Combined drug containing Anti-EGFR antibody or fragment thereof

Abstract

Provided are a product and method for preventing or treating cancer by combining an anti-EGFR antibody or a fragment (for example, an antigen-binding fragment) thereof and a taxane drug, and related applications.

Description

Combination drugs containing anti-EGFR antibodies or fragments thereof

[0001] Citation of Related Applications

[0002] This application claims priority to Chinese Patent Application No. 202410260119.6 filed on March 7, 2024, the entire contents of which are incorporated herein by reference in their entirety and for all purposes. Technical Field

[0003] The present application relates to the field of biopharmaceuticals, and more specifically, to products, methods, and related applications of combining anti-EGFR antibodies or fragments thereof (such as antigen-binding fragments) with taxanes for preventing or treating cancer. Background Art

[0004] Cancer refers to a broad class of diseases characterized by abnormal cell differentiation and proliferation, uncontrolled growth, invasiveness, and metastasis. Unregulated cell division can lead to the formation of malignant tumors or cells that invade adjacent tissues and potentially metastasize to distant parts of the body via the lymphatic system or bloodstream. Cancer development is a complex, multifactorial, multi-step process encompassing three stages: carcinogenesis, promotion, and progression. Cancer is closely linked to smoking, infection, occupational exposure, environmental pollution, an unhealthy diet, and genetic factors. Cancer encompasses many types, generally categorized as primary and secondary. Based on the organ site of origin, cancer can be divided into various types, including lung cancer, stomach cancer, breast cancer, nasopharyngeal cancer, liver cancer, intestinal cancer, and prostate cancer. Based on the tissue system of origin, cancer can be divided into digestive system cancer, respiratory system cancer, genitourinary system cancer, and hematologic system cancer. Based on the body site of origin, cancer can be divided into head and neck cancer, chest cancer, abdominal cancer, and pelvic cancer. Based on the cell of origin, cancer can be divided into three main types: adenocarcinoma, squamous cell carcinoma, and undifferentiated carcinoma. Each cancer has varying incidence and severity.

[0005] Lung cancer has the highest morbidity and mortality rates in China and worldwide. Clinical symptoms are often insidious, with cough, sputum production, hemoptysis, and weight loss as the primary manifestations. Radiographic findings primarily include pulmonary nodules and masses. Most patients are diagnosed at an advanced stage, resulting in a low five-year survival rate. The disease burden is significant and poses a serious threat to Chinese health. The etiology and pathogenesis of lung cancer remain unclear. Approximately 85-90% of lung cancers are caused by active or passive smoking, but there is also evidence linking them to occupational carcinogens (such as asbestos, arsenic, chromium, nickel, and polycyclic aromatic hydrocarbons), air pollution, ionizing radiation, diet and physical activity, and genetic and genomic alterations. Data from 2020 show that lung cancer has become the second most common malignant tumor worldwide (22.4 per 100,000 population) and the most fatal. Approximately 2.207 million new cases of lung cancer were reported worldwide in 2020 (Sung et al., 2021). Lung cancer is the most common cancer in men and the second most common cancer in women in China. In 2020, the incidence of lung cancer in China was approximately 34.8 cases per 100,000 population, with approximately 816,000 new cases (Liu Zongchao et al., 2021). Lung cancer can be divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) based on its histological characteristics. Non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer, accounting for approximately 87% of all lung cancers, of which approximately 40% are adenocarcinomas, 25%–30% are squamous cell carcinomas, and 10%–15% are large cell carcinomas (Yu and He, 2013).

[0006] Tyrosine phosphorylation of the intracellular region of EGFR activates second messenger transduction, inducing the activation of extracellular signals (kinases Erk1 and Erk2) through the MAPK pathway; activating Akt through the PI3K pathway; and activating signal transducers and transcriptional activators of STAT3 and STAT5 through JAK2.

[0007] Currently, EGFR monoclonal antibodies have not been approved or recommended for use in NSCLC by authoritative academic guidelines. Pemetrexed or cetuximab alone are ineffective in second-line treatment of NSCLC. The median OS of the cetuximab-pemetrexed combination regimen was 10.3 m [95% CI: 7.5, 16.8]; the median OS of sequential treatment with pemetrexed and cetuximab was 3.5 m [95% CI: 2.8, 11.7], P = 0.046 (BMC Cancer. 2014 Jan 4; 14:5). The efficacy of EGFR monoclonal antibody combined with chemotherapy in NSCLC is also poor. Although necitumumab combined with gemcitabine and cisplatin has been approved for lung cancer indications, the NCCN Guidelines deleted the recommendation of this therapy due to efficacy, toxicity and cost issues (Lancet Oncology, 2015, 16(7):763-774). In 2015, the NCCN Guidelines deleted the relevant recommendation of cetuximab (first-line therapy of cetuximab / cisplatin / vinorelbine (category 2B), believing that the benefit of cetuximab / cisplatin / vinorelbine regimen is very slight, it is a difficult-to-administer regimen, and its tolerability is worse than other regimens (Lancet 2009; 373:1525-1531). Randomized controlled trials have revealed that panitumumab combined with standard treatment (pemetrexed + platinum) has no benefit in NSCLC, and the data are more supportive of standard treatment (Clinical Lung Cancer). Cancer,2015,16(6):447-456).

[0008] Advanced NSCLC with positive driver gene disease is primarily treated with targeted therapy. Approved or included in the guidelines are inhibitors of EGFR, ALK, ROS1, BRAF V600E, NTRK, and MET14 (Chinese Society of Clinical Oncology Guidelines Working Committee, 2022). For patients with positive driver gene disease who have failed targeted therapy, platinum-based chemotherapy is the preferred treatment option, with docetaxel serving as a standard of care after failure of targeted therapy and platinum-based regimens. For patients with negative driver gene disease, PD-1 / PD-L1 inhibitors, either alone or in combination with platinum-based regimens, are the preferred treatment options. However, if patients progress or relapse after immunotherapy and platinum-based therapy, treatment options are limited, and single-agent chemotherapy remains the primary treatment, but overall efficacy is suboptimal. According to the 2022 CSCO guidelines, docetaxel is the standard second-line treatment for negative driver gene disease and the third-line standard treatment for positive driver gene disease, both receiving a Grade I recommendation (Chinese Society of Clinical Oncology Guidelines Working Committee, 2022). Docetaxel alone has an ORR of only approximately 10%, with a median progression-free survival (mPFS) of approximately 3 months and a median overall survival (mOS) of approximately 10 months (Horn et al., 2017; Rittmeyer et al., 2017; Barlesi et al., 2018; Wu et al., 2019; Zhou et al., 2022). Therefore, there is an urgent clinical need for treatment of non-small cell lung cancer (NSCLC) after failure of previous first-line therapy, particularly squamous cell NSCLC (sqNSCLC), and especially driver gene-negative sqNSCLC. Therefore, it is crucial to develop more effective drugs targeting these patients, particularly sqNSCLC, to precisely treat them. More specifically, if anti-EGFR antibodies can be developed and combined with other lung cancer therapies, especially non-small cell lung cancer therapies, to achieve better treatment effects for non-small cell lung cancer (NSCLC) after failure of previous first-line treatment, especially squamous cell non-small cell lung cancer (sqNSCLC) after failure of previous first-line treatment, and especially driver gene-negative squamous cell non-small cell lung cancer (sqNSCLC) after failure of previous first-line treatment, such as enhancing tumor remission, reducing the likelihood or frequency of recurrence, prolonging survival time, and reducing toxic side effects, these patients will benefit.

[0009] CN103772504A (the entire contents of which are incorporated herein by reference for all purposes) discloses a series of anti-EGFR antibodies or antigen-binding portions thereof, wherein the sequence of the heavy chain CDR1 is selected from the sequence shown in SEQ ID NO: 1 and SEQ ID NO: 39 or a derivative thereof, the sequence of the CDR2 is the sequence shown in SEQ ID NO: 4 or a derivative thereof, and the sequence of the CDR3 is selected from the sequence shown in SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 40 or a derivative thereof; the sequence of the light chain CDR1 is the sequence shown in SEQ ID NO: 11 or a derivative thereof, the sequence of the CDR2 is the sequence shown in SEQ ID NO: 12 or a derivative thereof, and the sequence of the CDR3 is selected from the sequence shown in SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 41 or a derivative thereof (the SEQ ID NO numbers in this paragraph are the SEQ ID NO numbers in CN103772504A).

[0010] CN107773755A (the entire contents of which are incorporated herein by reference and for all purposes) discloses an injectable formulation of an EGFR antibody having a heavy chain with a sequence as shown in SEQ ID NO: 1 and a light chain with a sequence as shown in SEQ ID NO: 2 (the SEQ ID NO number in this paragraph is the SEQ ID NO number in CN107773755A).

[0011] CN115025053A (the entire contents of which are incorporated herein by reference for all purposes) discloses a composition containing docetaxel-containing albumin nanoparticles. The composition comprises docetaxel and acid-denatured albumin, which is obtained by denaturing human serum albumin by adjusting its pH by acidification. The composition can be formulated as an injection or a lyophilized powder for injection.

[0012] SUMMARY OF THE INVENTION

[0013] In a first aspect, the present application provides a combination drug for preventing or treating cancer, comprising an anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment) and a taxane drug administered simultaneously or separately.

[0014] In a second aspect, the present application provides use of an anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment) and a taxane drug in the preparation of a drug for preventing or treating cancer.

[0015] In a third aspect, the present application provides the use of anti-EGFR antibodies or fragments thereof (e.g., antigen-binding fragments) and taxanes in the preparation of drugs for preventing or treating second-line or higher-stage squamous cell non-small cell lung cancer that has failed previous first-line treatment, is driver gene-negative, and has high EGFR expression.

[0016] In a fourth aspect, the present application provides a method for preventing or treating cancer, comprising administering an effective amount of an anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment) and a taxane drug to an individual in need thereof.

