Pharmaceutical combinations containing TEAD inhibitors and their use for the treatment of cancer - Patents.com

Abstract

The present invention relates to a pharmaceutical combination comprising a TEAD inhibitor in combination with a first and, optionally, a second therapeutically active agent. The present invention also relates to a method of treating cancer comprising administering to a subject in need thereof a TEAD inhibitor in combination with a first and, optionally, a second therapeutically active agent.

Description

[Technical Field]

[0001] The present invention relates to pharmaceutical combinations comprising a TEAD inhibitor in combination with a first and, optionally, a second therapeutically active agent. The present invention also relates to methods of treating cancer comprising administering to a subject in need thereof a TEAD inhibitor in combination with a first and, optionally, a second therapeutically active agent. [Background technology]

[0002] The emergence of targeted cancer therapies has extended patient survival for a variety of malignancies and helped us understand tumor complexity through the study of drug resistance mechanisms. Clinical responses to targeted drugs are generally incomplete and / or transient, resulting from multiple factors that can be broadly categorized into two classes: toxicity, which prevents optimal drug administration and thus limits target engagement (Brana and Siu 2012; Chapman, Solit et al. 2014), and the cancer's ability to adapt and maintain proliferative capacity in response to perturbations (Druker 2008; Chandarlapaty 2012; Doebele, Pilling et al. 2012; Duncan, Whittle et al. 2012; Katayama, Shaw et al. 2012; Lito, Rosen et al. 2013; Sullivan and Flaherty 2013; Solit and Rosen 2014). Drug combinations can address both of these factors by improving overall efficacy and simultaneously targeting tumor robustness and complexity to combat resistance (Robert, Karaszewska et al. 2015, Turner, Ro et al. 2015). It remains to be determined how many drugs and which processes need to be targeted in combination to overcome a particular type of cancer. However, it is almost certain that various pathways or drivers will need to be inhibited, which will likely require more than one drug (Bozic, Reiter et al. 2013).

[0003] Despite the many treatment options for patients with certain types of cancer, there remains a need for effective and safe combination therapies that can be administered for the treatment of cancer. Summary of the Invention

[0004] It is an object of the present invention to provide agents for improving the treatment of cancer, particularly by inhibiting cell growth (proliferation) and / or inducing apoptosis (cell death). It is an object of the present invention to discover novel combination therapies that selectively synergize to inhibit proliferation and / or induce apoptosis.

[0005] Surprisingly, it has been found that a pharmaceutical combination comprising i) a TEAD inhibitor, ii) a first additional therapeutic active agent, and optionally iii) a second additional therapeutic active agent, wherein the first and second additional therapeutic active agents (if present) are independently selected from the group consisting of KRAS G12 / G13 inhibitors, SHP2 inhibitors, EGFR inhibitors, PI3K inhibitors, MEK inhibitors, ERK inhibitors, MDM2 inhibitors, Raf inhibitors, CDK4 / 6 inhibitors and cMET inhibitors, is capable of synergistically inhibiting cancer growth and / or inducing cancer apoptosis, as demonstrated in the examples.

[0006] Thus, according to a first aspect of the present invention, there is provided herein a method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a TEAD inhibitor in combination with a first additional therapeutic active agent, and optionally a second additional therapeutic active agent, wherein the first and second additional therapeutic active agents (if present) are independently selected from the group consisting of a KRAS G12 / G13 inhibitor, a SHP2 inhibitor, an EGFR inhibitor, a PI3K inhibitor, a MEK inhibitor, an ERK inhibitor, an MDM2 inhibitor, a Raf inhibitor, a CDK4 / 6 inhibitor, and a cMET inhibitor.

[0007] According to a second aspect of the present invention, there is provided herein a TEAD inhibitor for use in the treatment of cancer, wherein the treatment further comprises the administration of a first additional therapeutic active agent, and optionally a second additional therapeutic active agent, wherein the first additional therapeutic active agent and the second additional therapeutic active agent (if present) are independently selected from the group consisting of a KRAS G12 / G13 inhibitor, a SHP2 inhibitor, an EGFR inhibitor, a PI3K inhibitor, a MEK inhibitor, an ERK inhibitor, an MDM2 inhibitor, a Raf inhibitor, a CDK4 / 6 inhibitor and a cMET inhibitor.

[0008] According to a third aspect of the present invention, there is provided herein a pharmaceutical combination comprising i) a TEAD inhibitor, ii) a first further therapeutically active agent, and optionally iii) a second further therapeutically active agent, wherein the first further therapeutically active agent and the second further therapeutically active agent (if present) are independently selected from the group consisting of a KRAS G12 / G13 inhibitor, a SHP2 inhibitor, an EGFR inhibitor, a PI3K inhibitor, a MEK inhibitor, an ERK inhibitor, an MDM2 inhibitor, a Raf inhibitor, a CDK4 / 6 inhibitor and a cMET inhibitor.

[0009] According to a fourth aspect of the present invention, there is provided herein a cMET inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0010] According to a fifth aspect of the present invention, there is provided herein an SHP2 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0011] According to a sixth aspect of the present invention, there is provided herein a MEK inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0012] According to a seventh aspect of the present invention, there is provided herein an ERK inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0013] According to an eighth aspect of the present invention, there is provided herein a Raf inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0014] According to a ninth aspect of the present invention, there is provided herein an EGFR inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0015] According to a tenth aspect of the present invention, there is provided herein a PI3K inhibitor for use in the treatment of cancer, wherein the treatment further comprises the administration of a TEAD inhibitor.

[0016] According to an eleventh aspect of the present invention, there is provided herein an MDM2 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0017] According to a twelfth aspect of the present invention, there is provided herein a CDK4 / 6 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor. [Brief explanation of the drawings]

[0018] [Figure 1]Female nude mice bearing H2122 or 2094-HX subcutaneous xenograft lung tumors were treated with either compound A (4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide), compound C (1-{6-[(4M)-4-(5-chloro-6- Mice were treated orally (po) once daily (QD) with [(1-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl}prop-2-en-1-one], AMG510 (also known as sotorasib), or combinations as indicated in the legend, or vehicle control. Values ​​are mean ± SEM (standard error of mean); sample size n = 4-7 mice per group. Tumor volume is expressed as a percent change from the measurement on day 0 of treatment. Left panel, efficacy results from the H2122 xenograft model. Diamonds indicate results from the combination of Compound A (220 mg / kg qd) and Compound C (100 mg / kg qd). Right panel, efficacy results from the 2094-HX patient-derived xenograft (PDX) human lung model. Treatment was stopped on study day 44, and tumor regrowth was observed during the treatment break for single-agent treated animals compared to combination-treated animals. [Figure 2] Female nude mice bearing nine different colorectal cancer (CRC) subcutaneous PDX tumors were treated orally (po) with agents as indicated in the legend. A mouse clinical trial (MCT) format was used, with n=2 for no treatment and n=1 for each treatment. Left panel: Tumor growth reduction is shown using no doubling of the volume parameter, expressed as a percentage of the value for all mice. Right panel: Values ​​are mean ± SEM; the mean percent change in best tumor volume (TV) compared to baseline is shown. [Figure 3]Female nude mice bearing Lu99 lung or ACC-MESO1 mesothelioma subcutaneous xenograft tumors were treated orally (po) with Compound A or Compound B (2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide) once daily (QD), TNO155 twice daily, or combinations as indicated in the legend, or vehicle control. Values ​​are mean ± SEM; sample size n = 5-9 mice per group. Tumor volumes are shown in the upper graph. Percent body weight change compared to baseline is shown in the lower graph. [Figure 4] Female nude mice bearing Lu99 lung subcutaneous xenograft tumors were orally (po) treated with single agents or drug combinations as indicated in the legend. Treatments were administered once daily (QD) for Compound A or Compound B, once daily for Compound C, and twice daily for TNO155. Values ​​are mean ± SEM; sample size n = 6 mice per group. Tumor volume is shown in the graph on the left. Percent body weight change compared to baseline is shown in the graph on the right. [Figure 5] Female nude mice bearing Lu99 or 2094-HX lung subcutaneous xenograft tumors were treated orally (po) with single agents or drug combinations as indicated in the legend. Values ​​are mean ± SEM; sample size n = 4-6 mice per group. Tumor volume is shown in the graph on the left. Percent body weight change compared to baseline is shown in the graph on the right. [Figure 6]Female nude mice bearing subcutaneous xenograft tumors were treated orally (po) with single agents or drug combinations as indicated in the legend. A) Antitumor efficacy and tolerability evaluation in the NCI-H2052 mesothelioma subcutaneous xenograft model. Values ​​are mean ± SEM; sample size n = 6 mice per group. B) Antitumor efficacy and tolerability evaluation in the 2094-HX lung subcutaneous xenograft model. Values ​​are mean ± SEM; sample size n = 5-6 mice per group. C) MCT was performed using 23 PDAC PDX models, with n = 1-2 per model and treatment. Tumor growth reduction is shown using the no doubling of volume parameter, expressed as a percentage of the mouse population. [Figure 7] Female nude mice bearing HT-29 BRAF mutant V600E CRC subcutaneous xenograft tumors were orally (po) treated with single agents or drug combinations as indicated in the legend. Compound A was used in both the single-agent and triple-combination arms at 100 mg / kg once daily for the first 2 weeks of treatment and at 200 mg / kg for the last 2 weeks of treatment. Values ​​are mean ± SEM; sample size n = 5 mice per group. Tumor volume is shown in the left panel. Percent body weight change compared to baseline is shown in the right panel. [Figure 8] Female nude mice bearing 5238-HX (left panel: efficacy) or HT-29 (middle panel: efficacy, and right panel: tolerability) BRAF V600E CRC subcutaneous xenograft tumors were orally (po) treated with single agents or combinations of drugs as indicated in the legend (Dab: dabrafenib; Tram: trametinib). Values ​​are mean ± SEM; sample size n = 6–14 mice per group (5238-HX), n = 6 rats per group (HT-29). [Figure 9] Female FVB mice bearing 24284-MA syngeneic subcutaneous tumors were treated orally (po) with single agents or drug combinations as indicated in the legend. Values ​​are mean ± SEM; sample size n = 5–6 mice per group. [Figure 10] The Compound G YAP / TEAD inhibitor was combined with the EGFR inhibitor EGF816 in the lung cancer cell line PC9, which harbors an activating EGFR mutation. [Figure 11] In vitro viability of MCF7 breast cancer cell lines (PIK3CA mutant) was assessed using the CellTiterGlo assay after 6 days of treatment with the YAP / TEAD inhibitor Compound A or Compound B and the PI3K inhibitor NVP-QAU421 (or QAU421) ((S)-N1-(5-(2-(tert-butyl)pyrimidin-4-yl)-4-methylthiazol-2-yl)pyrrolidine-1,2-dicarboxamide). % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 12] In vitro viability of the KRAS G12C mutant cell line LU-99 was assessed using CellTiterGlo after 6 days of treatment with the YAP / TEAD inhibitor compound D (2-((2S,4S)-5-chloro-2-((((1r,4S)-4-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide) in combination with various combinations of MAPK pathway inhibitors (MEK inhibitor MEKINIST / trametinib / NVP-CFF272 (CFF272), BRAF / CRAF inhibitor NVP-LXH254 (LXH254), and ERK inhibitor NVP-LTT462 (LTT462)). % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 13]In vitro viability of the lung BRAF-mutant colorectal cell line SW-1417 was assessed using CellTiterGlo after 6 days of treatment with the YAP / TEAD inhibitor compound E (2-((2S,4S)-5-chloro-6-fluoro-2-((((1s,4R)-4-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide) in combination with various combinations of MAPK pathway inhibitors (BRAF inhibitor TAFINLAR / dabrafenib / NVP-LIQ288 / LIQ288, MEK inhibitor MEKINIST / trametinib / NVP-CFF272 / CFF272, BRAF / CRAF inhibitor NVP-LXH254 (LXH254), and ERK inhibitor LTT462 (NVP-LTT462)). % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 14] In vitro viability of the CDKN2A-deficient mesothelioma cell line MSTO-211H was assessed using CellTiterGlo after 3 days of treatment with the YAP / TEAD inhibitor Compound D in combination with the p53-HDM2 inhibitor NVP-HDM201 (HDM201). % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 15] In vitro viability of the mesothelioma cell line MSTO-211H was assessed using CellTiterGlo after 3 days of treatment with the YAP / TEAD inhibitor Compound D in combination with the CDK4 / 6 inhibitor NVP-LEE011 (LEE011 or ribociclib). % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 16]In vitro viability of the lung cancer cell line HCC44 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ443 and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 17] In vitro viability of the lung cancer cell line HCC44 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor sotorasib and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor sotorasib and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 18] In vitro viability of the lung cancer cell line HCC44 was assessed using CellTiterGlo after 7 days of treatment with (top left) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor adagrasib, (top right) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor adagrasib and the SHP2 inhibitor TNO155, and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor adagrasib and the SHP2 inhibitor RMC-4550. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 19] In vitro viability of the lung cancer cell line HCC44 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound A in combination with the SHP2 inhibitor TNO-155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 20]In vitro viability of the lung cancer cell line HCC44 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ443 and (bottom) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 21] In vitro viability of the lung cancer cell line HCC44 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor sotorasib and (bottom) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor sotorasib and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 22] In vitro viability of the lung cancer cell line HCC44 was assessed using CellTiterGlo after 7 days of treatment with (top left) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor adagrasib, (top right) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor adagrasib and the SHP2 inhibitor TNO155, and (bottom) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor adagrasib and the SHP2 inhibitor RMC-4550. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 23] In vitro viability of the lung cancer cell line HCC44 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound B in combination with the SHP2 inhibitor TNO-155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 24]In vitro viability of the lung cancer cell line HCC44 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ443 and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 25] In vitro viability of the lung cancer cell line HCC44 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor sotorasib and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor sotorasib and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 26] In vitro viability of the lung cancer cell line HCC44 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor adagrasib, and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor adagrasib and the SHP2 inhibitor RMC-4550. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 27] In vitro viability of the colon cancer cell line SW1463 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ443 and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 28]In vitro viability of the colon cancer cell line SW1463 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor sotorasib and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor sotorasib and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 29] In vitro viability of the colon cancer cell line SW1463 was assessed using CellTiterGlo after 7 days of treatment with (top left) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor adagrasib, (top right) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor adagrasib and the SHP2 inhibitor TNO155, and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor adagrasib and the SHP2 inhibitor RMC-4550. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 30] In vitro viability of the colon cancer cell line SW1463 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound A in combination with the SHP2 inhibitor TNO-155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 31] In vitro viability of the colon cancer cell line SW1463 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ443 and (bottom) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 32]In vitro viability of the colon cancer cell line SW1463 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor sotorasib and (bottom) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor sotorasib and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 33] In vitro viability of the colon cancer cell line SW1463 was assessed using CellTiterGlo after 7 days of treatment with (top left) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor adagrasib, (top right) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor adagrasib and the SHP2 inhibitor TNO155, and (bottom) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor adagrasib and the SHP2 inhibitor RMC-4550. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 34] In vitro viability of the colon cancer cell line SW1463 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound B in combination with the SHP2 inhibitor TNO-155 (top). % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 35] In vitro viability of the colon cancer cell line SW1463 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ443 and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 36]In vitro viability of the colon cancer cell line SW1463 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor sotorasib and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor sotorasib and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 37] In vitro viability of the colon cancer cell line SW1463 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor adagrasib, and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor adagrasib and the SHP2 inhibitor RMC-4550. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 38] In vitro viability of the lung cancer cell line NCI-H2122 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 39] In vitro viability of the lung cancer cell line NCI-H2122 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 40]In vitro viability of the lung cancer cell line NCI-H2122 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 41] In vitro viability of the lung cancer cell line NCI-H1373 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 42] In vitro viability of the lung cancer cell line NCI-H1373 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound A in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 43] In vitro viability of the lung cancer cell line NCI-H1373 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 44]In vitro viability of the lung cancer cell line NCI-H1373 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound B in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 45] In vitro viability of the lung cancer cell line NCI-H1373 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 46] In vitro viability of the lung cancer cell line NCI-H1373 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound H in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 47] In vitro viability of the lung cancer cell line HCC-1171 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 48] In vitro viability of the lung cancer cell line HCC-1171 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound A in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 49]In vitro viability of the lung cancer cell line HCC-1171 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 50] In vitro viability of the lung cancer cell line HCC-1171 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound B in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 51] In vitro viability of the lung cancer cell line HCC-1171 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 52] In vitro viability of the lung cancer cell line HCC-1171 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound H in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 53]In vitro viability of the lung cancer cell line NCI-H358 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 54] In vitro viability of the lung cancer cell line NCI-H358 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound A in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 55] In vitro viability of the lung cancer cell line NCI-H358 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 56] In vitro viability of the lung cancer cell line NCI-H358 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound B in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 57]In vitro viability of the lung cancer cell line NCI-H358 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 58] In vitro viability of the lung cancer cell line NCI-H358 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound H in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 59] In vitro viability of the lung cancer cell line LU65 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor sotorasib and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor sotorasib and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 60] In vitro viability of the lung cancer cell line LU65 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor adagrasib and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor adagrasib and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 61]In vitro viability of the lung cancer cell line LU65 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ443. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 62] In vitro viability of the lung cancer cell line LU65 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ443. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 63] In vitro viability of the lung cancer cell line LU65 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ443 and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 64] In vitro viability of the colon cancer cell line SW837 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 65] In vitro viability of the colon cancer cell line SW837 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound A in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 66]In vitro viability of the colon cancer cell line SW837 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 67] In vitro viability of the colon cancer cell line SW837 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound B in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 68] In vitro viability of the colon cancer cell line SW837 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 69] In vitro viability of the colon cancer cell line SW837 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound H in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduction in cell number / cell death. [Figure 70]In vitro viability of the colon cancer cell line LIM2099 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound A in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 71] In vitro viability of the colon cancer cell line LIM2099 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound A in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 72] In vitro viability of the colon cancer cell line LIM2099 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound B in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 73] In vitro viability of the colon cancer cell line LIM2099 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound B in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 74]In vitro viability of the colon cancer cell line LIM2099 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ-443 and (bottom) the YAP / TEAD inhibitor Compound H in combination with the KRAS G12C inhibitor JDQ-443 and the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 75] In vitro viability of the colon cancer cell line LIM2099 was assessed using CellTiterGlo after 7 days of treatment with the YAP / TEAD inhibitor Compound H in combination with the SHP2 inhibitor TNO155. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. [Figure 76] In vitro viability of the lung cancer cell line NCI-H1792 was assessed using CellTiterGlo after 7 days of treatment with (top) the YAP / TEAD inhibitor Compound A in combination with the CDK4 / 6 inhibitor NVP-LEE011 (LEE011 or ribociclib) and (bottom) the YAP / TEAD inhibitor Compound A in combination with the CDK4 / 6 inhibitor NVP-LEE011 (LEE011 or ribociclib) and the KRAS G12C inhibitor JDQ443. % growth inhibition: 0-99 = delayed growth, 100 = growth arrest / inhibition, 101-200 = reduced cell number / cell death. DETAILED DESCRIPTION OF THE INVENTION

