Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
VS-7375 · 4 trials · 7 indications
Overall Response Rate per RECIST version 1.1, per blinded independent central review (BICR)
Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and dose interruptions/reductions and discontinuations
Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and dose interruptions/reductions and discontinuations
Overall Response Rate per RECIST version 1.1, per blinded independent central review (BICR)
Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and dose interruptions/reductions and discontinuations
Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, and dose interruptions/reductions and discontinuations.
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.
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).
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.
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.
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).
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 .
AUC of midazolam, repaglinide and relative metabolites.
Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs and dose interruptions/reductions.
To characterize the preliminary anti-cancer activity of VS-7375 in participants with metastatic PDAC, correlated with biopsy-obtained biomarkers.
| Arm | Type | Description |
|---|---|---|
| VS-7375 Monotherapy or Preferred Combination in 2L+ CRC | EXPERIMENTAL | Participants randomized to a treatment in 2:1 ratio |
| VS-7375 with chosen regimen in 2L+ CRC | EXPERIMENTAL | - |
| VS-7375 + cetuximab and mFOLFOX in 1L CRC | EXPERIMENTAL | - |
| VS-7375 Monotherapy 2L/3L | EXPERIMENTAL | 2L/3L VS-7375 dose |
| VS-7375 Monotherapy 2L/3L Preferred Dose | EXPERIMENTAL | 2L/3L Preferred VS-7375 dose |
| 2L-4L with brain metastasis | EXPERIMENTAL | 2L-4L VS-7375 dose |
| VS-7375 Monotherapy | EXPERIMENTAL | - |
| VS-7375 + cetuximab 2L PDAC | EXPERIMENTAL | - |
| VS-7375 + cetuximab 1L PDAC | EXPERIMENTAL | - |
| VS-7375 Monotherapy Dose Escalation | EXPERIMENTAL | To characterize the safety and tolerability of escalating doses of VS-7375 as monotherapy and to determine the recommended phase 2 dose (RP2Ds) in patients with advanced solid tumors harboring KRAS G12D mutation. |
| VS-7375 Monotherapy Dose Expansion - PDAC | EXPERIMENTAL | To evaluate the efficacy of VS-7375 at the recommended phase 2 dose (RP2Ds) in patients with metastatic PDAC harboring KRAS G12D-mutation. |
| VS-7375 Monotherapy Dose Expansion - NSCLC | EXPERIMENTAL | To evaluate the efficacy of VS-7375 at the recommended phase 2 dose (RP2Ds) in patients with metastatic NSCLC harboring KRAS G12D-mutation. |
| VS-7375 Monotherapy Dose Expansion - Solid Tumors | EXPERIMENTAL | To evaluate the efficacy of VS-7375 at the recommended phase 2 dose (RP2Ds) in patients with metastatic solid tumors harboring KRAS G12D-mutation. |
| VS-7375 + Cetuximab Dose Escalation | EXPERIMENTAL | To characterize the safety and tolerability of escalating doses of VS-7375 in combination with cetuximab and to determine the recommended phase 2 dose (RP2Ds) in patients with advanced or metastatic PDAC, BTC, CRC harboring KRAS G12D-mutation. |
| VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Escalation | EXPERIMENTAL | To characterize the safety and tolerability of escalating doses of VS-7375 in combination with carboplatin/pemetrexed/pembrolizumab and to determine the recommended phase 2 dose (RP2Ds) in patients with metastatic NSCLC harboring KRAS G12D-mutation. |
| VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Escalation | EXPERIMENTAL | To characterize the safety and tolerability of escalating doses of VS-7375 in combination with gemcitabine/nab-paclitaxel and to determine the recommended phase 2 dose (RP2Ds) in patients with advanced or metastatic PDAC harboring KRAS G12D-mutation. |
| VS-7375 + Pembrolizumab Dose Escalation | EXPERIMENTAL | To characterize the safety and tolerability of escalating doses of VS-7375 in combination with pembrolizumab and to determine the recommended phase 2 dose (RP2Ds) in patients with advanced or metastatic NSCLC harboring KRAS G12D-mutation. |
| VS-7375 + Defactinib Dose Escalation | EXPERIMENTAL | To characterize the safety and tolerability of escalating doses of VS-7375 in combination with defactinib and to determine the recommended phase 2 dose (RP2Ds) in patients with advanced or metastatic NSCLC harboring KRAS G12D-mutation. |