[0017] In a fifth aspect, the present application provides a combination of an anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment) and a taxane drug for use in preventing or treating cancer.

[0018] In a sixth aspect, the present application provides an anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment) for use in combination with a taxane drug to prevent or treat cancer.

[0019] In a seventh aspect, the present application provides taxanes for use in combination with anti-EGFR antibodies or fragments thereof (eg, antigen-binding fragments) for preventing or treating cancer.

[0020] Detailed Description of the Invention

[0021] The following specific embodiments and examples are intended to better illustrate the contents of this application, but the contents of this application are not limited to the specific embodiments and examples. Those skilled in the art may make non-essential improvements and adjustments to the embodiments based on the above invention, which still fall within the scope of protection of this application.

[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as understood by one of ordinary skill in the art.The abbreviations for amino acid residues are the standard three-letter and / or one-letter codes used in the art to refer to one of the 20 common L-amino acids.

[0023] Although the numerical ranges and parameter approximations shown in the broad scope of this application, the numerical values ​​shown in the specific embodiments are recorded as accurately as possible. However, any numerical value is necessarily contained in a certain error, which is caused by the standard deviation present in their respective measurements. In addition, all ranges disclosed herein should be understood to cover any and all sub-ranges contained therein. For example, a range of "1 to 10" recorded should be considered to include any and all sub-ranges between a minimum of 1 and a maximum of 10 (including endpoints); that is, all sub-ranges starting with a minimum of 1 or greater, such as 1 to 6.1, and sub-ranges terminating with a maximum of 10 or less, such as 5.5 to 10. In addition, any reference referred to as "incorporated herein" should be understood to be incorporated in its entirety.

[0024] As used herein, the term "pharmaceutical composition" refers to a combination of at least one drug and, optionally, a pharmaceutically acceptable carrier or excipient, combined to achieve a specific purpose. The type of pharmaceutically acceptable carrier is not particularly limited, and suitable buffers, stabilizers, surfactants, and the like may be added according to pharmaceutical formulation techniques in the art. The type of pharmaceutically acceptable carrier used will depend, inter alia, on whether the composition of the present application is formulated for oral, nasal, intradermal, subcutaneous, intramuscular, or intravenous administration.

[0025] As used herein, when referring to a "combination" of two or more drugs, the combination product is not limited to a specific product form, as long as it complies with the product form permitted in combination therapy in the medical field. For example, the two or more drugs in the combination can be formulated together, for example, in the form of a pharmaceutical composition. In addition, the combination can also be provided in the form of a drug set, wherein the two or more drugs in the combination are physically separated (for example, in different drug-containing containers) in the drug set. In addition, if the instructions for use of one of the two or more drugs in the combination state the purpose of use in combination with the other drugs in the combination, it is equivalent to using or recommending the combination.

[0026] In a broad sense, "antibody" can refer to an immunoglobulin molecule that can specifically bind to a target via at least one antigen recognition site located in the variable region of the immunoglobulin molecule, and thus encompasses intact antibodies / full-length antibodies, single antibody chains, or any antigen-binding fragments of antibodies. When "antibody" and "antigen-binding fragment" appear in the same context, "antibody" can be understood as the intact antibody relative to the "antigen-binding fragment", and both correspond to the broad concept of antibody.

[0027] A "full-length / intact antibody" refers to a protein comprising at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each heavy chain comprises a heavy chain variable region (abbreviated as VH) and a heavy chain constant region, which consists of three domains: CH1, CH2, and CH3. Each light chain comprises a light chain variable region (abbreviated as VL) and a light chain constant region, which consists of one domain: CL. The VH and VL regions are further subdivided into highly variable regions known as complementarity determining regions (CDRs), interspersed with more conserved regions known as framework regions (FRs). Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxyl-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. These variable regions of the heavy and light chains contain the binding domain that interacts with the antigen. The constant region of an antibody can mediate the binding of an immunoglobulin to the host's tissue or factors, including various cells of the immune system (such as effector cells) and the first component (C1q) of the classical complement system. Chimeric or humanized antibodies are also encompassed in antibodies according to the present application. Full-length / complete antibodies can be antibodies of any type, such as IgD, IgE, IgG, IgA or IgM (or the subclasses described above), but antibodies do not need to belong to any specific class. According to the antibody amino acid sequence of the constant domain of the heavy chain, immunoglobulins can be designated as different classes. Typically, immunoglobulins have five main classes: IgA, IgD, IgE, IgG and IgM, and several of these classes can be further divided into subclasses (isotypes), such as IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2. The heavy chain constant domains corresponding to different immunoglobulin classes are referred to as α, δ, ε, γ and μ, respectively. The subunit structure and three-dimensional structure of different classes of immunoglobulins are well known.

[0028] As used herein, the term "antigen-binding fragment" refers to an antibody fragment such as Fv, Fab, F(ab')2 or Fab', or any fragment that can increase half-life by chemical modification, such as the addition of poly(alkylene) glycols such as polyethylene glycol ("PEGylation") (PEGylated fragments referred to as Fv-PEG, scFv-PEG, Fab-PEG, F(ab')2-PEG or Fab'-PEG) ("PEG" is polyethylene glycol), or by incorporation into liposomes, wherein the fragment has EGFR binding activity. Preferably, the antigen-binding fragment will be composed of or comprise a partial sequence of the heavy chain or light chain variable region of the antibody from which it is derived, the partial sequence being sufficient to retain the same binding specificity and sufficient affinity as the antibody from which it is derived. Such a functional fragment will contain at least 5 amino acids, preferably 10, 15, 25, 50 and 100 consecutive amino acids of the antibody sequence from which it is derived. Examples of antigen-binding fragments include, but are not limited to: (1) a Fab fragment, which can be a monovalent fragment having a VL-CL chain and a VH-CH1 chain; (2) a F(ab')2 fragment, which can be a bivalent fragment having two Fab' fragments connected by a disulfide bridge at the hinge region (i.e., a dimer of Fab'); and (3) an Fv fragment having the VL and VH domains of a single arm of an antibody.

[0029] The complementarity determining regions (CDRs, typically CDR1, CDR2, and CDR3) are the regions in the variable region that have the greatest impact on the affinity and specificity of an antibody. There are several common definitions for VH or VL CDR sequences, including the IMGT, Chothia, and Kabat definitions. For a given antibody variable region sequence, the CDR sequences in the VH and VL sequences can be determined according to the IMGT, Chothia, or Kabat definitions. The CDR definition used in this application adopts the Kabat definition.

[0030] The term "humanized antibody" as used herein means an antibody obtained by grafting CDR sequences derived from another mammalian species, such as a mouse germline, onto human framework sequences. In order to retain binding affinity, some residues of the backbone (called FR) segment may be modified. Humanized antibodies or fragments thereof according to the present application may be prepared by techniques known to those skilled in the art.

[0031] The term "taxane, paclitaxel, or docetaxel albumin nanoparticle drug" as used herein refers to a drug containing nanoparticles comprising taxane, paclitaxel, or docetaxel and albumin (e.g., acid-denatured albumin). The preparation process of this type of drug can refer to the technology disclosed in CN115025053A.

[0032] As used herein, the term "taxane, paclitaxel or docetaxel injection" refers to an injection formulation containing free taxane, paclitaxel or docetaxel that is not bound to albumin.

[0033] The term "unit preparation" used herein refers to the smallest sub-package of each pharmaceutical preparation containing an appropriate amount of active compound, such as a unit preparation in a capsule refers to a capsule, a unit preparation in a tablet refers to a tablet, a unit preparation in an injection refers to an injection, and so on for other types of preparations.

[0034] The terms "effective amount" or "therapeutically effective amount" as used herein are used interchangeably and refer to an amount that brings about a therapeutic effect on a subject, for example, in a subject to which this amount is administered, the symptoms or state of the disease are alleviated, reduced, or eliminated, or the development of the symptoms or state of the disease is delayed or inhibited, compared to a subject not administered this amount.

[0035] The term "EGFR-positive cancer / tumor" as used herein is understood in the conventional sense in the art, generally referring to at least a portion of cancer / tumor cells expressing EGFR. The degree of EGFR positivity of cancer / tumor can be qualitatively, quantitatively or semi-quantitatively analyzed according to a variety of methods in the art. An exemplary method is to perform immunohistochemical analysis on solid tumor samples (such as biopsy or postoperative slices), for example, semi-quantitatively expressed using H-score. H-score can be expressed by the weighted sum of the percentage of cell staining to express EGFR expression in tumor cells: H-score = (3x percentage of strongly stained cells) + (2x percentage of moderately stained cells) + (1x percentage of weakly stained cells). In this application, cancer / tumor with H-Score>0 is defined as "EGFR-positive cancer / tumor", and cancer / tumor with H-Score≥180 is defined as "EGFR-highly expressing cancer / tumor".

[0036] The “driver genes” in this application include EGFR mutation, ALK fusion, ROS1 rearrangement fusion, BRAF V600 mutation, NTRK fusion, MET exon 14 skipping mutation, RET rearrangement, HER2 mutation, KRAS mutation, NRAS mutation, etc.

[0037] Complete remission (CR) means that all target lesions disappear, and the short axis value of any pathological lymph node (regardless of whether it is a target lesion) must be <10mm.

[0038] Partial response (PR) refers to a reduction of at least 30% in the sum of the diameters of all target lesions relative to the baseline total diameter.

[0039] Progressive disease (PD) is defined as an increase of at least 20% in the sum of the diameters of all target lesions, relative to the smallest total diameter of the lesions during the study (including the sum of the lesion diameters at baseline, if that is the smallest value). In addition, in addition to the 20% relative increase in the sum of the diameters, the absolute value of the sum must also increase by at least 5 mm (Note: the appearance of one or more new lesions can also be considered progressive disease).

[0040] Stable disease (SD) refers to the sum of the smallest lesion diameters during the study as a reference. Lesion reduction does not meet the requirements of PR, and lesion increase does not meet the requirements of PD.