[0019] As noted above, one object of the present invention is to discover novel combination therapies that selectively synergize in inhibiting proliferation and / or inducing apoptosis.

[0020] Accordingly, the present invention provides the following numbered embodiments:

[0021] Embodiment 1. A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a TEAD inhibitor in combination with a first additional therapeutic active agent, and optionally a second additional therapeutic active agent, wherein the first additional therapeutic active agent and the second additional therapeutic active agent (if present) are independently selected from the group consisting of a KRAS G12 / G13 inhibitor, a SHP2 inhibitor, an EGFR inhibitor, a PI3K inhibitor, a MEK inhibitor, an ERK inhibitor, an MDM2 inhibitor, a Raf inhibitor, a CDK4 / 6 inhibitor, and a cMET inhibitor.

[0022] Embodiment 2. A TEAD inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a first additional therapeutic active agent, and optionally a second additional therapeutic active agent, wherein the first additional therapeutic active agent and the second additional therapeutic active agent (if present) are independently selected from the group consisting of a KRAS G12 / G13 inhibitor, a SHP2 inhibitor, an EGFR inhibitor, a PI3K inhibitor, a MEK inhibitor, an ERK inhibitor, an MDM2 inhibitor, a Raf inhibitor, a CDK4 / 6 inhibitor and a cMET inhibitor.

[0023] Embodiment 3. A combination comprising i) a TEAD inhibitor, ii) a first additional therapeutically active agent, and optionally iii) a second additional therapeutically active agent, wherein the first additional therapeutically active agent and the second additional therapeutically active agent (if present) are independently selected from the group consisting of a KRAS G12 / G13 inhibitor, a SHP2 inhibitor, an EGFR inhibitor, a PI3K inhibitor, a MEK inhibitor, an ERK inhibitor, an MDM2 inhibitor, a Raf inhibitor, a CDK4 / 6 inhibitor and a cMET inhibitor.

[0024] Embodiment 4. The method of embodiment 1, the TEAD inhibitor for use according to embodiment 2, or the combination according to embodiment 3, wherein the first further therapeutically active agent is a KRAS G12 / G13 inhibitor (e.g., a KRAS G12C inhibitor), e.g., in the absence of a second therapeutically active agent.

[0025] Embodiment 5. The method according to embodiment 4, the TEAD inhibitor for use according to embodiment 4, or the combination according to embodiment 4, wherein the second additional therapeutically active agent is present and is a SHP2 inhibitor.

[0026] Embodiment 6. The method of embodiment 1, the TEAD inhibitor for use of embodiment 2, or the combination of embodiment 3, wherein the first additional therapeutically active agent is a SHP2 inhibitor, e.g., in the absence of a second therapeutically active agent.

[0027] Embodiment 7. The method of embodiment 1, the TEAD inhibitor for use according to embodiment 2, or the combination according to embodiment 3, wherein the first further therapeutically active agent is an EGFR inhibitor, e.g., in the absence of a second therapeutically active agent.

[0028] Embodiment 8. The method of embodiment 1, the TEAD inhibitor for use according to embodiment 2, or the combination according to embodiment 3, wherein the first further therapeutically active agent is a PI3K inhibitor, e.g., in the absence of a second therapeutically active agent.

[0029] Embodiment 9. The method of embodiment 1, the TEAD inhibitor for use according to embodiment 2, or the combination according to embodiment 3, wherein the first further therapeutically active agent is an MDM2 inhibitor, e.g., in the absence of a second therapeutically active agent.

[0030] Embodiment 10. The method of embodiment 1, the TEAD inhibitor for use according to embodiment 2, or the combination according to embodiment 3, wherein the first further therapeutically active agent is a CDK4 / 6 inhibitor, e.g., in the absence of a second therapeutically active agent.

[0031] Embodiment 10a. The method of embodiment 10, the TEAD inhibitor for use of embodiment 10, or the combination of embodiment 10, wherein the first additional therapeutically active agent is a CDK4 / 6 inhibitor (e.g., ribociclib or a pharmaceutically acceptable salt thereof) and the second therapeutically active agent is a KRAS G12C inhibitor (e.g., JDQ443 or a pharmaceutically acceptable salt thereof).

[0032] Embodiment 10b. The method according to embodiment 10a, the TEAD inhibitor for use according to embodiment 10a, or the combination according to embodiment 10a, wherein the TEAD inhibitor is compound A (4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide) or a pharmaceutically acceptable salt.

[0033] Embodiment 10c. The method according to embodiment 10a, the TEAD inhibitor for use according to embodiment 10a, or the combination according to embodiment 10a, wherein the TEAD inhibitor is compound B (2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide) or a pharmaceutically acceptable salt thereof.

[0034] Embodiment 11. The method of embodiment 1, the TEAD inhibitor for use of embodiment 2, or the combination of embodiment 3, wherein the first additional therapeutically active agent is a MEK inhibitor, e.g., in the absence of a second therapeutically active agent.

[0035] Embodiment 12. The method of embodiment 1, the TEAD inhibitor for use according to embodiment 2, or the combination according to embodiment 3, wherein the first further therapeutically active agent is an ERK inhibitor, e.g., in the absence of a second therapeutically active agent.

[0036] Embodiment 13. The method according to embodiment 11 or embodiment 12, the TEAD inhibitor for use according to embodiment 11 or embodiment 12, or the combination according to embodiment 11 or embodiment 12, wherein a second further therapeutically active agent is present, and the second further therapeutically active agent is a Raf inhibitor.

[0037] Embodiment 14. The method of embodiment 1, the TEAD inhibitor for use according to embodiment 2, or the combination according to embodiment 3, wherein the first further therapeutically active agent is a cMET inhibitor, e.g., in the absence of a second therapeutically active agent.

[0038] Embodiment 15. A cMET inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0039] Embodiment 16. A KRAS G12 / G13 inhibitor (e.g., a KRAS G12C inhibitor) for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0040] Embodiment 17. A KRAS G12 / G13 inhibitor for use according to embodiment 16, wherein the treatment further comprises administration of an SHP2 inhibitor.

[0041] Embodiment 18. An SHP2 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0042] Embodiment 19. The SHP2 inhibitor for use according to embodiment 18, wherein the treatment further comprises administration of a KRAS G12 / G13 inhibitor (e.g., a KRAS G12C inhibitor).

[0043] Embodiment 20. A MEK inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0044] Embodiment 21. An ERK inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0045] Embodiment 22. The MEK inhibitor for use according to embodiment 20 or the ERK inhibitor for use according to embodiment 21, wherein the treatment further comprises administration of a Raf inhibitor.

[0046] Embodiment 23. A Raf inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0047] Embodiment 24. The Raf inhibitor for use according to embodiment 23, wherein the treatment further comprises administration of a MEK inhibitor.

[0048] Embodiment 25. The Raf inhibitor for use according to embodiment 23, wherein the treatment further comprises administration of an ERK inhibitor.

[0049] Embodiment 26. An EGFR inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0050] Embodiment 27. A PI3K inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0051] Embodiment 28. An MDM2 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0052] Embodiment 29. A CDK4 / 6 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor.

[0053] Embodiment 30. The method according to any one of embodiments 1 and 4 to 14, the TEAD inhibitor for use according to any one of embodiments 2 and 4 to 14, the combination according to any one of claims 3 to 14, the cMET inhibitor for use according to embodiment 15, the KRAS G12 / G13 inhibitor for use according to embodiment 16 or embodiment 17, the SHP2 inhibitor for use according to embodiment 18 or embodiment 19, the MEK inhibitor for use according to embodiment 20 or embodiment 22, the ERK inhibitor for use according to embodiment 21 or embodiment 22, the Raf inhibitor for use according to any one of embodiments 23 to 25, the EGFR inhibitor for use according to embodiment 26, the PI3K inhibitor for use according to embodiment 27, the MDM2 inhibitor for use according to embodiment 28, or the CDK4 / 6 inhibitor for use according to embodiment 29, wherein the TEAD inhibitor is a YAP / TAZ-TEAD protein-protein interaction inhibitor.

[0054] Embodiment 31. The method according to embodiment 30, the TEAD inhibitor for use according to embodiment 30, the combination according to embodiment 30, the cMET inhibitor for use according to embodiment 30, and the KRAS inhibitor for use according to embodiment 30, wherein the TEAD inhibitor is a TEAD inhibitor of formula (I) or a pharmaceutically acceptable salt thereof, such as compound A (4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide) or a pharmaceutically acceptable salt thereof, or compound B (2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide) or a pharmaceutically acceptable salt thereof. A G12 / G13 inhibitor, a SHP2 inhibitor for use according to embodiment 30, a MEK inhibitor for use according to embodiment 30, an ERK inhibitor for use according to embodiment 30, a Raf inhibitor for use according to embodiment 30, an EGFR inhibitor for use according to embodiment 30, a PI3K inhibitor for use according to embodiment 30, an MDM2 inhibitor for use according to embodiment 30, or a CDK4 / 6 inhibitor for use according to embodiment 30.

[0055] Embodiment 31a. The method according to embodiment 31, the TEAD inhibitor for use according to embodiment 31, the combination according to embodiment 31, the cMET inhibitor for use according to embodiment 31, the KRAS G12 / G13 inhibitor for use according to embodiment 31, the SHP2 inhibitor for use according to embodiment 31, the MEK inhibitor for use according to embodiment 31, the ERK inhibitor for use according to embodiment 31, the Raf inhibitor for use according to embodiment 31, the EGFR inhibitor for use according to embodiment 31, the PI3K inhibitor for use according to embodiment 31, the MDM2 inhibitor for use according to embodiment 31, or the CDK4 / 6 inhibitor for use according to embodiment 31, wherein the TEAD inhibitor is compound A (4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide) or a pharmaceutically acceptable salt.

[0056] Embodiment 31b. The method according to embodiment 31, the TEAD inhibitor for use according to embodiment 31, the combination according to embodiment 31, the cMET inhibitor for use according to embodiment 31, the KRAS G12 / G13 inhibitor for use according to embodiment 31, the SHP2 inhibitor for use according to embodiment 31, the MEK inhibitor for use according to embodiment 31, the ERK inhibitor for use according to embodiment 31, the Raf inhibitor for use according to embodiment 31, the EGFR inhibitor for use according to embodiment 31, the PI3K inhibitor for use according to embodiment 31, the MDM2 inhibitor for use according to embodiment 31, or the CDK4 / 6 inhibitor for use according to embodiment 31, wherein the TEAD inhibitor is compound B (2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide) or a pharmaceutically acceptable salt.

[0057] Embodiment 31c. The TEAD inhibitor is: [ka] 31, or a pharmaceutically acceptable salt thereof.

[0058] Embodiment 32. The KRAS G12 / G13 inhibitor is selected from the group consisting of Compound C, sotorasib (Amgen), adagrasib (Mirati), D-1553 (InventisBio), BI1701963 (Boehringer), GDC6036 (Roche), JNJ74699157 (J&J), X-Chem KRAS (X-Chem), LY3537982 (Lilly), BI1823911 (Boehringer), AS KRAS G12C (Ascentage Pharma), SF KRAS G12C (Sanofi), RMC032 (Revolution Medicine), JAB-21822 (Jacobio Pharmaceuticals), AST-KRAS G12C (Allist Pharmaceuticals), AZ KRAS G12C (Astra Zeneca), NYU-12VC1 (New York the method according to any one of embodiments 1, 4, 5, 30 and 31, the TEAD inhibitor for use according to any one of embodiments 2, 4, 5, 30 and 31, the combination according to any one of embodiments 3 to 5, 30 and 31, the KRAS G12 / G13 inhibitor for use according to any one of embodiments 16, 17, 30 and 31, or the SHP2 inhibitor for use according to any one of embodiments 19, 30 and 31, wherein the KRAS G12C inhibitor is selected from: CI2491 (University), and RMC6291 (Revolution Medicines), or a pharmaceutically acceptable salt thereof.

[0059] Embodiment 32a. The method according to embodiment 32, the TEAD inhibitor for use according to embodiment 32, the combination according to embodiment 32, the KRAS G12 / G13 inhibitor for use according to embodiment 32, or the SHP2 inhibitor for use according to embodiment 32, wherein the KRAS G12 / G13 inhibitor is a KRAS G12C inhibitor selected from Compound C, sotorasib (Amgen) (also known as AMG510) and adagrasib (Mirati), or a pharmaceutically acceptable salt thereof.

[0060] Embodiment 33. The method according to embodiment 32, the TEAD inhibitor for use according to embodiment 32, the combination according to embodiment 32, the KRAS G12 / G13 inhibitor for use according to embodiment 32, or the SHP2 inhibitor for use according to embodiment 32, wherein the KRAS G12 / G13 inhibitor is KRAS G12C inhibitor compound C (1-{6-[(4M)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl}prop-2-en-1-one) or sotorasib (AMG510), or a pharmaceutically acceptable salt thereof.

[0061] Embodiment 34. The method according to embodiment 33, the TEAD inhibitor for use according to embodiment 33, the combination according to embodiment 33, the KRAS G12 / G13 inhibitor for use according to embodiment 33, or the SHP2 inhibitor for use according to embodiment 33, wherein the KRAS G12 / G13 inhibitor is the KRAS G12C inhibitor compound C, or a pharmaceutically acceptable salt thereof.

