the polypeptide may comprise the following sequences in the following order (or any continuous subset thereof): SEQ ID NO.: 4, SEQ ID NO.: 23, SEQ ID NO.: 13, SEQ ID NO.: 12, SEQ ID NO.: 19, SEQ ID NO.: 20, SEQ ID NO.: 15, SEQ ID NO.: 18, SEQ ID NO.: 10, SEQ ID NO.: 8, SEQ ID NO.: 7, SEQ ID NO.: 6, SEQ ID NO.: 21 , SEQ ID NO.: 5, SEQ ID NO.: 16, SEQ ID NO.: 17, SEQ ID NO.: 14, SEQ ID NO.: 2, SEQ ID NO.: 1 , SEQ ID NO.: 22, SEQ ID NO.: 9, SEQ ID NO.: 11 , SEQ ID NO.: 3, and SEQ ID NO.: 24. As another example, the polypeptide may comprise the following sequences in the following order (or any continuous subset thereof): SEQ ID NO.: 13, SEQ ID NO.: 12, SEQ ID NO.: 19, SEQ ID NO.: 20, SEQ ID NO.: 15, SEQ ID NO.: 18, SEQ ID NO.: 10, SEQ ID NO.: 8, SEQ ID NO.: 7, SEQ ID NO.: 6, SEQ ID NO.: 21 , SEQ ID NO.: 5, SEQ ID NO.: 16, SEQ ID NO.: 17, SEQ ID NO.: 14, SEQ ID NO.: 2, SEQ ID NO.: 1 , SEQ ID NO.: 22, SEQ ID NO.: 9, SEQ ID NO.: 3, SEQ ID NO.: 11 , and SEQ ID NO.: 4. As another example, the polypeptide may comprise the following sequences in the following order (or any continuous subset thereof): SEQ ID NO.: 13, SEQ ID NO.: 12, SEQ ID NO.: 19, SEQ ID NO.: 20, SEQ ID NO.: 15, SEQ ID NO.: 18, SEQ ID NO.: 10, SEQ ID NO.: 8, SEQ ID NO.: 7, SEQ ID NO.: 6, SEQ ID NO.: 21 , SEQ ID NO.: 5, SEQ ID NO.: 16, SEQ ID NO.: 17, SEQ ID NO.: 14, SEQ ID NO.: 24, SEQ ID NO.: 2, SEQ ID NO.: 1 , SEQ ID NO.: 22, SEQ ID NO.: 9, SEQ ID NO.: 3, SEQ ID NO.: 11 , and SEQ ID NO.: 4. The vector or nucleic acid as described herein may comprise the following sequences or codon optimised versions thereof in the following order (or any continuous subset thereof): SEQ ID NO.: 28, SEQ ID NO.: 47, SEQ ID NO.: 37, SEQ ID NO.: 36, SEQ ID NO.: 43, SEQ ID NO.: 44, SEQ ID NO.: 39, SEQ ID NO.: 42, SEQ ID NO.: 34, SEQ ID NO.: 32, SEQ ID NO.: 31 , SEQ ID NO.: 30, SEQ ID NO.: 45, SEQ ID NO.: 29, SEQ ID NO.: 40, SEQ ID NO.: 41 , SEQ ID NO.: 38, SEQ ID NO.: 26, SEQ ID NO.: 25, SEQ ID NO.: 46, SEQ ID NO.: 33, SEQ ID NO.: 35, and SEQ ID NO.: 27. The vector or nucleic acid as described herein may comprise the following sequences or codon optimised versions thereof in the following order (or any continuous subset thereof): SEQ ID NO.: 28, SEQ ID NO.: 47, SEQ ID NO.: 37, SEQ ID NO.: 36, SEQ ID NO.: 43, SEQ ID NO.: 44, SEQ ID NO.: 39, SEQ ID N...

Claims

Claims1. An immunogenic composition comprising a nucleic acid molecule encoding a plurality of antigens or cells presenting said plurality of antigens, wherein the antigens of said plurality of antigens are associated with mutations in at least two genes selected from TP53, KRAS and EGFR.