[0041] The objective response rate (ORR) is defined as the proportion of complete remission (CR) or partial remission (PR) (i.e., CR+PR) at the best time point, as evaluated by an independent review committee (IRC) according to the Response Evaluation Criteria for Solid Tumors (RECIST v1.1) from the start of study drug to study exit.

[0042] The disease control rate (DCR) is defined as the proportion of patients with CR, PR, or stable disease (SD) (i.e., CR+PR+SD) at the best time point, as evaluated according to the RECIST 1.1 standard, from the start of study drug to study exit.

[0043] Progression-free survival (PFS) was defined as the time from the start of study drug to the date of first documented disease progression (PD) or death, whichever occurred first.

[0044] Overall survival (OS) was defined as the time from the start of study drug to the date of death from any cause.

[0045] In general, the present application provides products, methods, and related applications for the prevention or treatment of cancer using a combination of an anti-EGFR antibody or fragment thereof (e.g., an antigen-binding fragment) and a taxane. In particular, it has been found that the combination of an anti-EGFR antibody or fragment thereof and a taxane for the treatment of NSCLC, particularly non-small cell lung cancer (NSCLC) after failure of previous first-line therapy, particularly squamous cell non-small cell lung cancer (sqNSCLC) after failure of previous first-line therapy, and further, driver gene-negative squamous cell non-small cell lung cancer (sqNSCLC) after failure of previous first-line therapy, exhibits significant advantages in efficacy and other aspects.

[0046] In a first aspect, the present application provides a combination drug for preventing or treating cancer, comprising an anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment) and a taxane drug administered simultaneously or separately.

[0047] In some embodiments, the cancer is an EGFR-positive cancer. In some embodiments, the cancer is a cancer in which tumor cells highly express EGFR.

[0048] In some embodiments, the cancer is selected from lung cancer, gastric cancer, liver cancer, breast cancer, esophageal cancer, kidney cancer, bladder cancer, cervical cancer, colorectal cancer, and lymphoma. In some embodiments, the cancer is lung cancer. In some embodiments, the lung cancer is selected from small cell carcinoma and non-small cell lung cancer. In some embodiments, the lung cancer is non-small cell carcinoma. In some embodiments, the lung cancer is non-small cell lung cancer after failure of a previous first-line treatment. In some embodiments, the lung cancer is squamous cell non-small cell lung cancer (sqNSCLC) after failure of a previous first-line treatment. In some embodiments, the lung cancer is a driver gene-negative squamous cell non-small cell lung cancer after failure of a previous first-line treatment. In some embodiments, the lung cancer is a drug for second-line and above non-small cell lung cancer. In some embodiments, the lung cancer is second-line and above squamous cell non-small cell lung cancer (sqNSCLC). In some embodiments, the lung cancer is second-line and above driver gene-negative squamous cell non-small cell lung cancer (sqNSCLC). In some embodiments, the lung cancer is second-line and above squamous cell non-small cell lung cancer with high EGFR expression, which has failed a previous first-line treatment.

[0049] In some embodiments, the anti-EGFR antibody or fragment thereof is cetuximab, nimotuzumab, panitumumab, necitumumab, or an antigen-binding fragment thereof, or has six CDRs of the heavy and light chains of cetuximab, nimotuzumab, panitumumab, or necitumumab.

[0050] In some embodiments, an anti-EGFR antibody or fragment thereof comprises a heavy chain CDR1 set forth in SEQ ID NO: 1 or SEQ ID NO: 2, a heavy chain CDR2 set forth in SEQ ID NO: 3, and a heavy chain CDR3 set forth in SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6, and / or a light chain CDR1 set forth in SEQ ID NO: 7, a light chain CDR2 set forth in SEQ ID NO: 8, and a light chain CDR3 set forth in SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11. In some embodiments, an anti-EGFR antibody or fragment thereof comprises a heavy chain CDR1 set forth in SEQ ID NO: 1, a heavy chain CDR2 set forth in SEQ ID NO: 3, and a heavy chain CDR3 set forth in SEQ ID NO: 4, and / or a light chain CDR1 set forth in SEQ ID NO: 7, a light chain CDR2 set forth in SEQ ID NO: 8, and a light chain CDR3 set forth in SEQ ID NO: 9. In some embodiments, an anti-EGFR antibody or fragment thereof comprises a heavy chain variable region set forth in SEQ ID NO: 12 and / or a light chain variable region set forth in SEQ ID NO: 13. In some embodiments, the anti-EGFR antibody comprises the heavy chain set forth in SEQ ID NO:14 and / or the light chain set forth in SEQ ID NO:15.

[0051] In some embodiments, the anti-EGFR antibody fragment or fragment thereof can be a single-chain antibody (scFv), a chimeric antibody, a diabody, a scFv-Fc bivalent molecule, a dAb, a Fab fragment, a Fab' fragment, an Fv or a F(ab')2 fragment. In some embodiments, the anti-EGFR antibody is a full-length anti-EGFR antibody. In some embodiments, the anti-EGFR antibody has a human IgG1 heavy chain constant region and / or a human kappa light chain constant region. In some embodiments, the anti-EGFR antibody is a humanized antibody.

[0052] In some embodiments, the taxane is a taxane albumin nanoparticle drug or a taxane injection. In some embodiments, the taxane is a paclitaxel albumin nanoparticle drug or a paclitaxel injection, or a docetaxel albumin nanoparticle drug or a docetaxel injection. In some embodiments, the taxane is a docetaxel albumin nanoparticle drug or a docetaxel injection.

[0053] In some embodiments, the combination is in the form of a pharmaceutical composition in which an anti-EGFR antibody or fragment thereof and a taxane are formulated together.

[0054] In some embodiments, the combination drug is in the form of a pharmaceutical kit, wherein the anti-EGFR antibody or fragment thereof and the taxane are physically separated in the pharmaceutical kit.

[0055] In a second aspect, the present application provides use of an anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment) and a taxane drug in the preparation of a drug for preventing or treating cancer.

[0056] In a third aspect, the present application provides the use of anti-EGFR antibodies or fragments thereof (e.g., antigen-binding fragments) and taxanes in the preparation of drugs for preventing or treating second-line or higher-stage squamous cell non-small cell lung cancer that has failed previous first-line treatment, is driver gene-negative, and has high EGFR expression.

[0057] The second and third aspects of the invention include not only the use of anti-EGFR antibodies or fragments thereof (e.g., antigen-binding fragments) and taxanes in the joint preparation of medicaments for preventing or treating cancer, but also the use of anti-EGFR antibodies or fragments thereof (e.g., antigen-binding fragments) in the preparation of medicaments for preventing or treating cancer in combination with taxanes, and the use of taxanes in the preparation of medicaments for preventing or treating cancer in combination with anti-EGFR antibodies or fragments thereof (e.g., antigen-binding fragments).

[0058] The embodiments and technical features described in the first aspect regarding the anti-EGFR antibody or fragment thereof, taxane drugs, indications, drug forms, etc. are also applicable to the second and third aspects if there is no conflict.

[0059] In a fourth aspect, the present application provides a method for preventing or treating cancer, comprising administering an effective amount of an anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment) and a taxane drug to an individual in need thereof.

[0060] The embodiments and technical features described in the first aspect regarding the anti-EGFR antibody or fragment thereof, taxane drugs, indications, drug forms, etc. are also applicable to the fourth aspect if there is no conflict.

[0061] In some embodiments, the anti-EGFR antibody is administered before, simultaneously with, or after the taxane.

[0062] In some embodiments, the individual is a mammal. In some embodiments, the individual is a human.

[0063] In some embodiments, the anti-EGFR antibody or fragment thereof is administered at a dose of 4 mg / kg to 10 mg / kg. In some embodiments, the anti-EGFR antibody or fragment thereof is administered at a dose of 4 mg / kg, 4.8 mg / kg, 6 mg / kg, 8 mg / kg, 9 mg / kg, or 10 mg / kg. In some embodiments, the anti-EGFR antibody or fragment thereof is administered at a dose of 6 mg / kg or 9 mg / kg.

[0064] In some embodiments, the anti-EGFR antibody or fragment thereof is administered once every 1-4 weeks. In some embodiments, the anti-EGFR antibody or fragment thereof is administered once every 1 week, once every 2 weeks, once every 3 weeks, or once every 4 weeks. In some embodiments, the anti-EGFR antibody or fragment thereof is administered once every 2 weeks or once every 3 weeks.

[0065] In some embodiments, the taxane is administered at a dose of 50-150 mg / m 2 In some embodiments, the taxane is administered at a dose of 50 mg / m 2 , 55mg / m 2 , 60mg / m 2 , 65mg / m 2 , 70mg / m 2 , 75mg / m 2 , 80mg / m 2 , 85mg / m 2 , 90mg / m 2 , 95mg / m 2 , 100mg / m 2 , 105mg / m 2 , 110mg / m 2 , 115mg / m 2 , 120mg / m 2 , 125mg / m 2 , 130mg / m 2 , 135mg / m 2 , 140mg / m 2 , 145mg / m 2 or 150 mg / m 2 In some embodiments, the taxane is administered at a dose of 60 mg / m 2 , 65mg / m 2 , 70mg / m 2 , 75mg / m 2 , 80mg / m 2 , 85mg / m 2 , 90mg / m 2 , 95mg / m2 or 100 mg / m 2 In some embodiments, the taxane is administered at a dose of 75 mg / m 2 or 100 mg / m 2 In some embodiments, the taxane is administered once every 1-4 weeks. In some embodiments, the taxane is administered once a week, once every 2 weeks, once every 3 weeks, or once every 4 weeks. In some embodiments, the taxane is administered once every 2 weeks or once every 3 weeks.

