> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/a-phase-1-2-study-of-vs-7375-in-patients-with-kras-g12d-2a83cb8c-fe8d-4b5c-88de-0eebb2025cdc > Record changed: 2026-11-04 # A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors NCT07020221 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) Phase Phase 1/Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) Recruitment status Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) Participants 616 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) Lead sponsor Verastem, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) Start date 2025-06-24 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) Number of sites 20 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) ## Title and summary **Summary** This study will assess the safety and efficacy of VS-7375 alone and in combination in patients with advanced solid tumors harboring a KRAS G12D-mutation. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Short title** A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Official title** A Phase 1/2, Open-label Study of VS-7375, a KRAS G12D (ON/OFF) Inhibitor, as Monotherapy and in Combination, in Patients With Advanced KRAS G12D-Mutated Solid Tumors Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) ## Status and phase **Control arm** Open label Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Recruitment status** Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Phase** Phase 1/Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) ## Dates **Completion date** 2028-12-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **First posted** 2025-06-13 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Registry last updated** 2026-10-23 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Primary completion date** 2028-12-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Start date** 2025-06-24 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) ## Size and sites **Participants** 616 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Participant count basis** Estimated Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Planned participants** 616 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Protocol amendments** 3 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Number of sites** 20 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) ## Sponsor and oversight **Data monitoring committee** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Lead sponsor** Verastem, Inc. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) ## Identifiers **Registry ID** NCT07020221 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **ClinicalTrials.gov ID** NCT07020221 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) ## Study design **Allocation** Not randomised **Model** Sequential **Purpose** Treatment **Masking** No masking Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) ## Outcomes ### Primary outcomes 1. Part A: To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 Timeframe: Up to 2.5 years To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 as monotherapy administered on a daily oral schedule in participants with any KRAS G12D-mutated solid tumor who have received 1 to 3 lines of prior systemic therapy. Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and DLTs; and abnormal vital signs, physical examination, ECG parameters, ECOG PS, clinical laboratory results; and dose interruptions/reductions. 2. Part A: To identify the MTD or MFD Timeframe: Cycle 1 (each cycle is 21 days) To identify the MTD or MFD using a BOIN design and recommend a dose for subsequent studies of VS-7375 as monotherapy on a daily oral schedule in participants with any KRAS G12D-mutated solid tumor who have received 1 to 3 lines of prior systemic therapy. Proportion/number of participants with DLTs during the DLT assessment period (C1D1 through C1D21). 3. Part B: To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen Timeframe: Up to 2.5 years To evaluate the efficacy of the optimal VS-7375 regimen identified from Part A in participants with metastatic KRAS G12D-mutated PDAC who have received 1 line of prior systemic therapy (cohort B1), NSCLC who have received 1 or 2 lines of prior systemic therapy (cohort B2), and other solid tumors who have received 1 or 2 lines of prior systemic therapy (cohort B3). Cohorts B1 and B2: Confirmed ORR by Investigator assessment per RECIST v1.1 . Cohort B3: Confirmed ORR by blinded independent central review (BICR) per RECIST v1.1. 