Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT07020221 | A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors | PHASE1 | RECRUITING | 295 | — | — | Jun 24, 2025 | Dec 1, 2028 | Apr 22, 2026 | 14 | United States, Australia |
To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 administered on a daily oral schedule in participants with advanced solid tumors harboring a KRAS G12D mutation. Proportion/number of participants with AEs, TEAEs, TRAEs, SAEs, DLTs, and dose interruptions/reductions.
To identify the MTD or MFD using a BOIN design and recommend a dose for subsequent studies of VS-7375 on a daily oral schedule in participants with any KRAS G12D-mutated solid tumor. Proportion/number of participants with DLTs during the DLT assessment period (through C1D21).
To evaluate the preliminary anticancer activity of the optimal VS-7375 regimen identified from Part A in participants with advanced KRAS G12D-mutated PDAC (cohort B1), NSCLC (cohort B2), and other solid tumors (cohort B3). Confirmed ORR, PFS rate, unconfirmed PR and CR rates, DCR, DOR, and PFS per RECIST v1.1. Overall Survival
To characterize the safety, tolerability, and AE profile of VS-7375 in the following combination regimens in participants with any solid tumor harboring a KRAS G12D mutation. * 2L+ therapy in combination with cetuximab in participants with any advanced or metastatic solid tumor harboring a KRAS G12D mutation * 1L therapy in combination with carboplatin, pembrolizumab, and pemetrexed in participants with previously untreated metastatic NSCLC * 2L+ therapy in combination with gemcitabine and nab-paclitaxel in participants with metastatic PDAC * 1L therapy in combination with gemcitabine in participants aged 75 years or older with previously untreated metastatic PDAC. 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 preliminary anticancer activity of the optimal regimen of VS-7375 as identified in Part C as: * 2L+ therapy in combination with cetuximab in participants with metastatic colorectal adenocarcinoma * 1L therapy in combination with carboplatin, pembrolizumab, and pemetrexed in participants with previously untreated metastatic NSCLC * 2L+ therapy in combination with gemcitabine and nab-paclitaxel in participants with metastatic PDAC * 1L therapy in combination with gemcitabine in participants aged 75 years or older with previously untreated metastatic PDAC. Confirmed ORR, PFS rate, unconfirmed PR and CR rates, DCR, DOR, and PFS per RECIST v1.1. Overall survival
| Arm | Type | Description |
|---|---|---|
| VS-7375 Dose Escalation | EXPERIMENTAL | To determine the recommended phase 2 dose (RP2D) for VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation. |
| Cetuximab + VS-7375 Dose Escalation | EXPERIMENTAL | To determine the recommended phase 2 dose (RP2D) for cetuximab + VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation. |
| VS-7375 Recommended Phase 2 Dose Expansion | EXPERIMENTAL | To determine the efficacy of VS-7375 at the recommended phase 2 dose (RP2D) in patients with advanced PDAC, NSCLC, or solid tumors harboring a KRAS G12D mutation. |
| Cetuximab + VS-7375 Recommended Phase 2 Dose Expansion | EXPERIMENTAL | To determine the efficacy of cetuximab +VS-7375 at the recommended phase 2 dose (RP2D) in patients with advanced CRC harboring a KRAS G12D mutation. |
| VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Escalation | EXPERIMENTAL | To determine the recommended phase 2 dose (RP2D) for VS-7375 in combination with carboplatin/pemetrexed/pembrolizumab in patients with advanced 1L NSCLC harboring a KRAS G12D mutation. |
| VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Expansion | EXPERIMENTAL | To determine the efficacy of VS-7375 in combination with carboplatin/pemetrexed/pembrolizumab at the RP2D in patients with advanced 1L NSCLC harboring a KRAS G12D mutation. |
| VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Escalation | EXPERIMENTAL | To determine the recommended phase 2 dose (RP2D) for VS-7375 in combination with gemcitabine/nab-paclitaxel in patients with advanced PDAC harboring a KRAS G12D mutation. |
| VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Expansion | EXPERIMENTAL | To determine the efficacy of VS-7375 in combination with gemcitabine/nab-paclitaxel at the RP2D in patients with advanced PDAC harboring a KRAS G12D mutation. |
| VS-7375 + Gemcitabine Dose Escalation | EXPERIMENTAL | To determine the RP2D for VS-7375 in combination with gemcitabine in patients 75 years or older with advanced PDAC harboring a KRAS G12D mutation. |
| VS-7375 + Gemcitabine Dose Expansion | EXPERIMENTAL | The determine the efficacy of VS-7375 in combination with gemcitabine at the RP2D in patients 75 years or older with advanced PDAC harboring a KRAS G12D mutation. |
| Name | Type | Description |
|---|---|---|
| VS-7375 | DRUG | VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D (ON/OFF) inhibitor. |
| Cetuximab | DRUG | Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR). |
| Carboplatin + Pemetrexed + Pembrolizumab | DRUG | A combination therapy regimen used as a first-line treatment for advanced non-squamous non-small cell lung cancer. |
| Gemcitabine | DRUG | A chemotherapy used for the treatment of several types of cancer including advanced or metastatic pancreatic ductal adenocarcinoma. |
| Gemcitabine + Nab-paclitaxel | DRUG | A chemotherapy regimen used for the treatment of advanced or metastatic pancreatic ductal adenocarcinoma. |
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 harb...