[0066] In some embodiments, the taxane drug is docetaxel albumin nanoparticle drug. In some embodiments, the dosage of docetaxel albumin nanoparticle drug is 50-150 mg / m 2 In some embodiments, the dosage of docetaxel albumin nanoparticles is 50 mg / m 2 , 55mg / m 2 , 60mg / m 2 , 65mg / m 2 , 70mg / m 2 , 75mg / m 2 , 80mg / m 2 , 85mg / m 2 , 90mg / m 2 , 95mg / m 2 , 100mg / m 2 , 105mg / m 2 , 110mg / m 2 , 115mg / m 2 , 120mg / m 2 , 125mg / m 2 , 130mg / m 2 , 135mg / m 2 , 140mg / m 2 , 145mg / m 2 or 150 mg / m 2 In some embodiments, the dosage of docetaxel albumin nanoparticles is 60 mg / m 2 , 65mg / m 2 , 70mg / m 2 , 75mg / m 2 , 80mg / m 2 , 85mg / m 2 , 90mg / m 2 , 95mg / m 2 or 100 mg / m 2In some embodiments, the dosage of docetaxel albumin nanoparticles is 75 mg / m 2 or 100 mg / m 2 In some embodiments, the frequency of administration of docetaxel albumin nanoparticles is once every 1-4 weeks. In some embodiments, the frequency of administration of docetaxel albumin nanoparticles is once every 1 week, once every 2 weeks, once every 3 weeks, or once every 4 weeks. In some embodiments, the frequency of administration of docetaxel albumin nanoparticles is once every 2 weeks or once every 3 weeks.

[0067] In some embodiments, the taxane is docetaxel injection. In some embodiments, the dosage of docetaxel injection is 50-150 mg / m 2 In some embodiments, the dosage of docetaxel injection is 50 mg / m 2 , 55mg / m 2 , 60mg / m 2 , 65mg / m 2 , 70mg / m 2 , 75mg / m 2 , 80mg / m 2 , 85mg / m 2 , 90mg / m 2 , 95mg / m 2 , 100mg / m 2 , 105mg / m 2 , 110mg / m 2 , 115mg / m 2 , 120mg / m 2 , 125mg / m 2 , 130mg / m 2 , 135mg / m 2 , 140mg / m 2 , 145mg / m 2 or 150 mg / m 2 In some embodiments, the dosage of docetaxel injection is 50 mg / m 2 , 55mg / m 2 , 60mg / m 2 , 65mg / m 2 , 70mg / m 2 , 75mg / m 2 , 80mg / m 2 , 85mg / m 2 , 90mg / m 2 , 95mg / m 2or 100 mg / m 2 In some embodiments, the dosage of docetaxel injection is 50 mg / m 2 or 75 mg / m 2 In some embodiments, the frequency of administration of docetaxel injection is once every 1-4 weeks. In some embodiments, the frequency of administration of docetaxel injection is once every 1 week, once every 2 weeks, once every 3 weeks, or once every 4 weeks. In some embodiments, the frequency of administration of docetaxel injection is once every 2 weeks or once every 3 weeks.

[0068] In some embodiments, the treatment methods of the present application comprise: first administering an anti-EGFR antibody or fragment thereof, then administering a taxane, then administering the anti-EGFR antibody or fragment thereof, then administering the taxane after an interval of 1-4 weeks (1 week, 2 weeks, 3 weeks, or 4 weeks), more preferably cycling this administration regimen with a 2-week or 3-week cycle. The above-mentioned dosing regimen is cycled until disease progression, intolerable toxicity, or the patient is assessed to have no benefit from treatment, whichever occurs first.

[0069] In some embodiments, the treatment method of the present application comprises: first administering an anti-EGFR antibody or a fragment thereof at a dose of 6 mg / kg, and then administering a taxane at a dose of 75 mg / m 2 After 2 weeks, anti-EGFR antibody or its fragment was given at a dose of 6 mg / kg, and then taxane was given at a dose of 75 mg / m 2 The administration regimen is cycled for 2 weeks, and the cycle is performed according to the above-mentioned dosing regimen until the disease progresses, the toxicity is intolerable, or the individual is evaluated as not benefiting from the treatment, whichever occurs first.

[0070] In some embodiments, the treatment method of the present application comprises: first administering an anti-EGFR antibody or a fragment thereof at a dose of 6 mg / kg, and then administering docetaxel albumin nanoparticles at a dose of 75 mg / m 2 After 2 weeks, anti-EGFR antibody or its fragment was given at a dose of 6 mg / kg, and then docetaxel albumin nanoparticles were given at a dose of 75 mg / m 2 The administration regimen is cycled for 2 weeks. The cycle is repeated according to the above dosing regimen until the disease progresses, the toxicity cannot be tolerated, or the individual is evaluated as not benefiting from the treatment, whichever occurs first.

[0071] In some embodiments, the treatment method of the present application comprises: first administering an anti-EGFR antibody or a fragment thereof at a dose of 9 mg / kg, and then administering a taxane at a dose of 100 mg / m 2After 3 weeks, anti-EGFR antibody or its fragment was given at a dose of 9 mg / kg, and then taxane drugs were given at a dose of 100 mg / m 2 The administration regimen is cycled for 3 weeks, and the cycle is performed according to the above-mentioned dosing regimen until the disease progresses, the toxicity is intolerable, or the individual is evaluated as not benefiting from the treatment, whichever occurs first.

[0072] In some embodiments, the treatment method of the present application comprises: first administering an anti-EGFR antibody or a fragment thereof at a dose of 9 mg / kg, and then administering docetaxel albumin nanoparticles at a dose of 100 mg / m 2 After 3 weeks, anti-EGFR antibody or its fragment was given at a dose of 9 mg / kg, and then docetaxel albumin nanoparticles were given at a dose of 100 mg / m 2 The administration regimen is cycled for 3 weeks. Cycles are performed according to the above dosing regimen until disease progression, intolerable toxicity, or the individual is assessed to be unable to benefit from treatment, whichever occurs first.

[0073] In some embodiments, the treatment method of the present application comprises: first administering an anti-EGFR antibody or a fragment thereof at a dose of 6 mg / kg, and then administering docetaxel injection at a dose of 60 mg / m 2 After 2 weeks, anti-EGFR antibody or its fragment was given at a dose of 6 mg / kg, and then docetaxel albumin nanoparticles were given at a dose of 60 mg / m 2 The administration regimen is cycled for 2 weeks. The cycle is repeated according to the above dosing regimen until the disease progresses, the toxicity cannot be tolerated, or the individual is evaluated as not benefiting from the treatment, whichever occurs first.

[0074] In some embodiments, the treatment method of the present application comprises: first administering an anti-EGFR antibody or a fragment thereof at a dose of 9 mg / kg, then administering docetaxel injection at a dose of 75 mg / m 2 After 3 weeks, anti-EGFR antibody or its fragment was given at a dose of 9 mg / kg, and then docetaxel albumin nanoparticles were given at a dose of 75 mg / m 2 The administration regimen is cycled for 3 weeks. Cycles are performed according to the above dosing regimen until disease progression, intolerable toxicity, or the individual is assessed to be unable to benefit from treatment, whichever occurs first.

[0075] In a fifth aspect, the present application provides a combination of an anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment) and a taxane drug for use in preventing or treating cancer.

[0076] In a sixth aspect, the present application provides an anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment) for use in combination with a taxane drug to prevent or treat cancer.

[0077] In a seventh aspect, the present application provides taxanes for use in combination with anti-EGFR antibodies or fragments thereof (eg, antigen-binding fragments) for preventing or treating cancer.

[0078] The embodiments and technical features described in all aspects of the first to fourth aspects regarding the anti-EGFR antibody or fragment thereof, taxane drugs, indications, drug forms, administration regimens, etc. are also applicable to the fifth to seventh aspects if there is no conflict.

[0079] Herein (particularly in the Examples), the anti-EGFR antibody having a heavy chain as shown in SEQ ID NO: 14 and a light chain as shown in SEQ ID NO: 15 is named JMT101. For simplicity, JMT101 also refers to the injectable formulation of the antibody in the Examples below, which can be understood from the context.

[0080] The "docetaxel albumin nanoparticle drug" described herein may also be referred to as "docetaxel for injection (albumin-bound)." The docetaxel for injection (albumin-bound) in the examples was prepared using the method of Example 1 using the formulation 1-1 of Example 1 in CN115025053A. Example

[0081] Clinical Research

[0082] A randomized, controlled, open-label, Phase II / III clinical study evaluating the safety, tolerability, and preliminary efficacy of JMT101 injection combined with two docetaxel injection formulations in patients with locally advanced / recurrent or distantly metastatic squamous cell non-small cell lung cancer.

[0083] This study aims to preliminarily evaluate the safety and efficacy of JMT101 in combination with two docetaxel injection formulations in the treatment of second-line and higher (≥2L) EGFR-highly expressed squamous cell lung cancer.

[0084] Trial CDE registration number: CTR20240822

[0085] Study Drug:

[0086] 1. JMT101, specification: 100 mg / 10.0 mL / vial, injection, prepared according to the method described in CN107773755A.

[0087] 2. Docetaxel Injection Preparation A: Docetaxel for injection (albumin-bound) was prepared using the preparation method of Example 1 using the formulation 1-1 in Example 1 of CN115025053A.

[0088] 3. Docetaxel injection preparation B: Docetaxel injection, produced by Jiangsu Hengrui Medicine Co., Ltd., with the trade name of Aisu.

[0089] Trial population:

[0090] Patients with histologically or cytologically confirmed (pathology report required) non-small cell lung cancer, pathological type of squamous cell carcinoma, high EGFR expression (H-Score ≥ 180), and negative expression of other driver genes; patients who have previously received standard first-line treatment and have experienced disease progression or intolerance.