2. The immunogenic composition according to claim 1 , wherein the plurality of antigens comprise at least one antigen associated with a mutation in each of TP53, KRAS and EGFR.

3. The immunogenic composition according to claim 1 or claim 2, wherein the plurality of antigens comprises antigens associated with at least 5, at least 7, at least 9, at least 10, at least 11 , at least 18 antigens, between 5 and 30, between 10 and 30, between 15 and 25, or about 22 different mutations.

4. The immunogenic composition according to any one of the preceding claims, wherein the plurality of antigens are associated with mutations selected from: EGFR_T790M, EGFR_E746_A750del, EGFR_L861 Q, EGFR_L858R, KRAS_G13C, KRAS_G12V, KRAS_G12C, KRAS_G12A, KRAS_G12R, KRAS_G13D, KRAS_G12D, TP53_R273L, TP53_G245C, TP53_R158L, TP53_V157F, TP53_R273H, TP53_R248Q, TP53_R175H, TP53_R273C, TP53_R248W, TP53_Y234C, TP53_Y220C, or wherein the plurality of antigens comprise mutations selected from: TP53_R175H, KRAS_G12V, KRAS_G12D, EGFR_L858R, TP53_Y220C, KRAS_G12C, EGFR_L858R, EGFR_T709V, TP53_G105V, EGFR_746_750del, EGFR_747_751del, EGFR_T790M, TP53_R248W, TP53_G245S, EGFR_E746_A750del, EGFR_H773L, EGFR_V774M, TP53_P152L, TP53_M237I.

5. The immunogenic composition according to any one of the preceding claims, wherein the plurality of antigens further comprise one or more tumour associated antigens, or immunogenic portions thereof, or wherein the cells further present one or more peptides from one or more tumour associated antigens.

6. The immunogenic composition according to claim 5, wherein the one or more tumour- associated antigens are selected from: MUC1 and NY-ESO-1 , and / or wherein the nucleic acid molecule further encodes NY-ESO-1 and / or an immunogenic portion of MUC1 .

7. The immunogenic composition according to any preceding claim, wherein the plurality of antigens comprise antigens associated with each of the following mutations: EGFR_T790M, EGFR_E746_A750del, EGFR_L861 Q, EGFR_L858R, KRAS_G13C, KRAS_G12V, KRAS_G12C, KRAS_G12A, KRAS_G12R, KRAS_G13D, KRAS_G12D, TP53_R273L, TP53_G245C, TP53_R158L, TP53_V157F, TP53_R273H, TP53_R248Q, TP53_R175H, TP53_R273C, TP53_R248W, TP53_Y234C, and TP53_Y220C.

8. The immunogenic composition according to any one of the preceding claims, wherein the composition comprises a vector comprising a nucleic acid molecule encoding the plurality of antigens.

9. The immunogenic composition according to claim 8, wherein the vector is a DNA viral vector, optionally a ChAdOx vector, optionally a ChAdOx2 vector.

10. The immunogenic composition according to claim 8, wherein the vector is an mRNA nanoparticle, optionally an mRNA lipid nanoparticle.

11. The immunogenic composition according to any one of the preceding claims, wherein the immunogenic composition comprises a nucleic acid and each antigen of the plurality of antigens associated with mutations comprises a sequence of 9 to 35 amino acids, optionally 25 amino acids in length, or wherein the immunogenic composition comprises antigen presenting cells that have been pulsed with the plurality of antigens, each antigen of the antigens associated with a mutation represented as a peptide of 9 to 35 amino acids, optionally 25 amino acids in length; and / or wherein each antigen of the plurality of antigens associated with mutations comprises a mutated residue or deletion in the centre of the peptide or the closest position to the centre of the peptide possible based on the position of the mutated residue or deletion in the protein, and / or wherein each antigen of the plurality of antigens associated with mutations comprises a sequence of 25 amino acids in length and the mutated reside is at position 8, 9, 10, 11 , 12, 13, 14, or 15, optionally wherein the mutated residue is at position 13 or the closest position to position 13 possible based on the position of the mutated residue in the protein.