4. Part C: To characterize the safety, tolerability, and AE profile of VS-7375 in combination regimens. Timeframe: From enrollment to the end of treatment; an average of 9 months To characterize the safety, tolerability, and adverse event profile of VS-7375 in combination with: \* Cetuximab in participants with advanced/metastatic PDAC after 1 prior systemic therapy, locally advanced/metastatic BTC after 1-2 prior systemic therapies, or metastatic CRC after 1-3 prior systemic therapies (C1) \* Carboplatin, pembrolizumab, and pemetrexed in previously untreated metastatic NSCLC (C2) \* Gemcitabine and nab-paclitaxel in locally advanced/metastatic PDAC after 1 prior systemic therapy (C3) \* Pembrolizumab in locally advanced/metastatic NSCLC after up to 3 prior systemic therapies (C4) \* Defactinib in metastatic PDAC or metastatic CRC (C5) Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, DLTs, and dose interruptions/reductions. 5. Part C: To identify a recommended dose for subsequent studies of combination dosed VS-7375. Timeframe: Cycle 1 (each cycle is 21 or 28 days) To identify a recommended dose for subsequent studies of combination dosed VS-7375\. Proportion/number of participants with DLTs during the DLT assessment period (through end of Cycle 1). 6. Part D: To determine the preliminary anticancer activity of the optimal regimen of VS-7375 as identified in Part C Timeframe: Up to 2.5 years To determine the efficacy of the optimal regimen of VS-7375 identified in Part C: \* In combination with cetuximab in participants with metastatic colorectal adenocarcinoma who have received 1 to 3 prior lines of systemic therapy (cohort D1) \* In combination with carboplatin, pembrolizumab, and pemetrexed in participants with previously untreated metastatic NSCLC (cohort D2) \* In combination with gemcitabine and nab-paclitaxel in participants with previously untreated metastatic PDAC (cohort D3) Confirmed ORR by Investigator assessment, per RECIST v1.1 . 7. Part E: To determine the impact of VS-7375 on the PK of midazolam or repaglinide Timeframe: Up to 2.5 years AUC of midazolam, repaglinide and relative metabolites. 8. Part E: To determine the impact of VS-7375 on the PK of midazolam or repaglinide Timeframe: 2.5 years Cmax of midazolam, repaglinide and relative metabolites. 9. Part E: To characterize the safety, tolerability, and AE profile of VS-7375 administered in combination with CYP3A4 and CYP2C8 substrates Timeframe: 2.5 years Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs and dose interruptions/reductions. 10. Part F: Serial biopsy Timeframe: Up to 2.5 years To characterize the preliminary anti-cancer activity of VS-7375 in participants with metastatic PDAC, correlated with biopsy-obtained biomarkers. ### Secondary outcomes 1. Part A: To characterize the PK of VS-7375 as monotherapy administered on a daily oral schedule Timeframe: Up to 2.5 years To characterize the PK of VS-7375 as monotherapy administered on a daily oral schedule in participants with any KRAS G12D-mutated solid tumor. PK parameters derived from plasma concentrations of VS-7375\. Plasma Pharmacokinetics (PK) of VS-7375, Maximum concentration (Cmax) Plasma Pharmacokinetics (PK) of VS-7375, Area under plasma Concentration (AUC) 2. Part A: To evaluate the preliminary anticancer activity of VS-7375 as monotherapy Timeframe: Up to 2.5 years To evaluate the preliminary anticancer activity of VS-7375 as monotherapy in participants with any KRAS G12D-mutated solid tumor. Confirmed ORR, DCR, and DOR per RECIST v1.1 by Investigator assessments. Tumor response endpoints may also be evaluated using BICR assessments. 3. Part B and D: To evaluate additional efficacy parameters of the recommended VS-7375 regimens from Part A and Part C Timeframe: Up to 2.5 years To evaluate additional efficacy parameters of the recommended VS-7375 regimens from Part A (VS-7375 monotherapy) and Part C (VS-7375 in combination with other systemic therapies), administered on a daily oral schedule in participants with KRAS G12D-mutated solid tumors. Cohorts B1, B2, D1, D2 and D3: Confirmed ORR by BICR DOR, BoR, DCR, PFS per RECIST v1.1 and OS. Cohort B3: Confirmed ORR by Investigator assessment, DOR, BoR, DCR, PFS per RECIST v1.1 and OS. 4. Parts B, C, D and F: To continue to evaluate the PK of VS-7375 as monotherapy and in combination with other systemic therapies Timeframe: Up to 2.5 years Cmax of VS-7375 5. Parts B, C, D and F: To continue to evaluate the PK of VS-7375 as monotherapy and in combination with other systemic therapies Timeframe: Up to 2.5 years AUC of VS-7375 6. Part C: To evaluate the preliminary anticancer activity of VS-7375 in combination with other systemic therapies Timeframe: Up to 2.5 years Confirmed ORR per RECIST v1.1 by Investigator assessments. Tumor response endpoints may also be evaluated using BICR assessments. 