[0091] Study Objectives

[0092] Main research objectives:

[0093] - Preliminary evaluation of the safety and tolerability of JMT101 in combination with two docetaxel injection formulations

[0094] - Primary efficacy endpoints evaluating JMT101 in combination with two docetaxel injection formulations versus docetaxel monotherapy

[0095] Secondary study objectives:

[0096] - Secondary efficacy endpoints evaluating JMT101 in combination with two docetaxel injection formulations

[0097] - Evaluate the safety of JMT101 in combination with two docetaxel injection formulations

[0098] - Evaluate the pharmacokinetic profile of JMT101 in combination with two docetaxel injection formulations

[0099] -Evaluate the correlation between biomarkers and efficacy and safety

[0100] Combination therapy:

[0101] JMT101 combined with docetaxel injection formulation A, or JMT101 combined with docetaxel injection formulation B.

[0102] Initial dosing sequence: JMT101 infusion first, followed by infusion of docetaxel injection formulation A or B.

[0103] Dosage:

[0104] JMT101: 9 mg / kg, Q3W, with one treatment cycle being every 3 weeks.

[0105] Docetaxel injection formulation A: 100 mg / m 2 ,Q3W, every 3 weeks is a treatment cycle.

[0106] Docetaxel injection formulation B: 75 mg / m 2 ,Q3W, every 3 weeks is a treatment cycle.

[0107] Monotherapy:

[0108] Docetaxel injection formulation A: 100 mg / m 2 ,Q3W, every 3 weeks is a treatment cycle.

[0109] Docetaxel injection formulation B: 75 mg / m 2 ,Q3W, every 3 weeks is a treatment cycle.

[0110] This trial consists of a Phase II study (including a safety introduction phase (Stage I) and an efficacy exploration phase (Stage II)) and a Phase III study (a randomized controlled trial (Stage III)). Stage I is the safety introduction phase of the combination therapy, while Stages II and III adopt a randomized, controlled, open-label, multicenter design.

[0111] Security introduction stage (Stage I):

[0112] experimental group

[0113] A "3+3" trial design was used to explore the recommended Phase II dose of JMT101 in combination with docetaxel injection Formulation A in patients with squamous cell non-small cell lung cancer. A 21-day (three-week schedule) DLT observation period followed the first dose of the study drug. If no intolerance was observed during the DLT observation period, subsequent treatment could be continued until the participant experienced disease progression, death, intolerable toxicity, voluntary withdrawal from the trial, or the investigator determined that further treatment was unsuitable (whichever occurred first).

[0114] Three-week regimen: JMT101 was started at 9 mg / kg once every 3 weeks (Q3W), and then decreased to 6 mg / kg Q3W; docetaxel injection formulation A was administered using the clinically recommended dosing regimen (100 mg / m 2 , Q3W).

[0115] The “3+3” dose escalation principle is as follows:

[0116] (1) If none of the three subjects in the starting dose group experienced DLT and there were only three subjects in this dose group, three more subjects would be added.

[0117] (2) If two or more of the three subjects in the starting dose group experienced DLT, the dose group was decreased by one;

[0118] (3) If one of the three subjects in the starting dose group developed DLT, three more subjects were added. If ≥2 / 6 subjects developed DLT, the dose group was reduced by one;

[0119] (4) When the dose group is lowered to a lower level, if there are only 3 subjects in this dose group, 3 more subjects will be added. If there are already 6 subjects in this dose group, the dose escalation trial is terminated.

[0120] Based on the data from the safety introduction phase, a reasonable medication dosage is selected to enter Stage II; if necessary, an SMC meeting is held, and the next step is carried out according to the resolution of the SMC meeting, or the plan is revised (see the SMC charter for specific procedures).

[0121] DLT definition: One or more toxic reactions occurring during the DLT evaluation window (Days 1-21 after the start of study dosing [three-week schedule]) that are judged to be reasonably related (related, probably related, and possibly related) to treatment with JMT101 or docetaxel injection formulation A.

[0122] Docetaxel injection preparation B is a marketed product that has been marketed and used for nearly 20 years in China and abroad and has extensive clinical experience. 75 mg / m2 is used alone or in combination with other drugs. 2 , Q3W are both recommended doses in the instructions. JMT101 is a monoclonal antibody preparation with a different metabolic pathway than docetaxel, and combined use will not affect drug metabolism. Both Docetaxel Injection Formulation A and Docetaxel Injection Formulation B contain docetaxel as their active ingredient. Safety observations for JMT101 combined with Docetaxel Injection Formulation A have already been conducted during the safety introduction phase. Therefore, there is no need to further investigate the safety of JMT101 combined with Docetaxel Injection Formulation B.

[0123] Efficacy exploration stage (Stage II):

[0124] Subjects meeting the eligibility criteria will be randomly assigned in a 1:1:1 ratio into the following three cohorts and receive the corresponding treatment. Each cohort is planned to enroll approximately 30 patients, and the specific enrollment number may be adjusted appropriately based on the progress of the study. After discussion by the SMC, Trial Groups A and B may be designated to use the recommended combination regimen based on preliminary safety data obtained in the Phase I study, or a decision may be made not to initiate or to terminate a trial group early.

[0125] Trial Group A: JMT101 combined with docetaxel injection B for three weeks. The dosage and administration regimen used in the Phase I study to obtain preliminary safety data were used.

[0126] Experimental group B: JMT101 combined with docetaxel injection formulation A for three weeks.

[0127] Group C: Docetaxel injection formulation A was administered using the recommended clinical dosing regimen (100 mg / m 2 , Q3W)

[0128] The above treatment groups continued treatment until the participants experienced disease progression, death, intolerable toxicity, voluntary withdrawal from the trial, or the investigator determined that they were not suitable for further treatment (whichever occurred first).

[0129] Efficacy confirmation stage (Stage III):

[0130] Before entering Stage III, the applicant will communicate with the Center for Drug Evaluation (CDE) of the National Medical Products Administration based on the early clinical research data of this study, and enter Stage III after obtaining the communication results.

[0131] Subjects who met the inclusion criteria were randomly divided into the following two cohorts in a 1:1 ratio according to ECOG (0 vs 1) and received corresponding treatment. Each cohort was planned to enroll approximately 210 cases.

[0132] Trial Group: JMT101 combination regimen. Based on the data from Stages I and II, the trial group will adopt the most effective and safe combination regimen and dosage level among the three Stage II trial groups.

[0133] Control group: docetaxel injection preparation B (75 mg / m 2 , administered once every 3 weeks).

[0134] The above treatment groups continued treatment until the participants experienced disease progression, death, intolerable toxicity, voluntary withdrawal from the trial, or the investigator determined that they were not suitable for further treatment (whichever occurred first).

[0135] Efficacy evaluation

[0136] All participants were assessed for objective anti-tumor efficacy by the investigator and the BIRC according to RECIST v1.1 criteria. Tumor imaging assessments were performed every 6 weeks (±7 days) starting from the date of first dosing until disease progression, death, or voluntary withdrawal from the trial. Investigators could perform additional unplanned tumor assessments based on clinical needs.

[0137] For participants who are first diagnosed with a CR or PR based on the RECIST v1.1 criteria, another imaging examination is required to confirm the result at least 4 weeks later. If the interval between the efficacy confirmation examination date and the next scheduled tumor assessment date is ≤ 4 weeks, the next scheduled tumor assessment will be skipped. Otherwise, the next tumor efficacy assessment will be performed as planned. If the participant discontinues treatment due to non-radiologically confirmed disease progression, imaging assessment will still be required as specified in the protocol until the start of new anti-tumor treatment, radiographic disease progression determined and confirmed by the investigator, voluntary withdrawal from the trial, loss to follow-up, or death (whichever occurs first).

[0138] Safety Assessment

[0139] CTCAE version 5.0 was used to analyze and summarize changes in physical examination, vital signs, ECG, echocardiography, and safety laboratory indicators, and to report the severity, incidence, and correlation of TEAEs and SAEs with the study drug.

[0140] Pharmacokinetic evaluation

[0141] For all participants using JMT101 in Stage I, Stage II, and Stage III, venous blood was collected at the planned time points to detect the serum JMT101 concentration.

[0142] Venous blood was collected at scheduled time points for the determination of plasma docetaxel concentrations from all participants in Stage I, Stage II, and Stage III who received docetaxel injection formulation A or B. Blood samples were also collected for the determination of α-acid glycoprotein (AAG).

[0143] Immunogenicity assessment

[0144] Venous blood will be collected from all participants using JMT101 in Stage I, Stage II, and Stage III at the planned time points. The separated serum samples will first be used for ADA detection of JMT101, and samples confirmed to be ADA positive will be further tested for titer and NAb.

[0145] The sample size for Stage Ⅰ-Ⅱ of this trial was not calculated with statistical assumptions.

[0146] Safety introduction stage (Stage Ⅰ): a maximum of 24 cases will be enrolled.

[0147] Efficacy Exploration Phase (Stage II): Approximately 90 participants will be randomly assigned to three different trial groups in a 1:1:1 ratio. The SMC may decide not to initiate or terminate a trial group early.

[0148] Efficacy confirmation stage (Stage III): Approximately 420 participants were randomly assigned to the experimental group or the control group (SoC (Standard of Care)) in a 1:1 ratio for treatment.

[0149] Statistical considerations:

[0150] 1) Security introduction stage (Stage I)

[0151] Analyze the dataset

[0152] FAS: Based on the basic principles of ITT, all participants who have successfully enrolled and received at least one trial intervention are included. FAS is used for demographic, baseline characteristics, and efficacy analyses.

[0153] SS: Includes all successfully enrolled participants who received at least one trial intervention. SS is used for safety and tolerability analyses. In safety analyses, all participants will be analyzed based on the actual treatment group they received.

[0154] DAS: Includes all participants in the DLT assessment period, participants who have completed the DLT assessment, or participants who have experienced DLT during the DLT assessment period. This analysis set will be used for the analysis and aggregation of DLT events.

[0155] PKCS: Participants who received at least one dose of JMT101 or docetaxel injection formulation A and had at least one post-dose concentration data.

[0156] IS: Participants who have received at least 1 prior JMT101 treatment and have baseline and at least one post-baseline immunogenicity data.