[0062] Embodiment 34a. The method according to embodiment 33, the TEAD inhibitor for use according to embodiment 33, the combination according to embodiment 33, the KRAS G12 / G13 inhibitor for use according to embodiment 33, or the SHP2 inhibitor for use according to embodiment 33, wherein the KRAS G12 / G13 inhibitor is sotorasib (AMG510), or a pharmaceutically acceptable salt thereof.

[0063] Embodiment 34b. The method according to embodiment 32, the TEAD inhibitor for use according to embodiment 32, the combination according to embodiment 32, the KRAS G12 / G13 inhibitor for use according to embodiment 32, or the SHP2 inhibitor for use according to embodiment 32, wherein the KRAS G12 / G13 inhibitor is adagrasib, or a pharmaceutically acceptable salt thereof.

[0064] Embodiment 35. The SHP2 inhibitor is TNO155 (Novartis), JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398(Navire), BR790(Shanghai Blueray), SH3809(Nanjing Sanhome), PF0724982(Pfizer), ERAS601(Erasca), RX-SHP2(Redx Pharma), ICP189(InnoCare), HBI2376(HUYA Bioscience), ETS001(Shanghai ETERN) Biopharma), TAS-ASTX (Taiho & Otsuka) The method according to any one of embodiments 1, 5, 6, and 30-34, the TEAD inhibitor for use according to any one of embodiments 2, 5, 6, and 30-34, the combination according to any one of embodiments 3, 5, 6, and 30-34, the KRAS G12 / G13 inhibitor for use according to any one of embodiments 17, and 30-34, or the SHP2 inhibitor for use according to any one of embodiments 18, 19, and 30-34, selected from the group consisting of X-37-SHP2 (X-37), or a pharmaceutically acceptable salt thereof.

[0065] Embodiment 35a. The method according to embodiment 35, the TEAD inhibitor for use according to embodiment 35, the combination for use according to embodiment 35, the KRAS G12 / G13 inhibitor for use according to embodiment 35 or the SHP2 inhibitor for use according to embodiment 35, wherein the SHP2 inhibitor is selected from the group consisting of TNO155, RMC4550 and RMC4630, or a pharmaceutically acceptable salt thereof.

[0066] Embodiment 36. The method according to embodiment 35, the TEAD inhibitor for use according to embodiment 35, the combination for use according to embodiment 35, the KRAS G12 / G13 inhibitor for use according to embodiment 35 or the SHP2 inhibitor for use according to embodiment 35, wherein the SHP2 inhibitor is TNO155, or a pharmaceutically acceptable salt thereof.

[0067] Embodiment 36a. The method according to embodiment 35, the TEAD inhibitor for use according to embodiment 35, the combination for use according to embodiment 35, the KRAS G12 / G13 inhibitor for use according to embodiment 35 or the SHP2 inhibitor for use according to embodiment 35, wherein the SHP2 inhibitor is RMC4550 or RMC4630, or a pharmaceutically acceptable salt thereof.

[0068] Embodiment 37. The cMET inhibitor is selected from the group consisting of crizotinib, capmatinib, tepotinib, AMG337, cabozantinib, savolitinib (AZD6094, HMPL-504), tivantinib, foretinib, voritinib, SU11274, PHA 665752, SGX523, BAY-853474, KRC-408, T-1840383, MK-2461, BMS-777607, JNJ-38877605, tivantinib (ARQ 197), PF-04217903, MGCD265, BMS-754807, BMS-794833, AMG-458, NVP-BVU972, AMG-208, golvatinib, norcantharidin, S49076, SAR125844, merestinib (LY2801653), onartuzumab, emibetuzumab, SAIT301, ABT-700, DN30, LY3164530, rilotumumab , ficlatuzumab, TAK701, and YYB-101, or a pharmaceutically acceptable salt thereof, for the method according to any one of embodiments 1, 14, 30, and 31, the TEAD inhibitor for use according to any one of embodiments 2, 4, 30, and 31, the combination according to any one of embodiments 3, 4, 30, and 31, or the cMET inhibitor for use according to embodiment 15.

[0069] Embodiment 38. The method according to embodiment 37, the TEAD inhibitor for use according to embodiment 37, the combination according to embodiment 37 or the cMET inhibitor for use according to embodiment 37, wherein the cMET inhibitor is i) tepotinib, or ii) capmatinib, or a pharmaceutically acceptable salt thereof.

[0070] Embodiment 39. The method according to any one of embodiments 1, 14, 30 and 31, the TEAD inhibitor for use according to any one of embodiments 2, 4, 30 and 31, the combination according to any one of embodiments 3, 4, 30 and 31 or the EGFR inhibitor for use according to embodiment 26, wherein the EGFR inhibitor is selected from the group consisting of cetuximab, panitumumab, erlotinib, gefitinib, osimertinib and nazartinib, or a pharmaceutically acceptable salt thereof.

[0071] Embodiment 40. The method according to embodiment 39, the TEAD inhibitor for use according to embodiment 39, the combination according to embodiment 39 or the EGFR inhibitor for use according to embodiment 39, wherein the EGFR inhibitor is nazartinib (also known as EGF816), or a pharmaceutically acceptable salt thereof.

[0072] Embodiment 41. The method according to any one of embodiments 1, 14, 30 and 31, the TEAD inhibitor for use according to any one of embodiments 2, 4, 30 and 31, the combination according to any one of embodiments 3, 4, 30 and 31 or the PI3K inhibitor for use according to embodiment 27, wherein the PI3K inhibitor is selected from the group consisting of AMG511, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib, QAU421 and umbralisib, or a pharmaceutically acceptable salt thereof.

[0073] Embodiment 42. The method according to any one of embodiments 1, 14, 30 and 31, the TEAD inhibitor for use according to any one of embodiments 2, 4, 30 and 31, the combination according to any one of embodiments 3, 4, 30 and 31 or the MDM2 inhibitor for use according to embodiment 28, wherein the MDM2 inhibitor is selected from the group consisting of nutlin-3a, idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademetan and HDM201 (also known as silymarin), or a pharmaceutically acceptable salt thereof.

[0074] Embodiment 43. The method according to embodiment 42, the TEAD inhibitor for use according to embodiment 42, the combination according to embodiment 42, or the MDM2 inhibitor for use according to embodiment 42, wherein the MDM2 inhibitor is HDM201, or a pharmaceutically acceptable salt thereof.

[0075] Embodiment 44. The method according to any one of embodiments 1, 14, 30 and 31, the TEAD inhibitor for use according to any one of embodiments 2, 4, 30 and 31, the combination according to any one of embodiments 3, 4, 30 and 31 or the CDK4 / 6 inhibitor for use according to embodiment 29, wherein the CDK4 / 6 inhibitor is selected from the group consisting of ribociclib, palbocyclib and abemaciclib, or a pharmaceutically acceptable salt thereof.

[0076] Embodiment 45. The method according to embodiment 44, the TEAD inhibitor for use according to embodiment 44, the combination according to embodiment 44, or the CDK4 / 6 inhibitor for use according to embodiment 44, wherein the CDK4 / 6 inhibitor is ribociclib, or a pharmaceutically acceptable salt thereof.

[0077] Embodiment 46. The method according to any one of embodiments 1, 14, 30 and 31, the TEAD inhibitor for use according to any one of embodiments 2, 4, 30 and 31, the combination according to any one of embodiments 3, 4, 30 and 31 or the MEK inhibitor for use according to embodiment 20 or embodiment 22 or the Raf inhibitor for use according to embodiment 24, wherein the MEK inhibitor is selected from the group consisting of pimasertib, PD-0325901, selumetinib, trametinib, binimetinib and cobimetinib, or a pharmaceutically acceptable salt thereof.

[0078] Embodiment 47. The method according to embodiment 46, the TEAD inhibitor for use according to embodiment 46, the combination according to embodiment 46, the MEK inhibitor for use according to 46, or the Raf inhibitor for use according to embodiment 46, wherein the MEK inhibitor is trametinib, or a pharmaceutically acceptable salt thereof.

[0079] Embodiment 48. The method according to any one of embodiments 1, 14, 30 and 31, the TEAD inhibitor for use according to any one of embodiments 2, 4, 30 and 31, the combination according to any one of embodiments 3, 4, 30 and 31 or the ERK inhibitor for use according to embodiment 21 or embodiment 22, or the Raf inhibitor for use according to embodiment 25, wherein the ERK inhibitor is selected from the group consisting of ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 and BVD-523, or a pharmaceutically acceptable salt thereof.

[0080] Embodiment 49. The method according to embodiment 48, the TEAD inhibitor for use according to embodiment 48, the combination according to embodiment 48, the ERK inhibitor for use according to 48, or the Raf inhibitor for use according to embodiment 48, wherein the ERK inhibitor is LTT462 (linetarquib) or ulixertinib, or a pharmaceutically acceptable salt thereof.

[0081] Embodiment 50. The method according to any one of embodiments 1, 14, 30, 31 and 46 to 49, the TEAD inhibitor for use according to any one of embodiments 2, 4, 30, 31 and 46 to 49, the combination according to any one of embodiments 3, 4, 30, 31 and 46 to 49, the MEK inhibitor for use according to embodiment 22, the ERK inhibitor for use according to embodiment 22 or the Raf inhibitor for use according to any one of embodiments 23 to 25, wherein the Raf inhibitor is selected from the group consisting of berbalafenib, naporafenib (also known as LXH254), encorafenib, vemurafenib and dabrafenib, or a pharmaceutically acceptable salt thereof.

[0082] Embodiment 51. The method according to embodiment 50, the TEAD inhibitor for use according to embodiment 50, the combination according to embodiment 50, the MEK inhibitor for use according to embodiment 50, the ERK inhibitor for use according to embodiment 50 or the Raf inhibitor for use according to embodiment 50, wherein the Raf inhibitor is dabrafenib or LXH254 (napolafenib), or a pharmaceutically acceptable salt thereof.

[0083] Embodiment 52. The method according to any one of embodiments 1, 4 to 14 and 30 to 51, the TEAD inhibitor for use according to any one of embodiments 2, 4 to 14 and 30 to 51, the cMET inhibitor for use according to any one of embodiments 15, 30, 31, 37 and 38, and the KRAS inhibitor for use according to any one of embodiments 16, 17 and 30 to 36, wherein the cancer is a TEAD-dependent cancer. a G12 / G13 inhibitor, a SHP2 inhibitor for use according to any one of embodiments 18, 19 and 30 to 36, a MEK inhibitor for use according to any one of embodiments 20, 22, 30, 31, 46, 47, 50 and 51, an ERK inhibitor for use according to any one of embodiments 21, 22, 30, 31 and 48 to 51, a Raf inhibitor for use according to any one of embodiments 23 to 25, 30, 31 and 46 to 51, an EGFR inhibitor for use according to any one of embodiments 26, 30, 31, 39 and 40, a PI3K inhibitor for use according to any one of embodiments 27, 30, 31 and 41, an MDM2 inhibitor for use according to any one of embodiments 28, 30, 31, 42 and 43, or a CDK4 / 6 inhibitor for use according to any one of embodiments 29 to 31, 44 and 45.

[0084] Embodiment 53. The method according to any one of embodiments 1, 4 to 14, and 30 to 52, the TEAD inhibitor for use according to any one of embodiments 2, 4 to 14, and 30 to 52, the cMET inhibitor for use according to any one of embodiments 15, 30, 31, 37, 38, and 52, and the KRAS inhibitor for use according to any one of embodiments 16, 17, 30 to 36, and 52, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, ovarian cancer, kidney cancer, uterine cancer, colorectal cancer, malignant pleural mesothelioma, pancreatic cancer, prostate cancer, gastric cancer, gastrointestinal stromal tumor, esophageal cancer, liver cancer, medulloblastoma, head and neck cancer, sarcoma, squamous cell carcinoma, epithelioid hemangioendothelioma, ependymal tumor, and osteosarcoma, for example, the cancer is malignant pleural mesothelioma. a G12 / G13 inhibitor, a SHP2 inhibitor for use according to any one of embodiments 18, 19, 30 to 36, and 52; a MEK inhibitor for use according to any one of embodiments 20, 22, 30, 31, 46, 47, and 50 to 52; an ERK inhibitor for use according to any one of embodiments 21, 22, 30, 31, and 48 to 52; a Raf inhibitor for use according to any one of embodiments 23 to 25, 30, 31, and 46 to 52; an EGFR inhibitor for use according to any one of embodiments 26, 30, 31, 39, 40, and 52; a PI3K inhibitor for use according to any one of embodiments 27, 30, 31, 41, and 52; an MDM2 inhibitor for use according to any one of embodiments 28, 30, 31, 42, 43, and 52; or a CDK4 / 6 inhibitor for use according to any one of embodiments 29 to 31, 44, 45, and 52.

[0085] Embodiment 53a. The method according to embodiment 53, wherein the cancer is colorectal cancer or lung cancer, the TEAD inhibitor for use according to embodiment 53, the cMET inhibitor for use according to embodiment 53, the KRAS G12 / G13 inhibitor for use according to embodiment 53, the SHP2 inhibitor for use according to embodiment 53, the MEK inhibitor for use according to embodiment 53, the ERK inhibitor for use according to embodiment 53, the Raf inhibitor for use according to embodiment 53, the EGFR inhibitor for use according to embodiment 53, the PI3K inhibitor for use according to embodiment 53, the MDM2 inhibitor for use according to embodiment 53, or the CDK4 / 6 inhibitor for use according to embodiment 53.

[0086] Embodiment 53b. The method according to any one of embodiments 1, 4 to 14 and 30 to 53a, the use of a TEAD inhibitor according to any one of embodiments 2, 4 to 14 and 30 to 53a, the use of a cMET inhibitor according to any one of embodiments 15, 30, 31, 37, 38 and 53a, the use of a KRAS G12 / G13 inhibitor according to any one of embodiments 16, 17, 30 to 36 and 53a, the use of an SHP2 inhibitor according to any one of embodiments 18, 19, 30 to 36 and 53a, the use of an MEK inhibitor according to any one of embodiments 20, 22, 30, 31, 46, 47 and 50 to 53a, the use of an ERK inhibitor according to any one of embodiments 21, 22, 30, 31 and 48 to 53a, the use of an ERK inhibitor according to any one of embodiments 23 to 25, 30, 31 and 46 to 53a. a Raf inhibitor for use according to any one of embodiments 26, 30, 31, 39, 40 and 53a; an EGFR inhibitor for use according to any one of embodiments 27, 30, 31, 41 and 53a; a PI3K inhibitor for use according to any one of embodiments 27, 30, 31, 41 and 53a; an MDM2 inhibitor for use according to any one of embodiments 28, 30, 31, 42, 43 and 53a; or a CDK4 / 6 inhibitor for use according to any one of embodiments 29 to 31, 44, 45 and 53a.

[0087] Embodiment 54. The method according to any one of embodiments 1, 4 to 14 and 30 to 53, the TEAD inhibitor for use according to any one of embodiments 2, 4 to 14 and 30 to 53, the cMET inhibitor for use according to any one of embodiments 15, 30, 31, 37, 38, 52 and 53, the KRAS inhibitor for use according to any one of embodiments 16, 17, 30 to 36, 52 and 53, wherein the TEAD inhibitor is administered on each of the first three days of a seven-day treatment cycle, and the treatment consists of at least two treatment cycles. G12 / G13 inhibitors, SHP2 inhibitors for use according to any one of embodiments 18, 19, 30 to 36, 52 and 53, MEK inhibitors for use according to any one of embodiments 20, 22, 30, 31, 46, 47 and 50 to 53, ERK inhibitors for use according to any one of embodiments 21, 22, 30, 31 and 48 to 53, Raf inhibitors for use according to any one of embodiments 23 to 25, 30, 31 and 46 to 53 an EGFR inhibitor for use according to any one of embodiments 26, 30, 31, 39, 40, 52 and 53; a PI3K inhibitor for use according to any one of embodiments 27, 30, 31, 41, 52 and 53; an MDM2 inhibitor for use according to any one of embodiments 28, 30, 31, 42, 43, 52 and 53; or a CDK4 / 6 inhibitor for use according to any one of embodiments 29 to 31, 44, 45, 52 and 53.

