A Phase 1/2 Study of VS-7375 in Patients With KRAS G12D-Mutated Solid Tumors

Conditions

• Colorectal Cancer
• G12D Mutated KRAS
• Non Small Cell Lung Cancer
• Pancreatic Ductal Adenocarcinoma
• Solid Tumor, Adult

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• 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.

Study Details

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.

Key Dates

Start date

Jun 24, 2025

Status verified

Apr 2026

Primary completion

Dec 31, 2028

Completion

Dec 31, 2028

Study Design

Enrollment

295 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: VS-7375 Dose Escalation
  To determine the recommended phase 2 dose (RP2D) for VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation.
• Experimental: Cetuximab + VS-7375 Dose Escalation
  To determine the recommended phase 2 dose (RP2D) for cetuximab + VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation.
• Experimental: VS-7375 Recommended Phase 2 Dose Expansion
  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.
• Experimental: Cetuximab + VS-7375 Recommended Phase 2 Dose Expansion
  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.
• Experimental: VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Escalation
  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.
• Experimental: VS-7375 + Carboplatin/Pemetrexed/Pembrolizumab Dose Expansion
  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.
• Experimental: VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Escalation
  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.
• Experimental: VS-7375 + Gemcitabine/Nab-Paclitaxel Dose Expansion
  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.
• Experimental: VS-7375 + Gemcitabine Dose Escalation
  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.
• Experimental: VS-7375 + Gemcitabine Dose Expansion
  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.

Primary Outcome Measure

Part A: To characterize the safety, tolerability, and AE profile of escalating doses of VS-7375 [ Time Frame: Up to 2.5 years ]

Central Contacts

• Verastem Call Center
  1 781 292 4204
  [email protected]

Locations (13)

Find similar trials in Los Angeles, CA

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