[0157] Demographic and baseline analyses

[0158] Summarize the enrollment, medication, and data set division of each group of participants, and present them using a subject distribution flow chart. List a detailed list of participant data sets.

[0159] Demographic data and baseline characteristics were statistically described. For continuous variables, the number, mean, standard deviation, median, minimum, and maximum values ​​were calculated; for count and rank data, the number and percentage were calculated. Descriptive statistics of the participants' demographic data and baseline characteristics were tabulated.

[0160] Primary Endpoint Analysis

[0161] DLT analysis.

[0162] The incidence of DLTs will be pooled and analyzed across DAS groups.

[0163] Adverse events.

[0164] All AEs were coded using MedDRA. Only TEAEs (TEAEs) occurring on or after the first dose of the trial intervention and no later than 30 days after the last dose were analyzed. Non-TEAEs were not included in the analysis and were simply tabulated. If the onset date / time of an AE was incomplete, it was determined to be a TEAE based on the available information. If the onset date / time of an AE was missing and could not be determined, it was considered a TEAE. Unless otherwise specified, all AEs are TEAEs.

[0165] The number and percentage of participants with AEs, AEs related to trial interventions, SAEs, and SAEs related to trial interventions are provided, as well as the number and percentage of participants by SOC and PT. AEs and AEs related to trial interventions also provide the number and percentage of participants by SOC, PT, and severity. AEs resulting in death will be tabulated.

[0166] Secondary End Point Analysis

[0167] Efficacy indicators

[0168] According to RECIST v1.1 criteria, the number and percentage of ORR and DCR assessed by investigators and BIRC were calculated in groups, and the 95% CI was calculated using the Clopper-Pearson exact method. If applicable, the Kaplan-Meier method was used to analyze PFS, DoR, and OS, and the median time and its 95% CI were estimated. The censoring rate and quartiles were listed separately, and the Kaplan-Meier curve was plotted.

[0169] Pharmacokinetic characteristics

[0170] Based on the PKCS, JMT101 and docetaxel concentrations were summarized for each group of subjects at each time point according to the planned blood collection time, including the mean, standard deviation, median, maximum, minimum, coefficient of variation, geometric mean, and geometric coefficient of variation. JMT101 and docetaxel concentrations for all subjects were tabulated.

[0171] Immunogenicity characteristics

[0172] Analyze based on the IS. Tabulate all antidrug antibody (ADA) results, titers, and neutralizing antibody (NAb) results. Summarize ADA incidence, time to first ADA-positive appearance, and duration. If applicable, conduct exploratory analyses of the impact of immunogenicity on drug PK (pharmacokinetics), safety, and efficacy.

[0173] Biomarker analysis

[0174] Analysis of the correlation between EGFR protein expression and amplification and efficacy and safety.

[0175] 2) Initial efficacy exploration stage (Stage II)

[0176] Analyze the dataset

[0177] ITT: Includes all randomized participants. Participants will be analyzed according to the randomly assigned treatment group. Participant demographics, baseline characteristics, and efficacy analyses will be based on the ITT population.

[0178] SS: Includes all successfully enrolled participants who received at least one trial intervention. SS is used for safety and tolerability analyses. In safety analyses, all participants will be analyzed based on the actual treatment group they received.

[0179] PKCS: Participants who have received at least one dose of JMT101 or docetaxel injection formulation A and have at least one evaluable PK concentration data after dosing.

[0180] IS: Participants who have received at least 1 prior JMT101 treatment and have baseline and at least one post-baseline immunogenicity data.

[0181] Demographic and baseline analyses

[0182] Same analysis content as Stage Ⅰ

[0183] Primary Endpoint Analysis

[0184] According to RECIST v1.1 criteria, the number and percentage of ORR assessed by BIRC were calculated in groups, and the 95% CI was calculated using the Clopper-Pearson exact method.

[0185] Secondary End Point Analysis

[0186] Efficacy indicators

[0187] According to RECIST v1.1 criteria, the number and percentage of DCR assessed by BIRC were calculated in groups, and the Clopper-Pearson exact method was used to calculate the 95% CI. The Kaplan-Meier method was used to analyze PFS and DoR, and the median time and its 95% CI were estimated. The censoring rate and quartiles were listed separately, and the Kaplan-Meier curve was drawn.

[0188] According to RECIST v1.1 criteria, the number and percentage of ORR and DCR assessed by the investigators were calculated in groups, and the Clopper-Pearson exact method was used to calculate the 95% CI. The Kaplan-Meier method was used to analyze PFS, DoR, and OS, and the median time and its 95% CI were estimated. The censoring rate, quartiles, and Kaplan-Meier curves were listed separately.

[0189] Security

[0190] All AEs were coded using MedDRA. Only TEAEs (TEAEs) occurring on or after the first dose of the trial intervention and no later than 30 days after the last dose were analyzed. Non-TEAEs were not included in the analysis and were simply tabulated. If the onset date / time of an AE was incomplete, it was determined to be a TEAE based on the available information. If the onset date / time of an AE was missing and could not be determined, it was considered a TEAE. Unless otherwise specified, all AEs are TEAEs.

[0191] The number and percentage of participants with AEs, AEs related to trial interventions, SAEs, and SAEs related to trial interventions are provided, as well as the number and percentage of participants by SOC and PT. AEs and AEs related to trial interventions also provide the number and percentage of participants by SOC, PT, and severity. AEs resulting in death will be tabulated.

[0192] Pharmacokinetic characteristics

[0193] Based on the PKCS, JMT101 concentrations, total docetaxel, and free docetaxel concentrations were summarized for each group of subjects at each time point according to the planned blood collection time, including the mean, standard deviation, median, maximum, minimum, coefficient of variation, geometric mean, and geometric coefficient of variation. JMT101, total docetaxel, and free docetaxel concentrations were tabulated for all subjects.

[0194] Immunogenicity characteristics

[0195] Analyze based on the IS. Tabulate all antidrug antibody (ADA) titers, and neutralizing antibody (NAb) results. Summarize ADA incidence, time to first ADA positivity, and duration. If applicable, conduct exploratory analyses of the impact of immunogenicity on drug PK, safety, and efficacy.

[0196] Biomarker analysis

[0197] Correlation analysis between EGFR protein expression and amplification and efficacy and safety

[0198] 3) Efficacy confirmation stage (Stage III)

[0199] Analyze the dataset

[0200] Same as the definition of the Stage II analysis data set.

[0201] Demographic and baseline analyses

[0202] Same analysis content as Stage Ⅰ

[0203] Primary Endpoint Analysis

[0204] OS was analyzed using the Kaplan-Meier method, including estimating the median time and its 95% CI, listing the censoring rate, quartiles, and drawing the Kaplan-Meier curve.

[0205] Secondary End Point Analysis

[0206] Efficacy indicators

[0207] According to RECIST v1.1 criteria, the number and percentage of ORR and DCR assessed by the investigator were calculated in groups, and the Clopper-Pearson exact method was used to calculate the 95% CI. The Kaplan-Meier method was used to analyze PFS and DoR, and the median time and its 95% CI were estimated. The censoring rate and quartiles were listed separately, and the Kaplan-Meier curve was drawn.

[0208] Security

[0209] All AEs were coded using MedDRA. Only TEAEs (TEAEs) occurring on or after the first dose of the trial intervention and no later than 30 days after the last dose were analyzed. Non-TEAEs were not included in the analysis and were simply tabulated. If the onset date / time of an AE was incomplete, it was determined to be a TEAE based on the available information. If the onset date / time of an AE was missing and could not be determined, it was considered a TEAE. Unless otherwise specified, all AEs are TEAEs.

[0210] The number and percentage of participants with AEs, AEs related to trial interventions, SAEs, and SAEs related to trial interventions are provided, as well as the number and percentage of participants by SOC and PT. AEs and AEs related to trial interventions also provide the number and percentage of participants by SOC, PT, and severity. AEs resulting in death will be tabulated.

[0211] Pharmacokinetic characteristics

[0212] Based on the PKCS, JMT101 concentrations, total docetaxel, and free docetaxel concentrations were summarized for each group of subjects at each time point according to the planned blood collection time, including the mean, standard deviation, median, maximum, minimum, coefficient of variation, geometric mean, and geometric coefficient of variation. JMT101 and docetaxel concentrations for all subjects were tabulated.

[0213] Immunogenicity characteristics

[0214] Analyze based on the IS. Tabulate all antidrug antibody (ADA) titers, and neutralizing antibody (NAb) results. Summarize ADA incidence, time to first ADA positivity, and duration. If applicable, conduct exploratory analyses of the impact of immunogenicity on drug PK, safety, and efficacy.

[0215] Biomarker analysis

[0216] Correlation between EGFR protein expression and amplification and efficacy and safety.

[0217] mid-term analysis

[0218] This study may conduct an interim analysis in Stage III, which is planned to be performed when approximately 194 OS events are observed in all participants (70% of the planned total number of events). The effective boundaries of the interim analysis and final analysis are determined using the O'Brien-Fleming α spending function method.

[0219] The iDMC will make recommendations based on the results of the interim analysis.

[0220] Test results

[0221] Efficacy:

[0222] As of February 6, 2025, a total of 100 subjects were enrolled in this trial, and 74 subjects had at least one efficacy evaluation, including:

[0223] - JMT101 combined with docetaxel injection formulation A: 26 patients, 6 patients achieved PR, and the ORR was 23% (6 / 26).

[0224] - JMT101 combined with docetaxel injection B: 25 patients, 4 patients achieved PR, and the ORR was 16% (4 / 25).

[0225] -Docetaxel injection A: 23 patients, 1 patient achieved PR, and the ORR was 4.3% (1 / 23).

[0226] Compared with the single-drug group (docetaxel injection formulation A), the combination group achieved significantly better results. mPFS and mOS have not yet been achieved.

[0227] Security:

[0228] There was no significant difference in the incidence of grade ≥3 AEs among the groups, and the overall safety was controllable.

