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

Verastem

Status and phase: Not yet enrolling; Phase 2; Phase 1

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

Treatments: Drug: Cetuximab; Drug: VS-7375

Study type: Interventional

Funder types: Industry

Identifiers

NCT07020221

VS-7375-101

Details and patient eligibility

About

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.

Enrollment: 130 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 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

Key Exclusion Criteria:

• Underwent major surgical procedure as defined by the Investigator, other than for diagnosis, within 4 weeks prior to Cycle 1 Day 1,
• Receipt of chemotherapy, targeted therapy, or radiotherapy (excluding palliative radiation) within 4 weeks or 5 half-lives, whichever is shorter, or immunotherapy within 4 weeks prior to Cycle 1 Day 1
• Treatment with any investigational drug at least 4 weeks or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1.
• History of treatment with direct and specific KRAS G12D inhibitors.
• Symptomatic, untreated, or actively progressing known central nervous system (CNS) metastases.
• Inability to swallow oral medications.
• Evidence or history of uncontrolled, clinically significant hematological, renal, hepatic, endocrine, pulmonary, gastrointestinal, cardiovascular, psychiatric, coagulation, neurologic, dermatologic, autoimmune, or allergic disease
• Individuals who are pregnant or breastfeeding.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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130 participants in 4 patient groups

VS-7375 Dose Escalation

Experimental group

Description:

To determine the recommended phase 2 dose (RP2D) for VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation.

Treatment:

Drug: VS-7375

Cetuximab + VS-7375 Dose Escalation

Experimental group

Description:

To determine the recommended phase 2 dose (RP2D) for cetuximab + VS-7375 in patients with advanced solid tumors harboring a KRAS G12D mutation.

Treatment:

Drug: VS-7375

Drug: Cetuximab

VS-7375 Recommended Phase 2 Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: VS-7375

Cetuximab + VS-7375 Recommended Phase 2 Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: VS-7375

Drug: Cetuximab