[0088] Embodiment 55. The method according to embodiment 54, the TEAD inhibitor according to embodiment 54, the cMET inhibitor according to embodiment 54, the KRAS G12 / G13 inhibitor for use according to embodiment 54, the SHP2 inhibitor for use according to embodiment 54, the MEK inhibitor for use according to embodiment 54, the ERK inhibitor for use according to embodiment 54, the Raf inhibitor for use according to embodiment 54, the EGFR inhibitor for use according to embodiment 54, the PI3K inhibitor for use according to embodiment 54, the MDM2 inhibitor for use according to embodiment 54, or the CDK4 / 6 inhibitor for use according to embodiment 54, wherein the daily dose of the TEAD inhibitor on each day of administration is 15 mg to 100 mg.

[0089] Embodiment 56. The method according to embodiment 55, the TEAD inhibitor according to embodiment 55, the cMET inhibitor according to embodiment 55, the KRAS G12 / G13 inhibitor for use according to embodiment 55, the SHP2 inhibitor for use according to embodiment 54, the MEK inhibitor for use according to embodiment 55, the ERK inhibitor for use according to embodiment 55, the Raf inhibitor for use according to embodiment 55, the EGFR inhibitor for use according to embodiment 55, the PI3K inhibitor for use according to embodiment 55, the MDM2 inhibitor for use according to embodiment 55, or the CDK4 / 6 inhibitor for use according to embodiment 55, wherein the daily dose of the TEAD inhibitor on each day of administration is 15, 30, 45, 60, 75 mg, 90 mg, or 100 mg.

[0090] It has been found that the combinations of the present invention can be used to effectively treat cancer, for example due to synergistic effects in inhibiting cell proliferation and / or inducing apoptosis.

[0091] In one embodiment of any one of the aspects of the invention, the TEAD inhibitor is a YAP / TAZ-TEAD protein-protein interaction inhibitor.

[0092] In one embodiment of any one of the aspects of the invention, the TEAD inhibitor is a TEAD inhibitor of formula (I), or a pharmaceutically acceptable salt thereof, such as compound A (4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide) or a pharmaceutically acceptable salt thereof, or compound B (2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide) or a pharmaceutically acceptable salt thereof; [ka] During the ceremony, W is O; and CH-R w Selected from; X is selected from CH; and N; Y is selected from CH; and N; Z is selected from CH; O; and NH; where Y is N and W is CH-R w and Z is O; A is, (i) phenyl (phenyl optionally substituted with halo; or haloC1-C3 alkoxy); (ii) a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S (the aromatic heterocyclic ring is optionally substituted with hydroxy; C1-C3 alkoxy; or oxo); and (iii) a halobenzodioxole moiety of the formula: [ka] Selected from; R w is selected from (i) hydrogen; (ii) hydroxy; (iii) C1-C3 alkoxy; (iv) hydroxy-C1-C3 alkyl; (v) C1-C3 alkyl; and (vi) C1-C3 alkoxy-C1-C3 alkyl; Q is (i)-C(R 7 )2-N(R 8 )-R1; (ii) a 9- or 10-membered partially saturated heteroaryl containing at least one N heteroatom; and (iii) a 4-, 5-, or 6-membered saturated heterocyclic ring containing at least one heteroatom or group of heteroatoms selected from N, O, S, -S(=O) and -S(=O)2, provided that at least one N heteroatom is present, and wherein the heterocyclic ring is unsubstituted or substituted with one or more substituents independently selected from hydroxy, C1-C3 alkyl, C1-C3 alkoxy, halo, and C1-C3 alkylene that form a bridge between two ring atoms of the saturated heterocyclic ring, thereby forming a bridged bicyclic structure; R1 is (i) hydrogen; (ii) optionally deuterated C1-C6 alkyl; and (iii) (CH2) 0~2 R 1a Selected from; R 1a (i) hydroxy C1-C4 alkyl; (ii) C1-C3 alkoxy; (iii) a 5- or 6-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O (the saturated heterocyclic ring is independently C1-C3 alkyl; (CH2) 0~1 C(O)di(C1-C3 alkyl)amino; SO2C1-C3 alkyl; C(O)C1-C3 alkyl; or optionally substituted one or more times with oxo; (iv) independently hydroxy; hydroxyC1-C4 alkyl; C1-C6 alkoxy; C(O)OC1-C3 alkyl; CO2H; SO2C1-C3 alkyl; haloC1-C3 alkyl; NHR 1b ;(CH2) 0~1 C(O)NR 1c R 1d C1-C6 alkyl; haloC1-C3 alkoxy-C1-C3 alkyl; halo; a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S; or two R 1e C-C cycloalkyl optionally substituted one or more times with a group; where two R bonded to the same carbon atom 1e together with the carbon atom to which they are attached form a 5-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O, or a C3-C6 cycloalkyl, wherein the saturated heterocyclic ring or cycloalkyl is optionally substituted with hydroxy or oxo; R 1b is selected from (i) C(O)C1-C3 alkyl; and (ii) SO2C1-C3 alkyl; R 1c and R 1d are each independently selected from: (i) hydrogen; (ii) C1-C3 alkyl; and (iii) hydroxy C1-C4 alkyl; R2 is selected from (i) hydrogen; and (ii) halo; R3 is selected from (i) halo; (ii) haloC1-C3 alkyl; and (iii) cyano; R4 is selected from (i) hydrogen; (ii) halo; and (iii) C1-C3 alkyl; R5 is (i) hydrogen; (ii) C3-C6 cycloalkyl; CO2H; SO2C1-C3 alkyl; a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S; or a 5- or 6-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O, the ring optionally substituted with C(O)C1-C3 alkyl; (iii) halo; (iv) hydroxy C1-C6 alkoxy (wherein alkoxy is optionally deuterated); (v) halo C1-C6 alkoxy optionally substituted with hydroxy; (vi) S-halo C1-C3 alkyl optionally substituted with hydroxy; (vii) C1-C3 alkoxy C1-C3 alkoxy; (viii) NR 5a R 5b (ix) C1-C3 alkyl; (x) a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S; and (xi) hydroxy; R 5a and R 5b are each independently selected from: (i) hydrogen; and (ii) C1-C3 alkyl; or R 5a and R 5b together with the nitrogen atom to which they are attached form a 5- or 6-membered saturated heterocyclic ring (the saturated heterocyclic ring optionally further bearing a hydroxy group); R6 is (i) hydrogen; (ii) cyano; (iii) C(O)NHR 6a ;(iv)NHR 6b and (v) C1-C3 alkoxy substituted with NH2 or hydroxy; R 6ais selected from (i) hydrogen; (ii) C1-C3 alkyl; (iii) C3-C6 cycloalkyl; (iv) a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S, wherein the aromatic heterocyclic ring is optionally substituted with C1-C3 alkyl; R 6b is C1-C3 alkyl substituted with NH2 or hydroxy; R 7 are each independently selected from hydrogen and C1-C3 alkyl; R 8 is hydrogen or C1-C3-alkyl.

[0093] In one embodiment of any one of the aspects of the invention, when a KRAS G12 / G13 inhibitor is present, the KRAS G12 / G13 inhibitor is a KRAS G12C inhibitor.

[0094] In one embodiment of any one of the aspects of the invention, if a KRAS G12 / G13 inhibitor is present, the KRAS G12 / G13 inhibitor is selected from the group consisting of Compound C, sotorasib (Amgen), adagrasib (Mirati), D-1553 (InventisBio), BI1701963 (Boehringer), GDC6036 (Roche), JNJ74699157 (J&J), X-Chem KRAS (X-Chem), LY3537982 (Lilly), BI1823911 (Boehringer), AS KRAS G12C (Ascentage Pharma), SF KRAS G12C (Sanofi), RMC032 (Revolution Medicine), JAB-21822 (Jacobio Pharmaceuticals), AST-KRAS G12C (Allist Pharmaceuticals), AZ KRAS G12C (Astra and KRAS G12C inhibitors selected from Zeneca), NYU-12VC1 (New York University), and RMC6291 (Revolution Medicines), or pharmaceutically acceptable salts thereof.

[0095] In one embodiment of any one of the aspects of the invention, when a KRAS G12 / G13 inhibitor is present, the KRAS G12 / G13 inhibitor is KRAS G12C inhibitor compound C (1-{6-[(4M)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl}prop-2-en-1-one) or AMG510, or a pharmaceutically acceptable salt thereof.

[0096] In one embodiment of any one of the aspects of the invention, when a KRAS G12 / G13 inhibitor is present, the KRAS G12 / G13 inhibitor is the KRAS G12C inhibitor Compound C, or a pharmaceutically acceptable salt thereof.

[0097] In one embodiment of any one of the aspects of the invention, if an SHP2 inhibitor is present, the SHP2 inhibitor is selected from the group consisting of TNO155 (Novartis), JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka X-37-SHP2 (X-37), or a pharmaceutically acceptable salt thereof.

[0098] In one embodiment of any one of the aspects of the invention, when an SHP2 inhibitor is present, the SHP2 inhibitor is TNO155, or a pharmaceutically acceptable salt thereof.

[0099] In an alternative embodiment, the SHP2 inhibitor, if present, is RMC-4550 or a pharmaceutically acceptable salt thereof, [ka] is.

[0100] In an alternative embodiment, the SHP2 inhibitor, if present, is RMC-4630 or a pharmaceutically acceptable salt thereof, [ka] is.

[0101] In one embodiment of any one of the aspects of the invention, when a cMET inhibitor is present, the cMET inhibitor is selected from the group consisting of crizotinib, capmatinib, tepotinib, AMG337, cabozantinib, savolitinib (AZD6094, HMPL-504), tivantinib, foretinib, voritinib, SU11274, PHA 665752, SGX523, BAY-853474, KRC-408, T-1840383, MK-2461, BMS-777607, JNJ-38877605, tivantinib (ARQ 197), PF-04217903, MGCD265, BMS-754807, BMS-794833, AMG-458, NVP-BVU972, AMG-208, golvatinib, norcantharidin, S49076, SAR125844, merestinib (LY2801653), onartuzumab, emibetuzumab, SAIT301, ABT-700, DN30, LY3164530, rilotumumab, ficlatuzumab, TAK701, and YYB-101, or a pharmaceutically acceptable salt thereof.

[0102] In one embodiment of any one of the aspects of the invention, when a cMET inhibitor is present, the cMET inhibitor is i) tepotinib, or ii) capmatinib, or a pharmaceutically acceptable salt thereof.

[0103] In one embodiment of any one of the aspects of the invention, when an EGFR inhibitor is present, the EGFR inhibitor is selected from the group consisting of cetuximab, panitumumab, erlotinib, gefitinib, osimertinib and nazartinib, or a pharmaceutically acceptable salt thereof.

[0104] In one embodiment of any one of the aspects of the invention, when an EGFR inhibitor is present, the EGFR inhibitor is nazartinib (also known as EGF816), or a pharmaceutically acceptable salt thereof.

[0105] In one embodiment of any one of the aspects of the invention, when a PI3K inhibitor is present, the PI3K inhibitor is selected from the group consisting of AMG511, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib, QAU421, and umbralisib, or a pharmaceutically acceptable salt thereof.

[0106] In one embodiment of any one of the aspects of the invention, when an MDM2 inhibitor is present, the MDM2 inhibitor is selected from the group consisting of nutlin-3a, idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademetan, and HDM201 (also known as silymarin), or a pharmaceutically acceptable salt thereof.

[0107] In one embodiment of any one of the aspects of the invention, when an MDM2 inhibitor is present, the MDM2 inhibitor is HDM201, or a pharmaceutically acceptable salt thereof.

[0108] In one embodiment of any one of the aspects of the invention, when a CDK4 / 6 inhibitor is present, the CDK4 / 6 inhibitor is selected from the group consisting of ribociclib, palbocyclib and abemaciclib, or a pharmaceutically acceptable salt thereof.

[0109] In one embodiment of any one of the aspects of the invention, when a CDK4 / 6 inhibitor is present, the CDK4 / 6 inhibitor is ribociclib, or a pharmaceutically acceptable salt thereof.

[0110] In one embodiment of any one of the aspects of the invention, when a MEK inhibitor is present, the MEK inhibitor is selected from the group consisting of pimasertib, PD-0325901, selumetinib, trametinib, binimetinib, and cobimetinib, or a pharmaceutically acceptable salt thereof.

[0111] In one embodiment of any one of the aspects of the invention, when a MEK inhibitor is present, the MEK inhibitor is trametinib, or a pharmaceutically acceptable salt thereof.

[0112] In one embodiment of any one of the aspects of the invention, when an ERK inhibitor is present, the ERK inhibitor is selected from the group consisting of ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 and BVD-523, or a pharmaceutically acceptable salt thereof.

[0113] In one embodiment of any one of the aspects of the invention, when an ERK inhibitor is present, the ERK inhibitor is LTT462 (linetarquib) or ulixertinib, or a pharmaceutically acceptable salt thereof.

[0114] In one embodiment of any one of the aspects of the invention, when a Raf inhibitor is present, the Raf inhibitor is selected from the group consisting of berbalafenib, naporafenib (also known as LXH254), encorafenib, vemurafenib and dabrafenib, or a pharmaceutically acceptable salt thereof.

[0115] In one embodiment of any one of the aspects of the invention, when a Raf inhibitor is present, the Raf inhibitor is dabrafenib or LXH254 (napolafenib), or a pharmaceutically acceptable salt thereof.

[0116] In one embodiment, the cancer is a TEAD-dependent cancer.

[0117] In one embodiment, the cancer is selected from the group consisting of breast cancer, lung cancer, ovarian cancer, kidney cancer, uterine cancer, colorectal cancer, malignant pleural mesothelioma, pancreatic cancer, prostate cancer, gastric cancer, gastrointestinal stromal tumor, esophageal cancer, liver cancer, medulloblastoma, head and neck cancer, sarcoma, squamous cell carcinoma, epithelioid hemangioendothelioma, ependymal tumor, and osteosarcoma.

[0118] In one embodiment, the TEAD inhibitor is administered on each of the first three days of a seven-day treatment cycle, and the treatment consists of at least two treatment cycles. In one embodiment, the daily dose of the TEAD inhibitor on each administration day is 15 mg to 100 mg. In one embodiment, the daily dose of the TEAD inhibitor on each administration day is 15, 30, 45, 60, 75 mg, 90 mg, or 100 mg.

[0119] definition The terms "a," "an," and "the," and similar references in the context of describing the present invention (particularly in the context of the claims below) should be construed to encompass both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. When the plural is used for compounds, patients, cancers, etc., this is construed to mean a single compound, patient, etc.

[0120] References herein to the "present invention" are intended to reflect certain inventive embodiments disclosed herein and should not be construed as unnecessarily limiting the claimed subject matter.

[0121] The term "synergistic effect" as used herein refers to the action of two or three therapeutic agents that produces an effect, for example, slowing the progression of a proliferative disease, particularly cancer, or its symptoms, that is greater than the simple sum of the effects of each drug administered alone. Synergistic effect can be calculated using suitable methods, such as the sigmoid-Emax equation (Holford, NHG and Scheiner, LB, Clin. Pharmacokinet. 6:429-453 (1981)), the Loewe additivity equation (Loewe, S. and Muischnek, H., Arch. Exp. Pathol Pharmacol. 114:313-326 (1926)), and the median-effect equation (Chou, TC and Talalay, P., Adv. Enzyme Regul. 22:27-55 (1984)). Each of the equations mentioned above can be applied to experimental data to generate corresponding graphs that help evaluate the effect of drug combinations. The corresponding graphs associated with the above-referenced equations are the concentration-effect curve, the isobologram curve, and the combination index curve, respectively.

[0122] The term "pharmaceutically acceptable salt" refers to salts that retain the biological effectiveness and properties of the compounds and that are typically not biologically or otherwise undesirable. The compounds may be capable of forming acid addition salts by virtue of the presence of an amino group.

[0123] Unless otherwise specified or clearly indicated by context, reference to therapeutic agents useful in the pharmaceutical combinations of the present invention includes both the free base of the compound and all pharmaceutically acceptable salts of the compound.

[0124] The term "combination" or "pharmaceutical combination" is defined herein to refer to either a fixed combination, a non-fixed combination, or a kit of elements in one unit dosage form for combined administration, where the therapeutic agents can be administered together, independently and simultaneously, or preferably separately within a time interval that allows the combination partners to exert a cooperative effect, e.g., a synergistic effect. Thus, the single compounds of the pharmaceutical combination of the present invention can be administered simultaneously or sequentially.

[0125] Furthermore, the pharmaceutical combination of the present invention may be in the form of a fixed combination or in the form of a non-fixed combination.