[0229] The sequence information of the antibodies and their components involved in this application is shown in Table 1.

[0230] Table 1 Sequence information of antibodies and their components involved in this application

Claims

1. A combination drug for preventing or treating cancer, comprising an anti-EGFR antibody or fragment thereof (eg, antigen-binding fragment) and a taxane drug administered simultaneously or separately.

2. The combined drug according to claim 1, characterized in that The cancer is selected from lung cancer, gastric cancer, liver cancer, breast cancer, esophageal cancer, kidney cancer, bladder cancer, cervical cancer, colorectal cancer and lymphoma; preferably, the cancer is lung cancer; optionally, the lung cancer is selected from small cell carcinoma and non-small cell lung cancer, more preferably non-small cell carcinoma, further preferably non-small cell lung cancer after failure of previous first-line treatment, further preferably squamous cell non-small cell lung cancer after failure of previous first-line treatment, still further preferably driver gene-negative squamous cell non-small cell lung cancer after failure of previous first-line treatment, most preferably second-line or above squamous cell non-small cell lung cancer with negative driver genes and high EGFR expression.

3. The combined drug according to any one of claims 1 to 2, characterized in that The anti-EGFR antibody or fragment thereof comprises a heavy chain CDR1 as set forth in SEQ ID NO: 1 or SEQ ID NO: 2, a heavy chain CDR2 as set forth in SEQ ID NO: 3, and a heavy chain CDR3 as set forth in SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6, and / or a light chain CDR1 as set forth in SEQ ID NO: 7, a light chain CDR2 as set forth in SEQ ID NO: 8, and a light chain CDR3 as set forth in SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11; preferably, the anti-EGFR antibody or fragment thereof comprises a heavy chain CDR1 as set forth in SEQ ID NO: 1, a heavy chain CDR2 as set forth in SEQ ID NO: 3, and a heavy chain CDR3 as set forth in SEQ ID NO: 4, and / or a light chain CDR1 as set forth in SEQ ID NO: 7, a light chain CDR2 as set forth in SEQ ID NO: 8, and a light chain CDR3 as set forth in SEQ ID NO: 9; more preferably, the anti-EGFR antibody or fragment thereof comprises a heavy chain variable region as set forth in SEQ ID NO: 12, and / or a light chain CDR1 as set forth in SEQ ID NO:

13. NO:13; most preferably, the anti-EGFR antibody comprises the heavy chain shown in SEQ ID NO:14 and / or the light chain shown in SEQ ID NO:

15.

4. The combined drug according to any one of claims 1 to 3, characterized in that The anti-EGFR antibody or fragment thereof is selected from single-chain antibody (scFv), chimeric antibody, diabody, scFv-Fc bivalent molecule, dAb, Fab fragment, Fab' fragment, Fv or F(ab')2 fragment.

5. The combined drug according to any one of claims 1 to 3, characterized in that The anti-EGFR antibody is a full-length antibody; further, the anti-EGFR antibody includes a human IgG1 heavy chain constant region and / or a human light chain κ constant region.

6. The combined drug according to any one of claims 1 to 5, characterized in that The anti-EGFR antibody or fragment thereof is humanized.

7. The combined drug according to any one of claims 1 to 6, characterized in that The taxane drug is a taxane albumin nanoparticle drug or a taxane injection, such as a paclitaxel albumin nanoparticle drug or a paclitaxel injection, or a docetaxel albumin nanoparticle drug or a docetaxel injection, more preferably a docetaxel albumin nanoparticle drug or a docetaxel injection.

8. Use of an anti-EGFR antibody or a fragment thereof (such as an antigen-binding fragment) and a taxane drug in the preparation of a medicament for preventing or treating cancer.

9. The use according to claim 8, characterized in that The cancer is selected from lung cancer, gastric cancer, liver cancer, breast cancer, esophageal cancer, kidney cancer, bladder cancer, cervical cancer, colorectal cancer and lymphoma; preferably, the cancer is lung cancer; optionally, the lung cancer is selected from small cell carcinoma and non-small cell lung cancer, more preferably non-small cell carcinoma, further preferably non-small cell lung cancer after failure of previous first-line treatment, further preferably squamous cell non-small cell lung cancer after failure of previous first-line treatment, and even more preferably driver gene-negative squamous cell non-small cell lung cancer after failure of previous first-line treatment.

10. Use of an anti-EGFR antibody or fragment thereof (e.g., antigen-binding fragment) and a taxane in the preparation of a drug for preventing or treating second-line or higher-stage squamous cell non-small cell lung cancer that has failed previous first-line treatment, is driver gene-negative, and has high EGFR expression.

11. The use according to any one of claims 8 to 10, characterized in that The anti-EGFR antibody or fragment thereof comprises a heavy chain CDR1 as set forth in SEQ ID NO: 1 or SEQ ID NO: 2, a heavy chain CDR2 as set forth in SEQ ID NO: 3, and a heavy chain CDR3 as set forth in SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6, and / or a light chain CDR1 as set forth in SEQ ID NO: 7, a light chain CDR2 as set forth in SEQ ID NO: 8, and a light chain CDR3 as set forth in SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11; preferably, the anti-EGFR antibody or fragment thereof comprises a heavy chain CDR1 as set forth in SEQ ID NO: 1, a heavy chain CDR2 as set forth in SEQ ID NO: 3, and a heavy chain CDR3 as set forth in SEQ ID NO: 4, and / or a light chain CDR1 as set forth in SEQ ID NO: 7, a light chain CDR2 as set forth in SEQ ID NO: 8, and a light chain CDR3 as set forth in SEQ ID NO: 9; more preferably, the anti-EGFR antibody or fragment thereof comprises a heavy chain variable region as set forth in SEQ ID NO: 12, and / or a light chain CDR1 as set forth in SEQ ID NO:

13. NO:13; most preferably, the anti-EGFR antibody comprises the heavy chain shown in SEQ ID NO:14 and / or the light chain shown in SEQ ID NO:

15.

12. The use according to any one of claims 8 to 11, characterized in that The anti-EGFR antibody or fragment thereof is selected from single-chain antibody (scFv), chimeric antibody, diabody, scFv-Fc bivalent molecule, dAb, Fab fragment, Fab' fragment, Fv or F(ab')2 fragment.

13. The use according to any one of claims 8 to 11, characterized in that The anti-EGFR antibody is a full-length antibody; further, the anti-EGFR antibody includes a human IgG1 heavy chain constant region and / or a human light chain κ constant region.

14. The use according to any one of claims 8 to 13, characterized in that The anti-EGFR antibody or fragment thereof is humanized.

15. The use according to any one of claims 8 to 14, characterized in that The taxane drug is a taxane albumin nanoparticle drug or a taxane injection, such as a paclitaxel albumin nanoparticle drug or a paclitaxel injection, or a docetaxel albumin nanoparticle drug or a docetaxel injection, more preferably a docetaxel albumin nanoparticle drug or a docetaxel injection.

16. A method for preventing or treating cancer, comprising administering to an individual in need thereof an effective amount of an anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment) and a taxane drug.

17. The method according to claim 16, characterized in that The cancer is selected from lung cancer, gastric cancer, liver cancer, breast cancer, esophageal cancer, kidney cancer, bladder cancer, cervical cancer, colorectal cancer and lymphoma; preferably, the cancer is lung cancer; optionally, the lung cancer is selected from small cell carcinoma and non-small cell lung cancer, more preferably non-small cell carcinoma, further preferably non-small cell lung cancer after failure of previous first-line treatment, further preferably squamous cell non-small cell lung cancer after failure of previous first-line treatment, still further preferably driver gene-negative squamous cell non-small cell lung cancer after failure of previous first-line treatment, most preferably second-line or above squamous cell non-small cell lung cancer with negative driver genes and high EGFR expression.

18. The method according to any one of claims 16 to 17, characterized in that The anti-EGFR antibody or fragment thereof comprises a heavy chain CDR1 as set forth in SEQ ID NO: 1 or SEQ ID NO: 2, a heavy chain CDR2 as set forth in SEQ ID NO: 3, and a heavy chain CDR3 as set forth in SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6, and / or a light chain CDR1 as set forth in SEQ ID NO: 7, a light chain CDR2 as set forth in SEQ ID NO: 8, and a light chain CDR3 as set forth in SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11; preferably, the anti-EGFR antibody or fragment thereof comprises a heavy chain CDR1 as set forth in SEQ ID NO: 1, a heavy chain CDR2 as set forth in SEQ ID NO: 3, and a heavy chain CDR3 as set forth in SEQ ID NO: 4, and / or a light chain CDR1 as set forth in SEQ ID NO: 7, a light chain CDR2 as set forth in SEQ ID NO: 8, and a light chain CDR3 as set forth in SEQ ID NO: 9; more preferably, the anti-EGFR antibody or fragment thereof comprises a heavy chain variable region as set forth in SEQ ID NO: 12, and / or a light chain CDR1 as set forth in SEQ ID NO:

13. NO:13; most preferably, the anti-EGFR antibody comprises the heavy chain shown in SEQ ID NO:14 and / or the light chain shown in SEQ ID NO:

15.

19. The method according to any one of claims 16 to 18, characterized in that The anti-EGFR antibody or fragment thereof is selected from single-chain antibody (scFv), chimeric antibody, diabody, scFv-Fc bivalent molecule, dAb, Fab fragment, Fab' fragment, Fv or F(ab')2 fragment.

20. The method according to any one of claims 16 to 18, characterized in that The anti-EGFR antibody is a full-length antibody; further, the anti-EGFR antibody includes a human IgG1 heavy chain constant region and / or a human light chain κ constant region.

21. The method according to any one of claims 16 to 20, characterized in that The anti-EGFR antibody or fragment thereof is humanized.

22. The method according to any one of claims 16 to 21, characterized in that The taxane drug is a taxane albumin nanoparticle drug or a taxane injection, such as a paclitaxel albumin nanoparticle drug or a paclitaxel injection, or a docetaxel albumin nanoparticle drug or a docetaxel injection, more preferably a docetaxel albumin nanoparticle drug or a docetaxel injection.