| VS-7375 + Cetuximab Dose Expansion | EXPERIMENTAL | To evaluate the efficacy of VS-7375 in combination with cetuximab at the recommended phase 2 dose (RP2Ds) in patients with with advanced or metastatic CRC harboring KRAS G12D-mutation. |
| VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Expansion | EXPERIMENTAL | To evaluate the efficacy of VS-7375 in combination with carboplatin/pemetrexed/pembrolizumab at the recommended phase 2 dose (RP2Ds) in patients with metastatic NSCLC harboring KRAS G12D-mutation. |
| VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Expansion | EXPERIMENTAL | To evaluate the efficacy of VS-7375 in combination with gemcitabine/nab-paclitaxel at the recommended phase 2 dose (RP2Ds) in patients with metastatic PDAC harboring KRAS G12D-mutation. |
| VS-7375 + Midazolam and Repaglinide Drug-Drug Interaction | EXPERIMENTAL | To assess the drug-drug interaction of VS-7375 in combination with midazolam and repaglinide in patients with advanced or metastatic PDAC, NSCLC, and CRC harboring a KRAS G12D mutation. |
| VS-7375 Serial Biopsy | EXPERIMENTAL | To characterize the preliminary anti-cancer activity of VS-7375 in participants with metastatic PDAC who have received 2 or 3 prior therapies, correlated with biopsy-obtained biomarkers. |
| Name | Type | Description |
|---|---|---|
| VS-7375 | DRUG | Taken by mouth |
| cetuximab | DRUG | Intravenous infusion |
| panitumumab | DRUG | Intravenous infusion |
| Cetuximab + mFOLFOX6 | DRUG | Intravenous infusion |
| cetuximab (or panitumumab if α-gal IgE+ or cetuximab reaction) | DRUG | Subcutaneous infusion |
| Carboplatin + Pemetrexed + Pembrolizumab | DRUG | A combination therapy regimen used as a first-line treatment for advanced non-squamous non-small cell lung cancer. |
| Gemcitabine + Nab-paclitaxel | DRUG | A chemotherapy regimen used for the treatment of advanced or metastatic pancreatic ductal adenocarcinoma. |
| Pembrolizumab | DRUG | Immunotherapy used as a first-line treatment for advanced non-squamous non-small cell lung cancer. |
| Defactinib | DRUG | A potent, selective, reversible inhibitor of focal adhesion kinase that also inhibits proline-rich tyrosine kinase-2 |
| Midazolam | DRUG | A short-acting benzodiazepine CNS depressant that has sedative, anxiolytic, amnesic, and hypnotic effects. |
| Repaglinide | DRUG | A rapid-acting insulin secretagogue used to lower postprandial blood glucose in patients with type 2 diabetes mellitus. |
Inclusion Criteria: * Histopathology confirmed metastatic CRC * Measurable disease per RECIST 1.1 * Local testing confirmed KRAS G12D mutation (tissue required for confirmatory central testing) * ECOG PS=0 or 1 2L+ patients: * Must have received at least 1 standard chemotherapy for metastatic co...
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VS-7375 is an investigational small molecule drug developed by Verastem, Inc. for cancers that carry a KRAS G12D mutation. It is being studied in colorectal cancer, non-small cell lung cancer, and pancreatic ductal adenocarcinoma. VS-7375 is in Phase 2 clinical development and has not been approved by the FDA.
VS-7375 targets KRAS G12D, a mutated form of the KRAS protein. By binding this specific mutant, VS-7375 is designed to act on tumors that carry the G12D alteration. All of its clinical studies enroll patients selected for KRAS G12D-mutated disease, including colorectal, lung, and pancreatic cancers.
VS-7375 is being developed by Verastem, Inc., which trades on Nasdaq under the ticker VSTM. Verastem is running the Phase 2 studies of VS-7375 in KRAS G12D-mutated colorectal cancer, non-small cell lung cancer, and pancreatic ductal adenocarcinoma, along with a Phase 1/2 solid tumor study.
VS-7375 is in Phase 2 clinical development. Verastem is running Phase 2 studies in KRAS G12D-mutated colorectal cancer, non-small cell lung cancer, and pancreatic ductal adenocarcinoma, plus a Phase 1/2 study in KRAS G12D-mutated solid tumors. VS-7375 is investigational and has not been approved by the FDA.
VS-7375 is being studied in four recruiting trials: NCT07659795 in KRAS G12D-mutated colorectal cancer, NCT07659782 in KRAS G12D-mutated non-small cell lung cancer, NCT07644559 in KRAS G12D-mutated pancreatic cancer, and NCT07020221, a Phase 1/2 study in KRAS G12D-mutated solid tumors. All enroll adults aged 18 and older.
The VS-7375 trials are recruiting at sites in the United States and Australia, with additional sites in Canada, Puerto Rico, France, and Spain. The colorectal cancer study enrolls in the United States and Australia, while the pancreatic cancer and Phase 1/2 solid tumor studies include the broader set of countries.