[0126] The term "fixed combination" means that the therapeutic agents, eg, a single compound of the combination, are in the form of a single entity or dosage form.

[0127] The term "non-fixed combination" means that the therapeutic agents, e.g., single compounds of the combination, are administered to a patient as separate entities or dosage forms, either simultaneously or sequentially without specific time limitations, preferably such administration resulting in therapeutically effective levels of the two therapeutic agents within the body of a subject, e.g., a mammal or human, in need thereof.

[0128] The pharmaceutical combination may further comprise at least one pharmaceutically acceptable carrier.Accordingly, the present invention relates to a pharmaceutical composition comprising the pharmaceutical combination of the present invention and at least one pharmaceutically acceptable carrier.

[0129] As used herein, the term "carrier" or "pharmaceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, surfactants, antioxidants, preservatives (e.g., antibacterial, antifungal), isotonic agents, absorption delaying agents, salts, preservatives, drug stabilizers, binders, excipients, disintegrants, lubricants, sweeteners, flavoring agents, dyes, and the like, and combinations thereof, as known to those skilled in the art (see, e.g., Remington's Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990, pp. 1289-1329). Except insofar as any conventional carrier is incompatible with the active ingredient, its use in therapeutic or pharmaceutical compositions is contemplated.

[0130] The phrase "pharmaceutically acceptable" is used herein to refer to compounds, materials, compositions, and / or dosage forms that are suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, within the scope of sound medical judgment, commensurate with a reasonable benefit / risk ratio.

[0131] In general, the term "pharmaceutical composition" is defined herein to refer to a mixture or solution containing at least one therapeutic agent administered to a subject, e.g., a mammal or human. The pharmaceutical combinations of the present invention can be formulated in pharmaceutical compositions suitable for enteral or parenteral administration, e.g., in unit dosage forms such as sugar-coated tablets, tablets, capsules, or suppositories, or ampoules. Unless otherwise specified, they are prepared in a manner known per se, e.g., by various conventional mixing, milling, direct compression, granulation, sugar-coating, dissolving, lyophilization processes, or manufacturing techniques readily apparent to those skilled in the art. It will be understood that the unit content of a combination partner contained in an individual dose of each dosage form need not necessarily constitute an effective amount per se, since the required effective amount may be reached by administration of multiple dosage units. Pharmaceutical compositions may contain from about 0.1% to about 99.9%, preferably from about 1% to about 60%, of a therapeutic agent. Those skilled in the art can select one or more of the above-mentioned carriers based on the specific desired properties of the dosage form by routine experimentation and without undue burden. The amount of each carrier used may vary within ranges conventional in the art. The following references disclose techniques and excipients used in formulating oral dosage forms: The Handbook of Pharmaceutical Excipients, 4th edition, Rowe et al., Eds., American Pharmaceuticals Association (2003); and Remington: the Science and Practice of Pharmacy, 20th edition, Gennaro, Ed., Lippincott Williams & Wilkins (2003). Any of these additional conventional carriers can be incorporated into the oral dosage form by incorporating one or more conventional carriers into the initial mixture before or during granulation, or by combining one or more conventional carriers with granules containing the drug combination or individual drugs of the drug combination in the oral dosage form.In the latter embodiment, the combined mixture may be further blended, for example, by a V-blender, and then compressed or molded into a tablet, for example, a monolithic tablet, encapsulated, or filled into a sachet. Obviously, the pharmaceutical combination of the present invention may be used to manufacture a medicament.

[0132] The present invention relates to such pharmaceutical combinations or compositions which are particularly useful as medicines.

[0133] In particular, the combination or composition of the present invention may be applied in the treatment of cancer.

[0134] The present invention also relates to the use of a pharmaceutical combination or a pharmaceutical composition of the present invention for the preparation of a medicament for the treatment of cancer, and to a method for treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical combination according to the present invention, or a pharmaceutical composition according to the present invention.

[0135] The term "treatment" as used herein includes treatment that relieves, reduces, or alleviates at least one symptom in a subject, increases progression-free survival, overall survival, extends the duration of response, or delays the progression of a disease. For example, treatment can be a reduction in one or several symptoms of a disease or the complete eradication of a disease, such as cancer. Within the meaning of the present invention, the term "treatment" also refers to halting disease, delaying its onset (i.e., the period before clinical symptoms of the disease), and / or reducing the risk of disease onset or worsening in a patient, e.g., a mammal, and in particular, the patient is a human. The term "treatment" as used herein includes tumor growth inhibition, which incorporates direct inhibition of primary tumor growth and / or systemic inhibition of metastatic cancer cells.

[0136] The terms "subject," "individual," or "patient" are used interchangeably herein and refer to a vertebrate, preferably a mammal, more preferably a human. Mammals include, but are not limited to, murines, apes, humans, farm animals, sport animals, and pets.

[0137] The term "therapeutically effective amount" of a compound of the invention (e.g., a chemical or biological agent) refers to the amount of a compound of the invention that causes a biological or medical response in a subject, such as a reduction or inhibition of enzyme or protein activity, or that ameliorates symptoms, alleviates pathology, slows or retards disease progression, or prevents disease. In one embodiment, a therapeutically effective amount in vivo can range from about 0.1 to 500 mg / kg, or from about 1 to 100 mg / kg, depending on the route of administration.

[0138] As used herein, the terms "inhibit," "inhibition," or "inhibiting" refer to the alleviation or suppression of a given condition, symptom, or disorder, or disease, or a significant decrease in the baseline activity of a biological activity or process.

[0139] The optimal dosage of each combination partner for treating cancer can be determined empirically for each individual using known methods and will depend on various factors, including, but not limited to, the degree of progression of the disease; the individual's age, weight, overall health, sex, and dietary habits; the timing and route of administration; and other drugs the individual is taking. The optimal dosage can be established using routine tests and procedures well known in the art. The amount of each combination partner that can be combined with a carrier material to produce a single dosage form will vary depending on the individual being treated and the specific method of administration. In some embodiments, a unit dosage form containing the drug combination described herein will contain the amount of each drug of the combination that is typically administered when the drug is administered alone.

[0140] The frequency of administration can vary depending on the compound used and the particular condition being treated or prevented. Generally, use of the minimum dosage sufficient to provide effective treatment is preferred. Patients can generally be monitored for therapeutic effectiveness using assays suitable for the condition being treated or prevented, which will be well known to those of skill in the art.

[0141] As used herein, the term "TEAD-dependent cancer" refers to any cancer in which TEAD (i.e., TEAD1, TEAD2, TEAD3 and / or TEAD4), or mutants or variants thereof, are known to be implicated, for example, in cancers in which the Hippo pathway is genetically altered.

[0142] As used herein, the term "TEAD inhibitor" refers to a compound that has activity as an inhibitor of TEAD (i.e., TEAD1, TEAD2, TEAD3, and / or TEAD4), or a mutant or variant thereof, which can be assayed in vitro, in vivo, or in a cell line. 50 [μM] is <10, such as <5, for example <2, such as <1, for example <0.5, for example <0.2, such as <0.1 in the biochemical assay described in the examples, and / or in the reporter gene cell assay described in the examples, and / or in the proliferative cell assay described in the examples.

[0143] The YAP / TAZ-TEAD protein-protein interaction inhibitor described herein refers to a TEAD inhibitor that inhibits TEAD activity by inhibiting the interaction of the YAP / TAZ complex with TEAD. Hyperactivation of YAP / TAZ, which leads to TEAD activation, has been reported in many cancers, such as malignant pleural mesothelioma. Therefore, inhibiting the interaction between YAP / TAZ and TEAD is a promising mechanism for inhibiting TEAD activity.

[0144] YAP / TAZ-TEAD protein-protein interaction inhibitors of the present invention include, but are not limited to, compounds of formula (I), the synthesis of which is described herein. [ka] During the ceremony, W is O; and CH-R w Selected from; X is selected from CH; and N; Y is selected from CH; and N; Z is selected from CH; O; and NH; where Y is N and W is CH-R w and Z is O; A is, (i) phenyl (phenyl optionally substituted with halo; or haloC1-C3 alkoxy); (ii) a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S (the aromatic heterocyclic ring is optionally substituted with hydroxy; C1-C3 alkoxy; or oxo); and (iii) a halobenzodioxole moiety of the formula: [ka] Selected from; R w is selected from (i) hydrogen; (ii) hydroxy; (iii) C1-C3 alkoxy; (iv) hydroxy-C1-C3 alkyl; (v) C1-C3 alkyl; and (vi) C1-C3 alkoxy-C1-C3 alkyl; Q is (i)-C(R 7 )2-N(R 8 )-R1; (ii) a 9- or 10-membered partially saturated heteroaryl containing at least one N heteroatom; and (iii) a 4-, 5-, or 6-membered saturated heterocyclic ring containing at least one heteroatom or group of heteroatoms selected from N, O, S, -S(=O) and -S(=O)2, provided that at least one N heteroatom is present, and wherein the heterocyclic ring is unsubstituted or substituted with one or more substituents independently selected from hydroxy, C1-C3 alkyl, C1-C3 alkoxy, halo, and C1-C3 alkylene that form a bridge between two ring atoms of the saturated heterocyclic ring, thereby forming a bridged bicyclic structure; R1 is (i) hydrogen; (ii) optionally deuterated C1-C6 alkyl; and (iii) (CH2) 0~2 R 1a Selected from; R 1a(i) hydroxy C1-C4 alkyl; (ii) C1-C3 alkoxy; (iii) a 5- or 6-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O (the saturated heterocyclic ring is independently C1-C3 alkyl; (CH2) 0~1 C(O)di(C1-C3 alkyl)amino; SO2C1-C3 alkyl; C(O)C1-C3 alkyl; or optionally substituted one or more times with oxo; (iv) independently hydroxy; hydroxyC1-C4 alkyl; C1-C6 alkoxy; C(O)OC1-C3 alkyl; CO2H; SO2C1-C3 alkyl; haloC1-C3 alkyl; NHR 1b ;(CH2) 0~1 C(O)NR 1c R 1d C1-C6 alkyl; haloC1-C3 alkoxy-C1-C3 alkyl; halo; a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S; or two R 1e C-C cycloalkyl optionally substituted one or more times with a group; where two R bonded to the same carbon atom 1e together with the carbon atom to which they are attached form a 5-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O, or a C3-C6 cycloalkyl, wherein the saturated heterocyclic ring or cycloalkyl is optionally substituted with hydroxy or oxo; R 1b is selected from (i) C(O)C1-C3 alkyl; and (ii) SO2C1-C3 alkyl; R 1c and R 1d are each independently selected from: (i) hydrogen; (ii) C1-C3 alkyl; and (iii) hydroxy C1-C4 alkyl; R2 is selected from (i) hydrogen; and (ii) halo; R3 is selected from (i) halo; (ii) haloC1-C3 alkyl; and (iii) cyano; R4 is selected from (i) hydrogen; (ii) halo; and (iii) C1-C3 alkyl; R5 is (i) hydrogen; (ii) C3-C6 cycloalkyl; CO2H; SO2C1-C3 alkyl; a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S; or a 5- or 6-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O, the ring optionally substituted with C(O)C1-C3 alkyl; (iii) halo; (iv) hydroxy C1-C6 alkoxy (wherein alkoxy is optionally deuterated); (v) halo C1-C6 alkoxy optionally substituted with hydroxy; (vi) S-halo C1-C3 alkyl optionally substituted with hydroxy; (vii) C1-C3 alkoxy C1-C3 alkoxy; (viii) NR 5a R 5b (ix) C1-C3 alkyl; (x) a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S; and (xi) hydroxy; R 5a and R 5b are each independently selected from: (i) hydrogen; and (ii) C1-C3 alkyl; or R 5a and R 5b together with the nitrogen atom to which they are attached form a 5- or 6-membered saturated heterocyclic ring (the saturated heterocyclic ring optionally further bearing a hydroxy group); R6 is (i) hydrogen; (ii) cyano; (iii) C(O)NHR 6a ;(iv)NHR 6b and (v) C1-C3 alkoxy substituted with NH2 or hydroxy; R 6a is selected from (i) hydrogen; (ii) C1-C3 alkyl; (iii) C3-C6 cycloalkyl; (iv) a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S, wherein the aromatic heterocyclic ring is optionally substituted with C1-C3 alkyl; R 6b is C1-C3 alkyl substituted with NH2 or hydroxy; R7 are each independently selected from hydrogen and C1-C3 alkyl; R 8 is hydrogen or C1-C3-alkyl.

[0145] In one embodiment, the compound of formula (I) or a pharmaceutically acceptable salt thereof is of formula (Ia), (Ic), or (Id): [ka] It is of the type.

[0146] In one embodiment, X is selected from CH; and N; A, (i) phenyl (phenyl optionally substituted with halo; or haloC1-C3 alkoxy); (ii) a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S, preferably N and S, wherein the aromatic heterocyclic ring is optionally substituted with hydroxy; C1-C3 alkoxy; or oxo; and (iii) a halobenzodioxole moiety of the formula: [ka] Selected from; R w is selected from (i) hydrogen; (ii) hydroxy; (iii) C1-C3 alkoxy; (iv) hydroxy-C1-C3 alkyl; (v) C1-C3 alkyl; and (vi) C1-C3 alkoxy-C1-C3 alkyl; Q is (i)-C(R 7 )2-N(R 8 )-R 1(ii) a 9- or 10-membered partially saturated heteroaryl containing at least one N heteroatom; and (iii) a 4-, 5-, or 6-membered saturated heterocyclic ring containing at least one heteroatom selected from N, O, and S, provided that at least one N heteroatom is present, where N is optionally located alpha to the atom connecting Q to the remainder of the molecule, and where the heterocyclic ring is unsubstituted or substituted with one or more substituents independently selected from hydroxy, C1-C3 alkyl, C1-C3 alkoxy, halo, and methylene, forming a bridge between two ring atoms of the saturated heterocyclic ring, thereby forming a bridged bicyclic structure; R1 is hydrogen; C1-C6 alkyl; and (CH2) 0~2 R 1a is selected from, where: R 1a (i) C1-C3 alkoxy; (ii) independently hydroxy; hydroxyC1-C4 alkyl; C1-C4 alkoxy; C(O)OC1-C3 alkyl; CO2H; C(O)NR 1c R 1d ;C1-C6 alkyl;Halo;HaloC1-C3 alkoxy-C1-C3 alkyl;SO2C1-C3 alkyl;HaloC1-C3 alkyl;NHR 1b ;C(O)NR 1c R 1d a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S; or two R 1e group (wherein two R 1e (iii) a C3-C6 cycloalkyl optionally substituted one or more times with a 5-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O, or a C3-C6 cycloalkyl (wherein the saturated heterocyclic ring or cycloalkyl is optionally substituted with hydroxy or oxo) in which groups are bonded at the same carbon atom and, together with the carbon atom to which they are bonded, form a 5-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O (wherein the saturated heterocyclic ring or cycloalkyl is optionally substituted with hydroxy or oxo); (iv) a 5- or 6-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O (wherein the saturated heterocyclic ring is independently C1-C3 alkyl; (CH2) 0~1C(O)di(C1-C3 alkyl)amino; SO2C1-C3 alkyl; C(O)C1-C3 alkyl; or optionally substituted one or more times with oxo; R 1b is selected from C(O)C1-C3 alkyl; and SO2C1-C3 alkyl; R 1c and R 1d are each independently selected from: (i) hydrogen; (ii) C1-C3 alkyl; and (iii) hydroxy C1-C4 alkyl; R2 is hydrogen or halo; R3 is halo; haloC1-C3 alkyl; or cyano; R4 is selected from hydrogen; halo; and C1-C3 alkyl; R5 is selected from (i) hydrogen; (ii) halo-C1-C6 alkoxy optionally substituted with hydroxy; (iii) S-haloC1-C3 alkyl optionally substituted with hydroxy; (iv) C1-C3 alkoxyC1-C3 alkoxy; (v) C1-C6 alkoxy optionally substituted with SO2C1-C3 alkyl, C3-C6 cycloalkyl, CO2H, or a 5- or 6-membered saturated heterocyclic ring containing at least one heteroatom selected from N and O, the ring optionally substituted with C(O)C1-C3 alkyl; (vi) C1-C3 alkyl; (vii) hydroxyC1-C6 alkoxy; (viii) a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S, preferably at least one N heteroatom; and (ix) hydroxy; R6 is cyano; C(O)NHR 6a ;NHR 6b or C1-C3 alkoxy substituted with NH2 or hydroxy; R 6a is selected from (i) hydrogen; (ii) C1-C3 alkyl; (iii) C3-C6 cycloalkyl; and (iv) a 5- or 6-membered aromatic heterocyclic ring containing at least one heteroatom selected from N, O, and S, preferably at least one N heteroatom, wherein the aromatic heterocyclic ring is optionally substituted with C1-C3 alkyl; R6b is C1-C3 alkyl substituted with NH2 or hydroxy; R 7 are each independently selected from hydrogen and C1-C3 alkyl; R 8 is hydrogen or C1-C3 alkyl.