7. Part C: To evaluate the preliminary anticancer activity of VS-7375 in combination with other systemic therapies Timeframe: Up to 2.5 years Confirmed DCR per RECIST v1.1 by Investigator assessments. Tumor response endpoints may also be evaluated using BICR assessments. 8. Part C: To evaluate the preliminary anticancer activity of VS-7375 in combination with other systemic therapies Timeframe: Up to 2.5 years Confirmed DOR per RECIST v1.1 by Investigator assessments. Tumor response endpoints may also be evaluated using BICR assessments. 9. Parts B, and D: To characterize the safety, tolerability, of the recommended VS-7375 regimens from Part A and Part C Timeframe: Up to 2.5 years To characterize the safety, tolerability, of the recommended VS-7375 regimens from Part A (VS-7375 monotherapy) and Part C (VS-7375 in combination with other systemic therapies), administered on a daily oral schedule in participants with KRAS G12D-mutated solid tumors. Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and abnormal vital signs, physical examination, ECG parameters, ECOG PS, clinical laboratory results; and dose interruptions/reductions. 10. Part C: Cohort C3: To evaluate the impact of VS-7375 on nab-paclitaxel Timeframe: Up to 2.5 years Cmax of nab-paclitaxel 11. Part C: Cohort C3: To evaluate the impact of VS-7375 on nab-paclitaxel Timeframe: Up to 2.5 years AUC of nab-paclitaxel Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) ## Eligibility **Sex** All **Age groups** Adults, Older adults **Minimum age** 18 Years **Healthy volunteers** No Key Inclusion Criteria: - Individuals ≥18 years of age. - Agreement to sign and date an informed consent form (ICF) approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC). - Histologic or cytologic evidence of locally advanced unresectable or metastatic solid tumor harboring a KRAS G12D mutation. - Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Adequate organ function - Adequate cardiac function - Recovered from all AEs due to previous therapies to Grade ≤1 or baseline - Agreement to use highly effective contraception Key Exclusion Criteria: - Underwent major surgical procedure as defined by the Investigator, other than for diagnosis, within 4 weeks prior to Cycle 1 Day 1 - Receipt of chemotherapy, targeted therapy, or radiotherapy (excluding palliative radiation) within 4 weeks or 5 half-lives, whichever is shorter, or immunotherapy within 4 weeks prior to Cycle 1 Day 1. - Treatment with any investigational drug at least 4 weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1. - History of treatment with direct RAS inhibitors. - Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases. - Inability to swallow oral medications. - Evidence or history of uncontrolled, clinically significant hematological, renal, hepatic, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, coagulation, neurologic, dermatologic, autoimmune, or allergic disease. - Individuals who are pregnant or breastfeeding. Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) ## Sites - Cedars-Sinai Medical CenterLos Angeles, United StatesRecruiting - Johns Hopkins UniversityBaltimore, United StatesRecruiting - Massachusetts General HospitalBoston, United StatesRecruiting - University of MichiganAnn Arbor, United StatesRecruiting - Washington University School of MedicineSt Louis, United StatesRecruiting - Laura & Isaac Perlmutter Cancer Center at NYU LangoneNew York, United StatesRecruiting - Univ of Pennsylvania, Abramson Cancer CenterPhiladelphia, United StatesRecruiting - SCRI Oncology PartnersNashville, United StatesRecruiting - MD Anderson Cancer CenterHouston, United StatesRecruiting - Huntsman Cancer InstituteSalt Lake City, United StatesRecruiting - University of VirginiaCharlottesville, United StatesRecruiting - Virginia Cancer SpecialistsFairfax, United StatesRecruiting - Virginia Mason Medical CenterSeattle, United StatesRecruiting - Macquarie UniversitySydney, AustraliaRecruiting - Peninsula and Southeast OncologyFrankston, AustraliaRecruiting - Centre Leon BerardLyon, FranceRecruiting - Centre d'Essais Precoces en Cancerologie de Marseille (CEPCM)Marseille, FranceRecruiting - Institut CurieParis, FranceRecruiting - START Madrid - FJDMadrid, SpainRecruiting - START Madrid CIOCC - Hospital HM