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

First listed

Jun 13, 2025

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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