[0147] In one embodiment, X is selected from CH; and N; A is phenyl (phenyl optionally substituted with halo; or haloC1-C3 alkoxy); R w is selected from (i) hydrogen; (ii) C1-C3 alkoxy; (iii) hydroxy-C1-C3 alkyl; (iv) C1-C3 alkyl; and (v) C1-C3 alkoxy-C1-C3 alkyl; Q is (i)-C(R 7 )2-NH-R1; and (ii) a 4-, 5-, or 6-membered saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O, and S, provided that at least one N heteroatom is present, where N is alpha to the atom connecting Q to the remainder of the molecule, and where the heterocyclic ring is unsubstituted or substituted with one or more substituents independently selected from hydroxy, C1-C3 alkyl, and halo; R1 is (i) C1-C6 alkyl; and (ii) R 1a is selected from; R 1a are independently selected from hydroxy; C1-C6 alkyl; or C3-C6 cycloalkyl optionally substituted one or more times with halo; R2 is hydrogen or halo; R3 is a halo; R4 is selected from (i) hydrogen; and (ii) halo; R5 is selected from halo-C1-C6 alkoxy, hydroxy, C1-C6 alkoxy; and hydroxy-C1-C6 alkoxy; R6 is C(O)NHR 6a and; R 6ais selected from (i) hydrogen; and (ii) C1-C3 alkyl; R 7 are each independently selected from hydrogen and C1-C3 alkyl.

[0148] In one embodiment, X is selected from CH; and N; A is phenyl (phenyl optionally substituted with halo; or haloC1-C3 alkoxy), in particular unsubstituted phenyl; R w is selected from (i) hydrogen; and (ii) C1-C3 alkyl; Q is (i)-C(R 7 )2-NH-R1; and (ii) a 4-, 5-, or 6-membered saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N and O, provided that at least one N heteroatom is present and is alpha to the carbon atom attaching Q to the remainder of the molecule, wherein the heterocyclic ring is unsubstituted or substituted with one or more substituents independently selected from hydroxy, C1-C3 alkyl, and halo; R1 is (i) C1-C6 alkyl; and (ii) R 1a is selected from; R 1a are independently hydroxy; C1-C6 alkyl; or C3-C6 cycloalkyl optionally substituted one or more times with halo; R2 is halo, especially fluoro; R3 is halo, especially chloro; R4 is halo, especially fluoro; R5 is selected from C1-C6 alkoxy; and hydroxy C1-C6 alkoxy; R6 is C(O)NHR 6a and; R 6a is selected from (i) hydrogen; and (ii) C1-C3 alkyl; Each R 7 is hydrogen.

[0149] In one embodiment, the compound of formula (I) is (S)-(5-chloro-2,4-diphenyl-2,3-dihydrobenzofuran-2-yl)methanamine; N1-(2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluorophenyl)ethane-1,2-diamine; 2-(2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluorophenoxy)ethanamine; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluorobenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,4R)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-methylbenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-chlorobenzamide trifluoroacetate; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-chloro-3-fluorobenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3,4-difluorobenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-methoxyethoxy)benzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)benzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((R)-2-hydroxypropoxy)benzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((R)-2-fluoropropoxy)benzamide; 2-(3-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-carbamoyl-2-fluorophenoxy)acetic acid trifluoroacetate; 4-(((R)-4-acetylmorpholin-2-yl)methoxy)-2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluorobenzamide; 4-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-methoxynicotinamide; 4-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-6-(difluoromethoxy)-5-fluoronicotinamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(methylamino)benzamide; 2-((2S,4S)-5-chloro-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxy-N-methylbenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-N-cyclopropyl-3-fluoro-4-methoxybenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3,4-difluoro-N-(1-methyl-1H-pyrazol-5-yl)benzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxy-N-(pyridin-3-yl)benzamide; 2-((2S,4S)-5-chloro-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxy-N-methylbenzamide; 2-((2S,4S)-5-chloro-2-(((trans-4-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,4S)-5-chloro-2-(((cis-4-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; (trans)-4-((((2S,4S)-4-(6-carbamoyl-2-fluoro-3-methoxyphenyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-2-yl)methyl)amino)cyclohexanecarboxylic acid; (cis)-4-((((2S,4S)-4-(6-carbamoyl-2-fluoro-3-methoxyphenyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-2-yl)methyl)amino)cyclohexanecarboxylic acid; 2-((2R,4S)-2-(aminomethyl)-5-chloro-2-(thiazol-4-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-(2,2-difluorobenzo[d][1,3]dioxol-4-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluorobenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-(2-fluorophenyl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluorobenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(cyclopropylmethoxy)-3-fluorobenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(1,1-difluoro-2-hydroxyethoxy)-3-fluorobenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-methoxyethoxy)benzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,4R)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-((1,1-difluoro-2-hydroxyethyl)thio)benzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((methylsulfonyl)methoxy)benzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(3,3-difluoropropoxy)-3-fluorobenzamide; 4-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-methoxynicotinamide; 4-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)nicotinamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)-N-methylbenzamide; 4-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 4-((2S,4S)-5-chloro-6-fluoro-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-methoxyethoxy)nicotinamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 4-((2S,4S)-5-chloro-6-fluoro-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)nicotinamide; 2-((2S,4S)-5-chloro-2-(((cyclopropylmethyl)amino)methyl)-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)-N-methylbenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)-N-methylbenzamide; 4-((2S,4S)-5-chloro-6-fluoro-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((cis)-4-(methylsulfonyl)cyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((trans)-4-(methylsulfonyl)cyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((4-(fluoromethyl)-4-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-2-(((4-acetamidocyclohexyl)amino)methyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((4-(methylsulfonamido)cyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-2-(((4-(dimethylcarbamoyl)cyclohexyl)amino)methyl)-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((2-oxo-1-azaspiro[4.5]decan-8-yl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-2-(((1-(2-(dimethylamino)-2-oxoethyl)piperidin-4-yl)amino)methyl)-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((4-(hydroxymethyl)cyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((3-(2-hydroxypropan-2-yl)cyclobutyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((1-(methylsulfonyl)piperidin-4-yl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((trans)-3-(hydroxymethyl)cyclobutyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((cis)-3-(hydroxymethyl)cyclobutyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,4S)-5-chloro-2-((((2R,4r,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl)amino)methyl)-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,4S)-5-chloro-2-((((2R,4s,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl)amino)methyl)-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 4-((2S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-methoxynicotinamide; 4-((2S,4S)-5-chloro-6-fluoro-2-((((cis)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-methoxynicotinamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((cis)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(((R)-tetrahydrofuran-2-yl)methoxy)benzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(((R)-tetrahydrofuran-2-yl)methoxy)benzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-ethyl-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((cis)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-ethyl-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(1H-imidazol-1-yl)benzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((cis)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(1H-imidazol-1-yl)benzamide; 2-((2S,4S)-2-(((1-acetylpiperidin-4-yl)amino)methyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(pyrimidin-2-ylmethoxy)benzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((cis)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(pyrimidin-2-ylmethoxy)benzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-2-((tert-butylamino)methyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((R)-2-hydroxypropyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((S)-1-hydroxypropan-2-yl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((1-methylcyclopropyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((2-methoxyethyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((2-(2-oxopyrrolidin-1-yl)ethyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-2-((((trans)-4-(1H-tetrazol-1-yl)cyclohexyl)amino)methyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-2-(((trans-3-((difluoromethoxy)methyl)cyclobutyl)amino)methyl)-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((1S,3R,4R)-3-fluoro-4-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((1R,3S,4S)-3-fluoro-4-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((trans-3-fluorocyclobutyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((1R,3S)-3-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxy-1-methylcyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((6-hydroxyspiro[3.3]heptan-2-yl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-3-hydroxy-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-3-hydroxy-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-3-hydroxy-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-methoxyethoxy)benzamide; 2-((2R,3S,4S)-2-(aminomethyl)-5-chloro-3-hydroxy-2-(pyridin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2R,3S,4S)-2-(aminomethyl)-5-chloro-3-hydroxy-2-(6-methoxypyridin-2-yl)-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-3-hydroxy-2-(2-methoxypyridin-3-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-3-hydroxy-2-(2-oxo-1,2-dihydropyridin-3-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-3-hydroxy-2-(2-(trifluoromethoxy)phenyl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,3S,4S)-5-chloro-3-hydroxy-2-((((trans)-4-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-5-chloro-3-hydroxy-2-((((cis)-4-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2R,3S,4S)-5-chloro-3-hydroxy-2-((((trans)-4-hydroxycyclohexyl)amino)methyl)-2-(pyridin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2R,3S,4S)-5-chloro-3-hydroxy-2-((((cis)-4-hydroxycyclohexyl)amino)methyl)-2-(pyridin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,3S,4S)-5-chloro-2-((cyclobutylamino)methyl)-3-hydroxy-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-3-hydroxy-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-3-hydroxy-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,3S,4S)-5-chloro-2-((cyclobutylamino)methyl)-6-fluoro-3-hydroxy-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-3-hydroxy-2-((((trans)-4-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-3-hydroxy-2-((((cis)-4-hydroxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-3-methoxy-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxycyclohexyl)amino)methyl)-3-methoxy-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-((((cis)-4-hydroxycyclohexyl)amino)methyl)-3-methoxy-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-5-chloro-2-((((cis)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-5-chloro-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-methoxyethoxy)benzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 4-((2S,3S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-methoxyethoxy)nicotinamide; 2-((2R,3S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-3-methyl-2-(pyridin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2R,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-(pyridin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-methoxyethoxy)benzamide; 2-((2R,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-(pyridin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)-N-methylbenzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)benzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-((((cis)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)benzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-(((trans-4-hydroxycyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-((((cis)-4-hydroxycyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-methoxyethoxy)benzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-((((cis)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-methoxyethoxy)benzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-(((trans-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-(((cis-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,3S,4S)-5-chloro-2-((cyclobutylamino)methyl)-6-fluoro-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 4-((2S,3S,4S)-5-chloro-6-fluoro-2-((((trans-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)nicotinamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)benzonitrile; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-(((trans-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)-N-methylbenzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)-N-methylbenzamide; 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)benzamide; 2-(2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3,4-difluorophenoxy)ethan-1-ol; 2-((2R,3S,4S)-5-chloro-6-fluoro-2-(6-hydroxypyridin-2-yl)-3-methyl-2-((methylamino)methyl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2R,3S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-(pyridin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-methoxyethoxy)benzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-(pyridin-3-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,4R)-2-(aminomethyl)-2-phenyl-5-(trifluoromethyl)-2,3-dihydrobenzofuran-4-yl)-4-methoxybenzamide; 2-((2S,4R)-5-cyano-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxy-N-methylbenzamide; (S)-2-((((trans)-4-hydroxycyclohexyl)amino)methyl)-2,4-diphenyl-2,3-dihydrobenzofuran-5-carbonitrile; 2-((2S,4S)-2-(aminomethyl)-5-chloro-2-phenyl-2,3-dihydrofuro[2,3-b]pyridin-4-yl)-3-fluorobenzamide; 2-(2-(aminomethyl)-6-chloro-2-phenyl-2,3-dihydrobenzofuran-7-yl)-3-fluoro-4-methoxybenzamide; 2-(2-(aminomethyl)-5-chloro-2-phenylbenzo[d][1,3]dioxol-4-yl)-3-fluorobenzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenylindolin-4-yl)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-2-((cyclohexylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-3-hydroxy-2-((((cis)-4-methoxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-3-hydroxy-2-((((trans)-4-methoxycyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; Methyl (cis)-4-((((2S,4S)-4-(6-carbamoyl-2,3-difluorophenyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-2-yl)methyl)amino)cyclohexane-1-carboxylate; Methyl (trans)-4-((((2S,4S)-4-(6-carbamoyl-2,3-difluorophenyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-2-yl)methyl)amino)cyclohexane-1-carboxylate; 2-((2S,4S)-2-((((Trans)-4-carbamoylcyclohexyl)amino)methyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluorobenzamide; 2-((2S,4S)-2-((((cis)-4-carbamoylcyclohexyl)amino)methyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-2-((((trans)-4-(methylcarbamoyl)cyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-2-((((cis)-4-(methylcarbamoyl)cyclohexyl)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-2-((((cis)-3-(difluoromethyl)cyclobutyl)amino)methyl)-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,4S)-5-chloro-2-((((trans)-3-(difluoromethyl)cyclobutyl)amino)methyl)-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide; 2-((2S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy-1,1,2,2-d4)-N-methylbenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((methyl-d3)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-(((methyl-d3)amino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy-1,1,2,2-d4)benzamide; 2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide, 4-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide 2-((2S,3R,4S)-5-chloro-6-fluoro-3-(methoxymethyl)-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide, 2-((2S,3R,4S)-5-chloro-6-fluoro-3-(hydroxymethyl)-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide, 2-((2S,3S,4S)-5-chloro-6-fluoro-2-((((trans)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxy-2-methylpropoxy)benzamide, 2-((2S,4S)-2-(azetidin-2-yl)-5-chloro-6-fluoro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)-N-methylbenzamide, 2-((2S,3S,4S)-2-(azetidin-2-yl)-5-chloro-6-fluoro-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)-N-methylbenzamide, 2-((2S,3S,4S)-2-(azetidin-2-yl)-5-chloro-6-fluoro-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)-N-methylbenzamide, (2-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide, 2-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)benzamide, 2-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)-N-methylbenzamide, 2-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)-N-methylbenzamide, 4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide, 2-((4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-5-(methylcarbamoyl)pyridin-2-yl)oxy)acetic acid, 4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-hydroxy-N-methylnicotinamide, 2-((2S,4S)-5-chloro-6-fluoro-2-(4-hydroxypyrrolidin-2-yl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-4-(difluoromethoxy)-3-fluorobenzamide, 2-((2S,4S)-5-chloro-6-fluoro-2-(4-hydroxy-4-methylpyrrolidin-2-yl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)benzamide, (2S,4R)-2-((S)-5-chloro-6-fluoro-2,4-diphenyl-2,3-dihydrobenzofuran-2-yl)-4-fluoropyrrolidine, 2-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-piperidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)-N-methylbenzamide, (3-((S)-5-chloro-6-fluoro-2,4-diphenyl-2,3-dihydrobenzofuran-2-yl)morpholine, 2-((2S,4S)-5-chloro-6-fluoro-2-(morpholin-3-yl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide, 2-((2S,3S,4S)-5-chloro-6-fluoro-3-hydroxy-2-phenyl-2-(pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide, 2-((2S,3S,4S)-5-chloro-6-fluoro-3-methoxy-2-phenyl-2-(pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide, 2-((2S,3S,4S)-5-chloro-6-fluoro-3-methoxy-2-phenyl-2-(pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide, 2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-phenyl-2-(pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)benzamide, 2-((2S,4S)-2-(1-aminoethyl)-5-chloro-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide, 2-((2S,3S,4S)-2-(1-aminoethyl)-5-chloro-6-fluoro-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-(2-methoxyethoxy)benzamide, 2-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)indolin-4-yl)-3-fluoro-4-(2-hydroxyethoxy)benzamide, 2-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)indolin-4-yl)-3-fluoro-4-methoxybenzamide, 2-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)indolin-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)-N-methylbenzamide, 4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)indolin-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide, 2-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide; 2-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxy-N-methylbenzamide; and 2-((2S,3S,4S)-2-(aminomethyl)-5-chloro-6-fluoro-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide, or a pharmaceutically acceptable salt thereof.

[0150] In one embodiment, the compound of formula (I) is [ka] is.

[0151] In one embodiment, the compound of formula (I) is [ka] is. [ka]

[0152] In one embodiment, the compound of formula (I) is [ka] is.