12. The immunogenic composition according to any preceding claim, wherein each mutation is independently selected from an amino acid substitution, a single or multiple amino acid insertion or deletion, or delin; and / or wherein a mutation is a coding mutation in an exon of the sequence coding for TP53, KRAS or EGFR.

13. The immunogenic composition according to any one of the preceding claims, wherein the nucleic acid molecule comprises coding sequences for at least two antigens of the plurality of antigens that are concatenated, without separation by linker sequences, and / or wherein the nucleic acid comprises coding sequences for a plurality of antigens, including antigens associated with mutations and optionally tumour associated antigens or immunogenic portions thereof, immediately adjacent to each other.

14. The immunogenic composition according to any one of the preceding claims, wherein the nucleic acid molecule comprises concatenated coding sequences for all the antigens of the plurality of antigens, without separation by a linker sequence.

15. The immunogenic composition according to any one of the preceding claims, wherein the nucleic acid comprises coding sequences for the plurality of antigens, in an order such that the predicted number of epitopes comprising sequences from two adjacent antigens is the lowest possible given the antigens included in the vector.

16. The immunogenic composition according to any one of the preceding claims, wherein the plurality of antigens that are associated with mutations, have amino acid sequences selected from: w. LGICLTSTVQLIMQLMPFGCLLDYV (SEQ ID NO.: 1); x. EGEKVKIPVAIKTSPKANKEILDEA (SEQ ID NO.: 2); y. QHVKITDFGLAKQLGAEEKEYHAEG (SEQ ID NO.: 3); z. KTPQHVKITDFGRAKLLGAEEKEYH (SEQ ID NO.: 4); aa. MTEYKLVVVGAGCVGKSALTIQLIQ (SEQ ID NO.: 5); bb. MTEYKLVVVGAVGVGKSALTIQLIQ (SEQ ID NO.: 6); cc. MTEYKLVVVGACGVGKSALTIQLIQ (SEQ ID NO.: 7); dd. MTEYKLVVVGAAGVGKSALTIQLIQ (SEQ ID NO.: 8); ee. MTEYKLVVVGARGVGKSALTIQLIQ (SEQ ID NO.: 9); ff. MTEYKLVVVGAGDVGKSALTIQLIQ (SEQ ID NO.: 10); gg. MTEYKLVVVGADGVGKSALTIQLIQ (SEQ ID NO.: 11); hh. SGNLLGRNSFEVLVCACPGRDRRTE (SEQ ID NO.: 12); ii. HYNYMCNSSCMGCMNRRPILTIITL (SEQ ID NO.: 13); jj. WVDSTPPPGTRVLAMAIYKQSQHMT (SEQ ID NO.: 14); kk. LWVDSTPPPGTRFRAMAIYKQSQHM (SEQ ID NO.: 15);II. SGNLLGRNSFEVHVCACPGRDRRTE (SEQ ID NO.: 16); mm. YMCNSSCMGGMNQRPILTIITLEDS (SEQ ID NO.: 17); nn. YKQSQHMTEVVRHCPHHERCSDSDG (SEQ ID NO.: 18); oo. SGNLLGRNSFEVCVCACPGRDRRTE (SEQ ID NO.: 19); pp. YMCNSSCMGGMNWRPILTIITLEDS (SEQ ID NO.: 20); qq. PPEVGSDCTTIHCNYMCNSSCMGGM (SEQ ID NO.: 21); and rr. DRNTFRHSVVVPCEPPEVGSDCTTI (SEQ ID NO.: 22).