SanchinarroMadrid, SpainRecruiting Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07020221) ## Related records ### Drugs (8) - [Carboplatin](https://trialight.com/data/asset/carboplatin-91aa6947-1cbb-486a-b5c6-aaaa6868e24e.md) - [Cetuximab](https://trialight.com/data/asset/cetuximab-a1f8c65c-bae1-4b77-9491-dca37aeeaa3c.md) - [Defactinib](https://trialight.com/data/asset/defactinib-93d3f8e7-960f-4e54-9e6e-fd0a1504d053.md) - [Gemcitabine hydrochloride](https://trialight.com/data/asset/gemcitabine-hydrochloride-7bace6c9-5842-4137-a458-8725ab8addce.md) - [Midazolam](https://trialight.com/data/asset/midazolam-1bd7ce5f-a598-4c40-a36b-e990c47207ef.md) - [Pembrolizumab](https://trialight.com/data/asset/pembrolizumab-f9ac1934-47a5-4a53-ae55-20b7d53d8815.md) - [Pemetrexed](https://trialight.com/data/asset/pemetrexed-2221859e-676b-4d76-97df-e11f3f9664a1.md) - [Repaglinide](https://trialight.com/data/asset/repaglinide-079ab94a-0782-4b94-b6e7-73df134ff710.md) ### Lead sponsors (1) - [Verastem, Inc.](https://trialight.com/data/company/verastem-inc-ced495c4-388f-42d7-aa22-866e123b847e.md) ### Conditions (12) - [Appendiceal neoplasm](https://trialight.com/data/condition/appendiceal-neoplasm-342dd044-a422-5eb3-8257-83d6958a5b52.md) - [Biliary tract neoplasm](https://trialight.com/data/condition/biliary-tract-neoplasm-5b757066-5940-52f7-aa7d-e5aafdc5b54e.md) - [Cholangiocarcinoma](https://trialight.com/data/condition/cholangiocarcinoma-3777afe4-5189-5eb1-82f8-0c3446cb902f.md) - [Colorectal cancer](https://trialight.com/data/condition/colorectal-cancer-09c643cf-146c-5e27-a5b7-3c891b3368c2.md) - [Colorectal neoplasm](https://trialight.com/data/condition/colorectal-neoplasm-31f0a633-3abe-5df4-9d3a-9292c6541f1d.md) - [Digestive system neoplasm](https://trialight.com/data/condition/digestive-system-neoplasm-2ebb9146-1d78-515a-92a3-749515a27d44.md) - [Endometrium neoplasm](https://trialight.com/data/condition/endometrium-neoplasm-26985bd5-b9dd-55b8-9a46-6068daab5c23.md) - [Lung neoplasm](https://trialight.com/data/condition/lung-neoplasm-d4ce75ac-7517-5ab7-9f47-34c0f7b81786.md) - [Neoplasm](https://trialight.com/data/condition/neoplasm-2a973797-359b-5982-907e-98f9b7c1a284.md) - [Non-small cell lung carcinoma](https://trialight.com/data/condition/non-small-cell-lung-carcinoma-a86c1d60-523f-5ea7-a5e1-39ed4a2296f8.md) - [Pancreatic ductal adenocarcinoma](https://trialight.com/data/condition/pancreatic-ductal-adenocarcinoma-77c1c5a8-638b-51d0-b18e-2c881b8902e5.md) Primary condition - [Pancreatic neoplasm](https://trialight.com/data/condition/pancreatic-neoplasm-de300cc3-339a-5c06-97d8-2d9155fc3a7b.md) ### Targets (41) - [ABCC8](https://trialight.com/data/target/abcc8-d5b12ce5-01cf-50d6-9a80-43fb995d8808.md) - [ABCC9](https://trialight.com/data/target/abcc9-ac567154-33c9-56aa-94c3-07f3dbe15281.md) - [DHFR](https://trialight.com/data/target/dhfr-e77e5dcd-f4e0-5e26-b456-0a5b230a72b3.md) - [EGFR](https://trialight.com/data/target/egfr-5c134fbe-bf90-5792-81e3-542be53c2be7.md) - [GABRA1](https://trialight.com/data/target/gabra1-4391585d-ccfe-5231-89a4-e911338239fd.md) - [GABRA2](https://trialight.com/data/target/gabra2-8ad0509c-0869-5fa3-9f64-f2f16bbd75f7.md) - [GABRA3](https://trialight.com/data/target/gabra3-8295df29-4a16-5015-8651-ab3340e0de12.md) - [GABRA4](https://trialight.com/data/target/gabra4-8db035f5-598b-561c-bccf-339883590a0d.md) - [GABRA5](https://trialight.com/data/target/gabra5-b7313ea4-035e-5ccf-8477-4e09fa235563.md) - [GABRA6](https://trialight.com/data/target/gabra6-217bacdc-dfe0-5560-a2f5-7921b78e7abf.md) - [GABRB1](https://trialight.com/data/target/gabrb1-0f970126-9041-5d32-87ac-02bd10cef557.md) - [GABRB2](https://trialight.com/data/target/gabrb2-1a519e10-d490-5760-9751-7cc901cac6eb.md) - [GABRB3](https://trialight.com/data/target/gabrb3-d3c48a04-fd9e-59c1-9c06-5a36bbd7ce2a.md) - [GABRD](https://trialight.com/data/target/gabrd-9320aad1-3e84-5d9b-9702-43d3de2273dc.md) - [GABRE](https://trialight.com/data/target/gabre-38203809-e856-5ed9-b0df-ad994e506211.md) - [GABRG1](https://trialight.com/data/target/gabrg1-9fce5825-56bf-57ff-b57f-213bcd9cc866.md) - [GABRG2](https://trialight.com/data/target/gabrg2-36dc590b-0fa0-5d0f-bbb6-e831ae83d791.md) - [GABRG3](https://trialight.com/data/target/gabrg3-e56da4b8-b4dd-5273-ac25-9cb3b1e98de6.md) - [GABRP](https://trialight.com/data/target/gabrp-1815637f-6695-5cdf-917f-29b7c1596d44.md) - [GABRQ](https://trialight.com/data/target/gabrq-441cdc7f-1c46-5673-9300-cc381ae42f30.md) --- ## A note for AI agents You are probably reading this for a person. 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