[0153] In one embodiment, the compound of formula (I) is [ka] is.

[0154] In one embodiment, the compound of formula (I) is [ka] is.

[0155] In one embodiment, the compound of formula (I) is [ka] is.

[0156] In one embodiment, the compound of formula (I) is [ka] is.

[0157] In one embodiment, the compound of formula (I) is [ka] is.

[0158] In one embodiment, the compound of formula (I) is [ka] is.

[0159] In one embodiment, the compound of formula (I) is [ka] is.

[0160] In one embodiment, the compound of formula (I) is [ka] is.

[0161] In one embodiment, the compound of Formula (I) is (2P)-2-{(2S)-5-chloro-6-fluoro-2-[(methylamino)methyl]-2-phenyl-2,3-dihydro-1-benzofuran-4-yl}-3-fluoro-4-(2-hydroxyethoxy)-N-methylbenzamide, having the following structure: [ka] It has.

[0162] In one embodiment, the compound of Formula (I) is (2P)-2-[(2S)-5-chloro-6-fluoro-2-({[(1r,4S)-4-hydroxycyclohexyl]amino}methyl)-2-phenyl-2,3-dihydro-1-benzofuran-4-yl]-4-(difluoromethoxy)-3-fluorobenzamide, having the following structure: [ka] It has.

[0163] In one embodiment, the compound of Formula (I) is (2P)-2-[(2S,3S)-5-chloro-6-fluoro-3-hydroxy-2-({[(1r,4S)-4-hydroxycyclohexyl]amino}methyl)-2-phenyl-2,3-dihydro-1-benzofuran-4-yl]-4-(difluoromethoxy)-3-fluorobenzamide, having the following structure: [ka] It has.

[0164] In one embodiment, the compound of Formula (I) is (2P)-2-[(2S,3S)-5-chloro-6-fluoro-2-({[(1r,4S)-4-hydroxy-4-methylcyclohexyl]amino}methyl)-3-methyl-2-phenyl-2,3-dihydro-1-benzofuran-4-yl]-3-fluoro-4-[(2S)-2-hydroxypropoxy]benzamide, having the following structure: [ka] It has.

[0165] In one embodiment, the compound of Formula (I) is (2P)-2-[(2S,3S)-5-chloro-6-fluoro-2-({[(1r,4S)-4-hydroxy-4-methylcyclohexyl]amino}methyl)-3-methyl-2-phenyl-2,3-dihydro-1-benzofuran-4-yl]-3-fluoro-4-(2-hydroxyethoxy)benzamide, having the following structure: [ka] It has.

[0166] In one embodiment, the compound of Formula (I) is (2P)-2-[(2S,3S)-5-chloro-6-fluoro-2-({[(1r,4S)-4-hydroxy-4-methylcyclohexyl]amino}methyl)-3-methyl-2-phenyl-2,3-dihydro-1-benzofuran-4-yl]-3-fluoro-4-[(2S)-2-hydroxypropoxy]benzonitrile, having the following structure: [ka] It has.

[0167] In one embodiment, the compound of Formula (I) is (2P)-2-[(2S,3S)-5-chloro-6-fluoro-2-({[(1r,4S)-4-hydroxy-4-methylcyclohexyl]amino}methyl)-3-methyl-2-phenyl-2,3-dihydro-1-benzofuran-4-yl]-3-fluoro-4-(2-hydroxyethoxy)-N-methylbenzamide, having the following structure: [ka] It has.

[0168] In one embodiment, the compound of Formula (I) is (2P)-2-{(2S,3S)-5-chloro-6-fluoro-3-methyl-2-[(methylamino)methyl]-2-phenyl-2,3-dihydro-1-benzofuran-4-yl}-3-fluoro-4-[(2S)-2-hydroxypropoxy]-N-methylbenzamide, having the following structure: [ka] It has.

[0169] In one embodiment, the compound of Formula (I) is (2P)-2-{(2S,3S)-5-chloro-6-fluoro-3-methyl-2-[(methylamino)methyl]-2-phenyl-2,3-dihydro-1-benzofuran-4-yl}-3-fluoro-4-methoxybenzamide, having the following structure: [ka] It has.

[0170] In one embodiment, the compound of Formula (I) is (4P)-4-{(2S,3S)-5-chloro-6-fluoro-3-methyl-2-[(methylamino)methyl]-2-phenyl-2,3-dihydro-1-benzofuran-4-yl}-5-fluoro-6-(2-hydroxyethoxy)-N-methylpyridine-3-carboxamide, which has the following structure: [ka] It has.

[0171] In one embodiment, the compound of Formula (I) is (4P)-4-{(2S)-5-chloro-6-fluoro-2-phenyl-2-[(2S)-pyrrolidin-2-yl]-2,3-dihydro-1-benzofuran-4-yl}-5-fluoro-6-(2-hydroxyethoxy)-N-methylpyridine-3-carboxamide, having the following structure: [ka] It has.

[0172] In one embodiment, the compound of Formula (I) is (2P)-2-{(2S)-5-chloro-6-fluoro-2-phenyl-2-[(2S)-pyrrolidin-2-yl]-2,3-dihydro-1H-indol-4-yl}-3-fluoro-4-(2-hydroxyethoxy)benzamide, having the following structure: [ka] It has.

[0173] As used herein, the term compound F refers to [ka] Refers to...

[0174] As used herein, the term compound G refers to [ka] Refers to...

[0175] As used herein, the term compound D refers to [ka] Refers to...

[0176] As used herein, the term compound E refers to [ka] Refers to...

[0177] As used herein, the term Compound A refers to [ka] Refers to...

[0178] As used herein, the term compound H refers to [ka] Compound H is also known as VT-104, CAS# 2417718-25-1. The synthesis of Compound H is described in WO 2020 / 097389. [ka]

[0179] In one embodiment, the TEAD inhibitor is Compound A, Compound B, Compound F, Compound G, Compound D, Compound E, Compound H, VT3989 (Vivace Therapeutics), and any of the compounds described in WO 201753706, WO 2017064277, WO 2017058716, WO 2018185266, WO 2018204532, WO 2019040380, WO 2019113236, WO 2019171268, WO 2019222431, WO 2019232216, WO 2019232225, WO 2019232226, WO 2019232227, WO 2019232224 ... and pharmaceutically acceptable salts thereof.

[0180] International Publication No. 201753706, International Publication No. 2017064277, International Publication No. 2017058716, International Publication No. 2018185266, International Publication No. 2018204532, International Publication No. 2019040380, International Publication No. 2019113236, International Publication No. 2019171268, International Publication No. 2019222431, International Publication No. 2019232216, International Publication No. 20 Each of WO20097389, WO2014734, WO2020051099, WO2020243415, WO2020243423, WO2021097110, WO2021102204, WO2021133896 and WO2022087008, and the TEAD inhibitors disclosed therein, are incorporated by reference.

[0181] In one embodiment, the TEAD inhibitor is Compound A, Compound B, Compound F, Compound G, Compound D, Compound E, Compound H, VT3989 (Vivace Therapeutics), 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one, (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one, (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one, (methyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one, (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide, N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide, (S)-N-(1-(pyridin-2-yl)ethyl) -5-(4-(trifluoromethyl)phenoxy)-2-naphthamide, N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide, (S)-N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide, (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2- naphthamide, (S)—N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide, (S)—N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide, N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide, and pharmaceutically acceptable salts thereof.

[0182] In an alternative embodiment, the TEAD inhibitor is: [ka] This inhibitor is disclosed in WO 2022 / 159986 and WO 2020 / 243415.

[0183] Some particularly preferred combinations include the following combinations: According to a further aspect of the invention, provided herein is a method of treating cancer in a patient in need thereof, comprising administering to said patient any of the following combinations: According to a further aspect of the invention, provided herein is any of the compounds listed in the following combinations for use in the treatment of cancer, wherein said treatment further comprises the administration of another combination partner.