17. The immunogenic composition according to any one of the preceding claims, wherein the nucleic acid comprises a sequence encoding the following amino acid sequence(s) or the cells present one or more peptides derived from the following amino acid sequence(s): a. MQAEGRGTGGSTGDADGPGGPGIPDGPGGNAGGPGEAGATGGRGPRGAGAARASGPGG GAPRGPHGGAASGLNGCCRCGARGPESRLLEFYLAMPFATPMEAELARRSLAQDAPPLPV PGVLLKEFTVSGNILTIRLTAADHRQLQLSISSCLQQLSLLMWITQCFLPVFLAQPPSGQRR (SEQ ID NO.: 23); and / or b. STAPPAHGVTSAPDTRPAPGSTAPP (SEQ ID NO.: 24).

18. The immunogenic composition according to any one of the preceding claims, wherein the nucleic acid comprises one or more nucleic acid sequences selected from: a. CTGGGCATCTGCCTCACCTCCACCGTGCAGCTCATCATGCAGCTCATGCCCTTCGGCTG CCTCCTGGACTATGTC (SEQ ID NO.: 25); b. GAAGGTGAGAAAGTTAAAATTCCCGTCGCTATCAAGACATCTCCGAAAGCCAACAAGGAA ATCCTCGATGAAGCC (SEQ ID NO.: 26); c. CAGCATGTCAAGATCACAGATTTTGGGCTGGCCAAACAGCTGGGTGCGGAAGAGAAAGA ATACCATGCAGAAGGA (SEQ ID NO.: 27);> d. AAAACACCGCAGCATGTCAAGATCACAGATTTTGGGCGGGCCAAACTGCTGGGTGCGGA AGAGAAAGAATACCAT (SEQ ID NO.: 28);e. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTGGTTGCGTAGGCAAGAGTGCCTTGACG ATACAGCTAATTCAG (SEQ ID NO.: 29); f. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTGTTGGCGTAGGCAAGAGTGCCTTGACG ATACAGCTAATTCAG (SEQ ID NO.: 30); g. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTTGTGGCGTAGGCAAGAGTGCCTTGACG ATACAGCTAATTCAG (SEQ ID NO.: 31); h. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTGCTGGCGTAGGCAAGAGTGCCTTGACG ATACAGCTAATTCAG (SEQ ID NO.: 32); i. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTCGTGGCGTAGGCAAGAGTGCCTTGACG ATACAGCTAATTCAG (SEQ ID NO.: 33); j. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTGGTGACGTAGGCAAGAGTGCCTTGACG ATACAGCTAATTCAG (SEQ ID NO.: 34); k. ATGACTGAATATAAACTTGTGGTAGTTGGAGCTGATGGCGTAGGCAAGAGTGCCTTGACG ATACAGCTAATTCAG (SEQ ID NO.: 35); l. AGTGGTAATCTACTGGGACGGAACAGCTTTGAGGTGCTTGTTTGTGCCTGTCCTGGGAG AGACCGGCGCACAGAG (SEQ ID NO.: 36); m. CACTACAACTACATGTGTAACAGTTCCTGCATGGGCTGCATGAACCGGAGGCCCATCCTC ACCATCATCACACTG (SEQ ID NO.: 37); n. TGGGTTGATTCCACACCCCCGCCCGGCACCCGCGTCCTCGCCATGGCCATCTACAAGCA GTCACAGCACATGACG (SEQ ID NO.: 38); o. CTGTGGGTTGATTCCACACCCCCGCCCGGCACCCGCTTCCGCGCCATGGCCATCTACAA GCAGTCACAGCACATG (SEQ ID NO.: 39); p. AGTGGTAATCTACTGGGACGGAACAGCTTTGAGGTGCATGTTTGTGCCTGTCCTGGGAG AGACCGGCGCACAGAG (SEQ ID NO.: 40); q. TACATGTGTAACAGTTCCTGCATGGGCGGCATGAACCAGAGGCCCATCCTCACCATCATC ACACTGGAAGACTCC (SEQ ID NO.: 41); r. TACAAGCAGTCACAGCACATGACGGAGGTTGTGAGGCACTGCCCCCACCATGAGCGCTG CTCAGATAGCGATGGT (SEQ ID NO.: 42); s. AGTGGTAATCTACTGGGACGGAACAGCTTTGAGGTGTGTGTTTGTGCCTGTCCTGGGAG AGACCGGCGCACAGAG (SEQ ID NO.: 43); t. TACATGTGTAACAGTTCCTGCATGGGCGGCATGAACTGGAGGCCCATCCTCACCATCATC ACACTGGAAGACTCC (SEQ ID NO.: 44); u. CCGCCTGAGGTTGGCTCTGACTGTACCACCATCCACTGCAACTACATGTGTAACAGTTCC TGCATGGGCGGCATG (SEQ ID NO.: 45); and v. GACAGAAACACTTTTCGACATAGTGTGGTGGTGCCCTGTGAGCCGCCTGAGGTTGGCTC TGACTGTACCACCATC (SEQ ID NO.: 46); or alternative versions thereof that encode the same amino acid sequences, optionally codon optimised versions thereof.

