A Phase 1/2a, 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

Status: Recruiting
Location: See all (5) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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.

• Must have received ≥1 prior line of standard systemic therapy for advanced or metastatic disease or experienced cancer progression within 6 months of neoadjuvant or adjuvant therapy.

• 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

Locations
United States
Massachusetts
Massachusetts General Hospital
RECRUITING
Boston
Missouri
Washington University School of Medicine
RECRUITING
St Louis
Tennessee
SCRI Oncology Partners
RECRUITING
Nashville
Texas
MD Anderson Cancer Center
RECRUITING
Houston
Washington
Virginia Mason Medical Center
RECRUITING
Seattle
Contact Information
Primary
Verastem Call Center
clinicaltrials@verastem.com
1 781 292 4204
Time Frame
Start Date: 2025-06-24
Estimated Completion Date: 2028-09
Participants
Target number of participants: 330
Treatments
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 and NSCLC 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.
Sponsors
Leads: Verastem, Inc.

This content was sourced from clinicaltrials.gov