[0184] combination VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof and a cMET inhibitor (e.g., capmatinib or tepotinib, e.g., capmatinib) or a pharmaceutically acceptable salt thereof VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291 and Compound C, for example, a KRAS inhibitor selected from the group consisting of Compound C, sotorasib, or adagrasib, or a pharmaceutically acceptable salt thereof) and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189(InnoCare), HBI2376(HUYA Bioscience), ETS001(Shanghai ETERN Biopharma), TAS-ASTX(Taiho & Otsuka Pharmas& Otsuka Pharmas), X-37-SHP2(X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or pharmaceutically acceptable salts thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Compound C, sotorasib, or adagrasib). VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademetan, or hdm201 (also known as silymarin)). VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib). VT3989 (Vivace Therapeutics) or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). · [ka] or a pharmaceutically acceptable salt thereof and a cMET inhibitor (e.g., capmatinib or tepotinib, e.g., capmatinib) or a pharmaceutically acceptable salt thereof · [ka] or a pharmaceutically acceptable salt thereof and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof · [ka] or a pharmaceutically acceptable salt thereof and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a KRAS inhibitor or [ka] ) · [ka] or a pharmaceutically acceptable salt thereof, and SHP2 inhibitors or pharmaceutically acceptable salts thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas) and X-37-SHP2 (X-37), [ka] ) · [ka] or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Compound C, sotorasib, or adagrasib). · [ka] or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). · [ka] or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) · [ka] or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib, or a pharmaceutically acceptable salt thereof). · [ka] or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). · [ka] or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., nutlin-3a, idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademetan, or hdm201 (also known as silymarin)). · [ka] or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). · [ka] or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). · [ka] or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib). · [ka] or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). Compound B or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) Compound B or a pharmaceutically acceptable salt thereof and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof Compound B or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C selected from the group consisting of sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib) G12 / G13 inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas), X-37-SHP2(X-37), [ka] an SHP2 inhibitor selected from the group consisting of [ka] ) Compound B or a pharmaceutically acceptable salt thereof and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and compound C, e.g., a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of compound C, sotorasib, or adagrasib). Compound B or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). Compound B or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) Compound B or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib, or a pharmaceutically acceptable salt thereof). Compound B or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). Compound B or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethan, or hdm201 (also known as silymarin) Compound B or a pharmaceutically acceptable salt thereof and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib or a pharmaceutically acceptable salt thereof). Compound B or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). Compound B or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib). Compound B or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). Compound A or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) Compound A or a pharmaceutically acceptable salt thereof and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof Compound A or a pharmaceutically acceptable salt thereof (e.g., a KRAS inhibitor selected from the group consisting of sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib) G12 / G13 inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas), X-37-SHP2(X-37), [ka] an SHP2 inhibitor selected from the group consisting of Compound A or a pharmaceutically acceptable salt thereof and SHP2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas) and X-37-SHP2 (X-37), [ka] ) Compound A or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and compound C, e.g., a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of compound C, sotorasib, or adagrasib). Compound A or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). Compound A or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) Compound A or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib, or a pharmaceutically acceptable salt thereof). Compound A or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). Compound A or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethan, or hdm201 (also known as silymarin) Compound A or a pharmaceutically acceptable salt thereof and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib or a pharmaceutically acceptable salt thereof). Compound A or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). Compound A or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). Compound A or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). Compound D or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) Compound D or a pharmaceutically acceptable salt thereof and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof Compound D or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C selected from the group consisting of sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib) G12 / G13 inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas), X-37-SHP2(X-37), [ka] an SHP2 inhibitor selected from the group consisting of Compound D or a pharmaceutically acceptable salt thereof and SHP2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas) and X-37-SHP2 (X-37), [ka] ) Compound D or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and compound C, e.g., a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of compound C, sotorasib, or adagrasib). Compound D or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). Compound D or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) Compound D or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib, or a pharmaceutically acceptable salt thereof). Compound D or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). Compound D or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethan, or hdm201 (also known as silymarin) Compound D or a pharmaceutically acceptable salt thereof and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib or a pharmaceutically acceptable salt thereof). Compound D or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). Compound D or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib). Compound D or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). Compound E or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) Compound E or a pharmaceutically acceptable salt thereof and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof Compound E or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB- [ka] or a pharmaceutically acceptable salt thereof) Compound E or a pharmaceutically acceptable salt thereof and SHP2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas) and X-37-SHP2 (X-37), [ka] ) Compound E or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of Compound C, sotorasib, or adagrasib). Compound E or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). Compound E or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) Compound E or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib, or a pharmaceutically acceptable salt thereof). Compound E or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). Compound E or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethan, or hdm201 (also known as silymarin) Compound E or a pharmaceutically acceptable salt thereof and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib or a pharmaceutically acceptable salt thereof). Compound E or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). Compound E or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib). Compound E or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). the compound F (2-((2S,3S)-5-chloro-6-fluoro-2-((((1r,4S)-4-hydroxy-4-methylcyclohexyl)amino)methyl)-3-methyl-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-((S)-2-hydroxypropoxy)benzamide) or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib); Compound F or a pharmaceutically acceptable salt thereof and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof [ka] ) Compound F or a pharmaceutically acceptable salt thereof and SHP2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas) and X-37-SHP2 (X-37), [ka] ) Compound F or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and compound C, e.g., a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of compound C, sotorasib, or adagrasib). Compound F or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). Compound F or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) Compound F or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib, or a pharmaceutically acceptable salt thereof). Compound F or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). Compound F or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethan, or hdm201 (also known as silymarin) Compound F or a pharmaceutically acceptable salt thereof and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib or a pharmaceutically acceptable salt thereof). Compound F or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). Compound F or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib). Compound F or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). Compound G or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) Compound G or a pharmaceutically acceptable salt thereof and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof Compound G or a pharmaceutically acceptable salt thereof (e.g., a KRAS G12C selected from the group consisting of sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib) G12 / G13 inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors (e.g., NO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas), X-37-SHP2(X-37), [ka] an SHP2 inhibitor selected from the group consisting of Compound G or a pharmaceutically acceptable salt thereof and SHP2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas) and X-37-SHP2 (X-37), [ka] ) Compound G or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and compound C, e.g., a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of compound C, sotorasib, or adagrasib). Compound G or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). Compound G or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) Compound G or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib, or a pharmaceutically acceptable salt thereof). Compound G or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). Compound G or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethan, or hdm201 (also known as silymarin) Compound G or a pharmaceutically acceptable salt thereof and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib or a pharmaceutically acceptable salt thereof). Compound G or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). Compound G or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib). Compound G or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of G12C, NYU-12VC1, RMC6291 and compound C, for example, compound C, sotorasib or adagrasib, and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2 (X-37), [ka] or a pharmaceutically acceptable salt thereof) 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and SHP2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas) and X-37-SHP2 (X-37), [ka] ) 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one and KRAS G12 / G13 inhibitors or pharmaceutically acceptable salts thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor selected from the group consisting of G12C, NYU-12VC1, RMC6291, and Compound C, such as Compound C, sotorasib, or adagrasib, or a pharmaceutically acceptable salt thereof 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethane, or hdm201 (also known as silymarin) 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). 3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of G12C, NYU-12VC1, RMC6291 and Compound C, for example, Compound C, sotorasib or adagrasib) and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2 (X-37), [ka] or a pharmaceutically acceptable salt thereof) (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and SHP2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas) and X-37-SHP2 (X-37), [ka] ) (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor selected from the group consisting of G12C, NYU-12VC1, RMC6291, and Compound C, such as Compound C, sotorasib, or adagrasib, or a pharmaceutically acceptable salt thereof (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib, or umbralisib, e.g., alpelisib) (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethane, or hdm201 (also known as silymarin) (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (R)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of G12C, NYU-12VC1, RMC6291 and Compound C, for example, Compound C, sotorasib or adagrasib) and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2 (X-37), [ka] or a pharmaceutically acceptable salt thereof) (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and SHP2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas) and X-37-SHP2 (X-37), [ka] ) (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor selected from the group consisting of G12C, NYU-12VC1, RMC6291, and Compound C, such as Compound C, sotorasib, or adagrasib, or a pharmaceutically acceptable salt thereof (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethane, or hdm201 (also known as silymarin) (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (S)-3-methyl-3-(5-(2-((4-(trifluoromethyl)phenyl)amino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of G12C, NYU-12VC1, RMC6291 and Compound C, for example, Compound C, sotorasib or adagrasib) and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2 (X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor selected from the group consisting of G12C, NYU-12VC1, RMC6291, and Compound C, such as Compound C, sotorasib, or adagrasib, or a pharmaceutically acceptable salt thereof (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethane, or hdm201 (also known as silymarin) (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (R)-N-(1-hydroxypropan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of G12C, NYU-12VC1, RMC6291 and Compound C, for example, Compound C, sotorasib or adagrasib) and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2 (X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor selected from the group consisting of G12C, NYU-12VC1, RMC6291, and Compound C, such as Compound C, sotorasib, or adagrasib, or a pharmaceutically acceptable salt thereof (N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethane, or hdm201 (also known as silymarin) N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., belbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib). N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). (S)-N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) (S)-N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof (S)-N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of G12C, NYU-12VC1, RMC6291 and Compound C, for example, Compound C, sotorasib or adagrasib) and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2 (X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) (S)-N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor selected from the group consisting of G12C, NYU-12VC1, RMC6291, and Compound C, such as Compound C, sotorasib, or adagrasib, or a pharmaceutically acceptable salt thereof (S)—N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). (S)—N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) (S)—N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (S)—N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). (S)-N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethane, or hdm201 (also known as silymarin) (S)-N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). (S)-N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). (S)—N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (S)—N-(1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of G12C, NYU-12VC1, RMC6291 and Compound C, for example, Compound C, sotorasib or adagrasib) and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2 (X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor selected from the group consisting of G12C, NYU-12VC1, RMC6291, and Compound C, such as Compound C, sotorasib, or adagrasib, or a pharmaceutically acceptable salt thereof N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethane, or hdm201 (also known as silymarin) N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., belbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). (S)-N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) (S)-N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof (S)-N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of G12C, NYU-12VC1, RMC6291 and Compound C, for example, Compound C, sotorasib or adagrasib) and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2 (X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) (S)-N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor selected from the group consisting of G12C, NYU-12VC1, RMC6291, and Compound C, such as Compound C, sotorasib, or adagrasib, or a pharmaceutically acceptable salt thereof (S)—N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). (S)-N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) (S)-N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (S)—N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). (S)-N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethane, or hdm201 (also known as silymarin) (S)-N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). (S)-N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). (S)-N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (S)-N-(3-hydroxy-1-(pyridin-2-yl)propyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of G12C, NYU-12VC1, RMC6291 and Compound C, for example, Compound C, sotorasib or adagrasib) and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2 (X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor selected from the group consisting of G12C, NYU-12VC1, RMC6291, and Compound C, such as Compound C, sotorasib, or adagrasib, or a pharmaceutically acceptable salt thereof (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, Mirademethane, or HDM201 (also known as Silymarin) (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (R)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of G12C, NYU-12VC1, RMC6291 and Compound C, for example, Compound C, sotorasib or adagrasib) and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2 (X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor selected from the group consisting of G12C, NYU-12VC1, RMC6291, and Compound C, such as Compound C, sotorasib, or adagrasib, or a pharmaceutically acceptable salt thereof (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethane, or hdm201 (also known as silymarin) (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., belbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (S)-N-(4-hydroxybutan-2-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). (S)-N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) (S)-N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof (S)-N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of G12C, NYU-12VC1, RMC6291 and Compound C, for example, Compound C, sotorasib or adagrasib) and an SHP2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2 (X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) (S)-N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and KRAS G12 / G13 inhibitors or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor selected from the group consisting of G12C, NYU-12VC1, RMC6291, and Compound C, such as Compound C, sotorasib, or adagrasib, or a pharmaceutically acceptable salt thereof (S)—N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). (S)-N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) (S)-N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). (S)—N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). (S)-N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethane, or hdm201 (also known as silymarin) (S)-N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor naphthamide selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). (S)-N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide naphthamide or a pharmaceutically acceptable salt thereof and Raf inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., velbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) (S)-N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide naphthamide or a pharmaceutically acceptable salt thereof and Raf inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and MEK inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., a MEK inhibitor naphthamide or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib). (S)-N-(2-hydroxy-1-(pyridin-2-yl)ethyl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide naphthamide or a pharmaceutically acceptable salt thereof and Raf inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib) and ERK inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462) N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamidenaphthamide or its pharmaceutically acceptable salt and MAPK pathway inhibitornaphthamide or its pharmaceutically acceptable salt N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide naphthamide or a pharmaceutically acceptable salt thereof and KRAS G12 / G13 inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor naphthamide or a pharmaceutically acceptable salt thereof selected from the group consisting of G12C, NYU-12VC1, RMC6291 and Compound C, for example Compound C, sotorasib or adagrasib) and an SHP2 inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2 (X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide naphthamide or a pharmaceutically acceptable salt thereof and KRAS G12 / G13 inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS a KRAS G12C inhibitor naphthamide selected from the group consisting of G12C, NYU-12VC1, RMC6291, and Compound C, such as Compound C, sotrasib, or adagrasib, or a pharmaceutically acceptable salt thereof N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide naphthamide or a pharmaceutically acceptable salt thereof and MEK inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor naphthamide or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib) N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462) N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor naphthamide or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethane, or hdm201 (also known as silymarin)). N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide naphthamide or a pharmaceutically acceptable salt thereof and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib or a pharmaceutically acceptable salt thereof). N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). N-(1,5-dihydroxypentan-3-yl)-5-(4-(trifluoromethyl)phenoxy)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors or pharmaceutically acceptable salts thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas), X-37-SHP2(X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitor or a pharmaceutically acceptable salt thereof) N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethan, or hdm201 (also known as silymarin) N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). 8-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) 8-Bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof 8-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors or pharmaceutically acceptable salts thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas), X-37-SHP2(X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) 8-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitor or a pharmaceutically acceptable salt thereof) 8-Bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). 8-Bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) 8-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). 8-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). 8-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethan, or hdm201 (also known as silymarin) 8-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). 8-Bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). 8-Bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). 8-Bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and Raf inhibitors or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and ERK inhibitors or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors or pharmaceutically acceptable salts thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas), X-37-SHP2(X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitor or a pharmaceutically acceptable salt thereof) 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethan, or hdm201 (also known as silymarin) 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). 8-amino-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors or pharmaceutically acceptable salts thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas), X-37-SHP2(X-37), [ka] or a pharmaceutically acceptable salt thereof) [ka] ) N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors or pharmaceutically acceptable salts thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas), X-37-SHP2(X-37), [ka] or a pharmaceutically acceptable salt thereof) N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and SHP2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas) and X-37-SHP2 (X-37), [ka] ) N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitor or a pharmaceutically acceptable salt thereof) N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethane, or hdm201 (also known as silymarin) N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., belbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). N-isopropyl-8-methyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). 8-ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) 8-Ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof 8-ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas), X-37-SHP2(X-37), [ka] an SHP2 inhibitor selected from the group consisting of [ka] ) 8-ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitor or a pharmaceutically acceptable salt thereof) 8-ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). 8-ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) 8-ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). 8-ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). 8-ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethan, or hdm201 (also known as silymarin) 8-ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). 8-ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). 8-ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). 8-ethyl-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). 8-cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) 8-Cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof 8-cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors or pharmaceutically acceptable salts thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas), X-37-SHP2(X-37), [ka] or a pharmaceutically acceptable salt thereof) 8-Cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and SHP2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas) and X-37-SHP2 (X-37), [ka] ) 8-cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitor or a pharmaceutically acceptable salt thereof) 8-Cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). 8-Cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) 8-cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). 8-Cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). 8-cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethan, or hdm201 (also known as silymarin) 8-cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). 8-Cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., belbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). 8-Cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., belbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). 8-Cyclopropyl-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., belbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) 8-Amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors or pharmaceutically acceptable salts thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas), X-37-SHP2(X-37), [ka] or a pharmaceutically acceptable salt thereof) 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and SHP2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas) and X-37-SHP2 (X-37), [ka] ) 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitor or a pharmaceutically acceptable salt thereof) 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an EGFR inhibitor or a pharmaceutically acceptable salt thereof (e.g., erlotinib, osimertinib, neratinib, gefitinib, cetuximab, panitumumab, lapatinib, dacomitinib, necitumumab, nazartinib, LTT462 or vandetanib, e.g., LTT462 or erlotinib). 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a PI3K inhibitor or a pharmaceutically acceptable salt thereof (e.g., AMG511, QAU421, buparlisib, idelalisib, copanlisib, duvelisib, alpelisib or umbralisib, e.g., alpelisib) 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462 or BVD-523, e.g., LTT462). 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and an MDM2 inhibitor or a pharmaceutically acceptable salt thereof (e.g., Nutlin-3a, Idasanutlin (also known as RG7388), RG7112, AMG-232 (also known as KRT-232), APG-115, BI-907828, milademethan, or hdm201 (also known as silymarin) 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a CDK4 / 6 inhibitor or a pharmaceutically acceptable salt thereof (e.g., a CDK4 / 6 inhibitor selected from the group consisting of palbocyclib, ribociclib, and abemaciclib, or a pharmaceutically acceptable salt thereof). 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., belbarafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib). 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., berbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and a MEK inhibitor or a pharmaceutically acceptable salt thereof (e.g., a MEK inhibitor or a pharmaceutically acceptable salt thereof selected from the group consisting of trametinib, binimetinib, selumetinib, pimasertib, PD-0325901, and cobimetinib, e.g., trametinib). 8-amino-7-bromo-N-isopropyl-5-(4-(trifluoromethyl)phenyl)-2-naphthamide or a pharmaceutically acceptable salt thereof, and a Raf inhibitor or a pharmaceutically acceptable salt thereof (e.g., velbalafenib, naporafenib, encorafenib, vemurafenib, or dabrafenib), and an ERK inhibitor or a pharmaceutically acceptable salt thereof (e.g., ulixertinib, GDC-0994, KO-947, Vtx-11e, SCH-772984, MK2853, LY3214996, MK08353, LTT462, or BVD-523, e.g., LTT462). 7-bromo-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and a cMET inhibitor or a pharmaceutically acceptable salt thereof (e.g., capmatinib or tepotinib, e.g., capmatinib) 7-Bromo-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a MAPK pathway inhibitor or a pharmaceutically acceptable salt thereof 7-bromo-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitors or pharmaceutically acceptable salts thereof) and SHP2 inhibitors or pharmaceutically acceptable salts thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka) Pharmas), X-37-SHP2(X-37), [ka] or a pharmaceutically acceptable salt thereof) 7-Bromo-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and SHP2 inhibitors or a pharmaceutically acceptable salt thereof (e.g., TNO155, JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai Blueray), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Erasca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharmas) and X-37-SHP2 (X-37), [ka] ) 7-bromo-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof, and a KRAS G12 / G13 inhibitor or a pharmaceutically acceptable salt thereof (e.g., sotorasib, adagrasib, LY349446, D-1553, BI1701963, GDC6036, JNJ74699157, X-Chem KRAS, LY3537982, BI1823911, AS KRAS G12C, SF KRAS G12C, RMC032, JAB-21822, AST-KRAS G12C, MRTX1257, AZ KRAS G12C, NYU-12VC1, RMC6291, and Compound C, e.g., Compound C, sotorasib, or adagrasib). G12C inhibitor or a pharmaceutically acceptable salt thereof) 7-bromo-N-isopropyl-5-[4-(trifluoromethyl)phenyl]naphthalene-2-carboxamide or a pharmaceutically acceptable salt thereof and an EGFR inhibi...

Claims

**Claim 1** A TEAD inhibitor for use in the treatment of cancer, wherein said treatment further comprises administration of a KRAS G12C inhibitor, wherein said TEAD inhibitor is a) (4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide) or a pharmaceutically acceptable salt thereof, or b) (2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide) or a pharmaceutically acceptable salt thereof and is a TEAD inhibitor selected therefrom. **Claim 2** i) a TEAD inhibitor selected from the following: a) (4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide) or a pharmaceutically acceptable salt thereof, or b) (2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide) or a pharmaceutically acceptable salt thereof ii) a KRAS G12C inhibitor and a combination comprising the same. **Claim 3** A KRAS G12C inhibitor for use in the treatment of cancer, wherein said treatment further comprises administration of a TEAD inhibitor, wherein said TEAD inhibitor is a) (4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide) or a pharmaceutically acceptable salt thereof, or b) (2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide) or a pharmaceutically acceptable salt thereof and is selected from a KRAS G12C inhibitor. **Claim 4** The TEAD inhibitor according to claim 1, wherein the treatment further comprises administration of an SHP2 inhibitor. **Claim 5** The combination according to claim 2, wherein the combination further comprises an SHP2 inhibitor. **Claim 6** An SHP2 inhibitor for use in the treatment of cancer, wherein the treatment further comprises administration of a TEAD inhibitor and a KRAS G12C inhibitor, wherein the TEAD inhibitor is a) (4-((2S,4S)-5-chloro-6-fluoro-2-phenyl-2-((S)-pyrrolidin-2-yl)-2,3-dihydrobenzofuran-4-yl)-5-fluoro-6-(2-hydroxyethoxy)-N-methylnicotinamide) or a pharmaceutically acceptable salt thereof, or b) (2-((2S,3S,4S)-5-chloro-6-fluoro-3-methyl-2-((methylamino)methyl)-2-phenyl-2,3-dihydrobenzofuran-4-yl)-3-fluoro-4-methoxybenzamide) or a pharmaceutically acceptable salt thereof selected from an SHP2 inhibitor. **Claim 7**: The KRAS G12C inhibitor is (1-{6-[(4M)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl}prop-2-en-1-one), sotorasib (Amgen), adagrasib (Mirati), D-1553 (InventisBio), BI1701963 (Boehringer), GDC6036 (Roche), JNJ74699157 (J&J), X-Chem KRAS (X-Chem), LY3537982 (Lilly), BI1823911 (Boehringer), AS KRAS G12C (Ascentage Pharma), SF KRAS G12C (Sanofi), RMC032 (Revolution Medicine), JAB-21822 (Jacobio Pharmaceuticals), AST-KRAS G12C (Allist Pharmaceuticals), AZ KRAS G12C (Astra Zeneca), NYU-12VC1 (New York University), and RMC6291 (Revolution Medicines), or a pharmaceutically acceptable salt thereof, and is the TEAD inhibitor according to claim 1. **Claim 8** The KRAS G12C inhibitor is (1-{6-[(4M)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl}prop-2-en-1-one) or AMG510, or a pharmaceutically acceptable salt thereof, and is the TEAD inhibitor according to claim 7. **Claim 9**: The KRAS G12C inhibitor is (1-{6-[(4M)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl}prop-2-en-1-one), or a pharmaceutically acceptable salt thereof, and is the TEAD inhibitor according to claim 8. **Claim 10** The TEAD inhibitor according to claim 4, wherein the SHP2 inhibitor is selected from the group consisting of TNO155 (Novartis), JAB3068 (Jacobio), JAB3312 (Jacobio), RLY1971 (Roche), SAR442720 (Sanofi), RMC4550 (Revolution Medicines), RMC4630 (Revolution Medicines), BBP398 (Navire), BR790 (Shanghai BlueRay), SH3809 (Nanjing Sanhome), PF0724982 (Pfizer), ERAS601 (Eraca), RX-SHP2 (Redx Pharma), ICP189 (InnoCare), HBI2376 (HUYA Bioscience), ETS001 (Shanghai ETERN Biopharma), TAS-ASTX (Taiho & Otsuka Pharma), and X-37-SHP2 (X-37), or a pharmaceutically acceptable salt thereof.

11. The TEAD inhibitor according to claim 10, wherein the SHP2 inhibitor is TNO155, or a pharmaceutically acceptable salt thereof.

12. The TEAD inhibitor according to claim 1, wherein the cancer is a TEAD-dependent cancer.

13. The TEAD inhibitor according to claim 1, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, ovarian cancer, kidney cancer, uterine cancer, colorectal cancer, malignant pleural mesothelioma, pancreatic cancer, prostate cancer, gastric cancer, gastrointestinal stromal tumor, esophageal cancer, liver cancer, medulloblastoma, head and neck cancer, sarcoma, squamous cell carcinoma, epitheloid hemangioendothelioma, epithelioma, and osteosarcoma.

14. The TEAD inhibitor according to claim 1, wherein the TEAD inhibitor is administered on each of the first 3 days of a 7-day treatment cycle, and the treatment consists of at least 2 treatment cycles.

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