23. The method according to any one of claims 20 to 22, characterized in that The anti-EGFR antibody or fragment thereof is administered before, simultaneously with, or after the taxane.

24. The method according to any one of claims 16 to 23, characterized in that The anti-EGFR antibody or fragment thereof is administered at a dose of 4 mg / kg to 10 mg / kg, preferably 4 mg / kg, 6 mg / kg, 8 mg / kg, 9 mg / kg or 10 mg / kg, more preferably 6 mg / kg or 9 mg / kg; and / or The anti-EGFR antibody or fragment thereof is administered once every 1-4 weeks, preferably once every 1 week, once every 2 weeks, once every 3 weeks or once every 4 weeks, more preferably once every 2 weeks or once every 3 weeks; and / or The dosage of the taxane drug is 50-150 mg / m 2 , preferably 50 mg / m 2 , 55mg / m 2 , 60mg / m 2 , 65mg / m 2 , 70mg / m 2 , 75mg / m 2 , 80mg / m 2 , 85mg / m 2 , 90mg / m 2 , 95mg / m 2 , 100mg / m 2 , 105mg / m 2 , 110mg / m 2 , 115mg / , 120mg / m 2 , 125mg / m 2 , 130mg / m 2 , 135mg / m 2 , 140mg / m 2 , 145mg / m 2 or 150 mg / m 2 More preferably, 60 mg / m 2 , 65mg / m 2 , 70mg / m 2 , 75mg / m 2 , 80mg / m 2 , 85mg / m 2 , 90mg / m 2 , 95mg / m 2 or 100 mg / m 2 More preferably, it is 60 mg / m 2 , 75mg / m 2 or 100 mg / m 2 and / or The taxanes are administered once every 1-4 weeks, preferably once every 1 week, once every 2 weeks, once every 3 weeks or once every 4 weeks, more preferably once every 2 weeks or once every 3 weeks.

25. The method according to any one of claims 16 to 24, characterized in that The method comprises first administering the anti-EGFR antibody or its fragment at a dosage of 6 mg / kg, and then administering the taxane drug at a dosage of 75 mg / m 2 After an interval of 2 weeks, the anti-EGFR antibody or its fragment was administered at a dose of 6 mg / kg, and then the taxane drug was administered at a dose of 75 mg / m 2 The administration regimen is cycled for 2 weeks, and the cycle is performed according to the above-mentioned dosing regimen until the disease progresses, the toxicity is intolerable, or the individual is evaluated as not benefiting from the treatment, whichever occurs first.

26. The method according to any one of claims 16 to 24, characterized in that The method comprises first administering the anti-EGFR antibody or its fragment at a dosage of 9 mg / kg, and then administering the taxane drug at a dosage of 100 mg / m 2 After an interval of 3 weeks, the anti-EGFR antibody or its fragment was administered again at a dose of 9 mg / kg, and then the taxane drug was administered at a dose of 100 mg / m 2 The administration regimen is cycled for 3 weeks, and the cycle is performed according to the above-mentioned dosing regimen until the disease progresses, the toxicity is intolerable, or the individual is evaluated as not benefiting from the treatment, whichever occurs first.

27. A combination of an anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment) and a taxane drug for use in preventing or treating cancer.

28. The combination for use according to claim 27, characterized in that The cancer is selected from lung cancer, gastric cancer, liver cancer, breast cancer, esophageal cancer, kidney cancer, bladder cancer, cervical cancer, colorectal cancer and lymphoma; preferably, the cancer is lung cancer; optionally, the lung cancer is selected from small cell carcinoma and non-small cell lung cancer, more preferably non-small cell carcinoma, further preferably non-small cell lung cancer after failure of previous first-line treatment, further preferably squamous cell non-small cell lung cancer after failure of previous first-line treatment, still further preferably driver gene-negative squamous cell non-small cell lung cancer after failure of previous first-line treatment, most preferably second-line or above squamous cell non-small cell lung cancer with negative driver genes and high EGFR expression.

29. The combination for use according to any one of claims 27-28, characterized in that The anti-EGFR antibody or fragment thereof comprises a heavy chain CDR1 as set forth in SEQ ID NO: 1 or SEQ ID NO: 2, a heavy chain CDR2 as set forth in SEQ ID NO: 3, and a heavy chain CDR3 as set forth in SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6, and / or a light chain CDR1 as set forth in SEQ ID NO: 7, a light chain CDR2 as set forth in SEQ ID NO: 8, and a light chain CDR3 as set forth in SEQ ID NO: 9, SEQ ID NO: 10, or SEQ ID NO: 11; preferably, the anti-EGFR antibody or fragment thereof comprises a heavy chain CDR1 as set forth in SEQ ID NO: 1, a heavy chain CDR2 as set forth in SEQ ID NO: 3, and a heavy chain CDR3 as set forth in SEQ ID NO: 4, and / or a light chain CDR1 as set forth in SEQ ID NO: 7, a light chain CDR2 as set forth in SEQ ID NO: 8, and a light chain CDR3 as set forth in SEQ ID NO: 9; more preferably, the anti-EGFR antibody or fragment thereof comprises a heavy chain variable region as set forth in SEQ ID NO: 12, and / or a light chain CDR1 as set forth in SEQ ID NO:

13. NO:13; most preferably, the anti-EGFR antibody comprises the heavy chain shown in SEQ ID NO:14 and / or the light chain shown in SEQ ID NO:

15.

30. The combination for use according to any one of claims 27 to 29, characterized in that The anti-EGFR antibody or fragment thereof is selected from single-chain antibody (scFv), chimeric antibody, diabody, scFv-Fc bivalent molecule, dAb, Fab fragment, Fab' fragment, Fv or F(ab')2 fragment.

31. The combination for use according to any one of claims 27 to 29, characterized in that The anti-EGFR antibody is a full-length antibody; further, the anti-EGFR antibody includes a human IgG1 heavy chain constant region and / or a human light chain κ constant region.

32. The combination for use according to any one of claims 27 to 31, characterized in that The anti-EGFR antibody or fragment thereof is humanized.

33. The combination for use according to any one of claims 27 to 32, characterized in that The taxane drug is a taxane albumin nanoparticle drug or a taxane injection, such as a paclitaxel albumin nanoparticle drug or a paclitaxel injection, or a docetaxel albumin nanoparticle drug or a docetaxel injection, more preferably a docetaxel albumin nanoparticle drug or a docetaxel injection.

34. The combination for use according to any one of claims 27 to 33, characterized in that The anti-EGFR antibody or fragment thereof is administered before, simultaneously with, or after the taxane.

35. The combination for use according to any one of claims 27 to 34, characterized in that The anti-EGFR antibody or fragment thereof is administered at a dose of 4 mg / kg to 10 mg / kg, preferably 4 mg / kg, 6 mg / kg, 8 mg / kg, 9 mg / kg or 10 mg / kg, more preferably 6 mg / kg or 9 mg / kg; and / or The anti-EGFR antibody or fragment thereof is administered once every 1-4 weeks, preferably once every 1 week, once every 2 weeks, once every 3 weeks or once every 4 weeks, more preferably once every 2 weeks or once every 3 weeks; and / or The dosage of the taxane drug is 50-150 mg / m 2 , preferably 50 mg / m 2 , 55mg / m 2 , 60mg / m 2 , 65mg / m 2 , 70mg / m 2 , 75mg / m 2 , 80mg / m 2 , 85mg / m 2 , 90mg / m 2 , 95mg / m 2 , 100mg / m 2 , 105mg / m 2 , 110mg / m 2 , 115mg / , 120mg / m 2 , 125mg / m 2 , 130mg / m 2 , 135mg / m 2 , 140mg / m 2 , 145mg / m 2 or 150 mg / m 2 More preferably, 60 mg / m 2 , 65mg / m 2 , 70mg / m 2 , 75mg / m 2 , 80mg / m 2 , 85mg / m 2 , 90mg / m 2 , 95mg / m 2 or 100 mg / m 2 More preferably, it is 60 mg / m 2 , 75mg / m 2 or 100 mg / m 2 and / or The taxanes are administered once every 1-4 weeks, preferably once every 1 week, once every 2 weeks, once every 3 weeks or once every 4 weeks, more preferably once every 2 weeks or once every 3 weeks.

36. The combination for use according to any one of claims 27 to 35, characterized in that The method comprises first administering the anti-EGFR antibody or its fragment at a dosage of 6 mg / kg, and then administering the taxane drug at a dosage of 75 mg / m 2 After an interval of 2 weeks, the anti-EGFR antibody or its fragment was administered at a dose of 6 mg / kg, and then the taxane drug was administered at a dose of 75 mg / m 2 The administration regimen is cycled for 2 weeks, and the cycle is performed according to the above-mentioned dosing regimen until the disease progresses, the toxicity is intolerable, or the individual is evaluated as not benefiting from the treatment, whichever occurs first.

37. The combination for use according to any one of claims 27 to 35, characterized in that The method comprises first administering the anti-EGFR antibody or its fragment at a dosage of 9 mg / kg, and then administering the taxane drug at a dosage of 100 mg / m 2 After an interval of 3 weeks, the anti-EGFR antibody or its fragment was administered again at a dose of 9 mg / kg, and then the taxane drug was administered at a dose of 100 mg / m 2 The administration regimen is cycled for 3 weeks, and the cycle is performed according to the above-mentioned dosing regimen until the disease progresses, the toxicity is intolerable, or the individual is evaluated as not benefiting from the treatment, whichever occurs first.

38. An anti-EGFR antibody or a fragment thereof (eg, an antigen-binding fragment), for use in preventing or treating cancer in combination with a taxane drug.

39. A taxane drug for use in preventing or treating cancer in combination with an anti-EGFR antibody or a fragment thereof (e.g., an antigen-binding fragment).