19. The immunogenic composition according to any one of the preceding claims, wherein the nucleic acid comprises a nucleic acid sequence selected from: SEQ ID NO: 93, 92, 82, 86, 49, 51 , 61 , 63, 52, 54, 64, 66, 82, 86, 84, 94, optionally wherein the nucleic acid comprises a nucleic acid sequence selected from: SEQ ID NO: 93, 92, 82, 86.

20. The immunogenic composition according to any one of the preceding claims, wherein the nucleic acid comprise a sequence that encodes a molecular adjuvant or the compositioncomprises a molecular adjuvant, and / or wherein the nucleic acid comprises a sequence that encodes a fusion of a molecular adjuvant and the plurality of antigens or the composition comprises a fusion of a molecular adjuvant and the plurality of antigens, optionally wherein the molecular adjuvant is a peptide comprising a human CD74 invariant chain transmembrane domain.21 . A vector comprising a nucleic acid molecule encoding a plurality of antigens that are associated with mutations in at least two genes selected from TP53, KRAS and EGFR, optionally wherein the vector has the features of any of claims 1 to 20.

22. An isolated nucleic acid molecule or molecules comprising a sequence encoding a vector according to claim 12.

23. An isolated nucleic acid molecule or set of nucleic acid molecules encoding a plurality of antigens that are associated with mutations in at least two genes selected from TP53, KRAS and EGFR, optionally wherein the vector has the features of any of claims 1 to 22.

24. An immunogenic composition according to any of claims 1 to 20 or a vector according to claim 21 or a nucleic acid molecule according to claim 22, for use in a method of preventing lung cancer or lung cancer recurrence in a subject.

25. The composition, vector or nucleic acid for use according to claim 24, wherein the cancer is lung adenocarcinoma, and / or wherein the subject is a subject who has been diagnosed as being at risk of developing lung cancer, wherein the subject has been diagnosed as having lung adenocarcinoma in situ (AIS), wherein the subject has been diagnosed as having minimally invasive adenocarcinoma (MIA), or wherein the subject that has been diagnosed as having stage 1a or 1 b lung cancer that has been resected, and / or wherein the subject is in remission from lung cancer, or the subject does not have lung cancer that is detectable by low-dose CT scanning.

26. The vector, composition or nucleic acid for use according to any one of claims 24 or 25, wherein the subject has a history of smoking and / or the subject has a chronic lung condition and / or the subject has been diagnosed as having one or more indeterminate pulmonary nodules.

27. The vector, composition or nucleic acid for use according to any one of claims 23 to 25, wherein the vector, composition or nucleic acid is administered intramuscularly, and / or wherein the vector, composition or nucleic acid is administered as a plurality of doses, optionally between 2 and 4 doses, and / or wherein the vector, composition or nucleic acid is administered as a plurality of doses comprising a first dose, a second dose administered between 4 and 16 weeks after administration of a first dose, optionally a third dose is administered between 6 and 12 months after administration of the first dose, and optionally a fourth dose is administered between 12 and 24 months after administration of the first dose, and / or wherein administration of the vector, composition or nucleic acid is associated with a reduction in the risk of recurrence or new primary lung cancer in a subject.

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