Study of Avutometinib (VS-6766) + Adagrasib in KRAS G12C NSCLC Patients (RAMP204)

Verastem

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Metastatic Cancer; Advanced Cancer; Malignant Neoplastic Disease; KRAS Activating Mutation; Malignant Neoplasm of Lung; Non Small Cell Lung Cancer

Treatments: Drug: avutometinib (VS-6766) and adagrasib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05375994

VS-6766-204

Details and patient eligibility

About

This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with adagrasib in patients with G12C Non-Small Cell Lung Cancer (NSCLC) who have been exposed to prior G12C inhibitor and experienced progressive disease.

Full description

This is a multicenter, non-randomized, open-label Phase 1/2 study designed to evaluate safety, tolerability and efficacy of avutometinib (VS-6766) in combination with adagrasib in patients with KRAS G12C mutant NSCLC who have been exposed to prior G12C inhibitor and experienced progressive disease.

Enrollment: 85 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female subjects ≥ 18 years of age
• Histologic or cytologic evidence of NSCLC
• Known KRAS G12C mutation
• The subject must have received prior therapy with a KRAS G12C inhibitor and experienced progression
• Must have received appropriate treatment with at least one prior systemic regimen, but no more than 3 prior regimens, for Stage 3B-C or 4 NSCLC
• Measurable disease according to RECIST 1.1
• An Eastern Cooperative Group (ECOG) performance status ≤ 1
• Adequate organ function
• Adequate recovery from toxicities related to prior treatments
• Agreement to use highly effective method of contraceptive

Exclusion criteria

• Prior chemotherapy, targeted therapies, radiotherapy, immunotherapy or treatment with an investigational agent within 14 days of receipt of study drug (within 6 weeks for nitrosoureas, mitomycin C and chest radiation; within 6 months prior to Cycle 1 Day 1 for chest radiation > 30Gy)
• History of prior malignancy, with the exception of curatively treated malignancies
• Major surgery within 4 weeks (excluding placement of vascular access)
• Exposure to strong CYP3A4 inhibitors or inducers within 14 days prior to the first dose and during the course of therapy
• Exposure to strong inhibitors of breast cancer resistance protein (BCRP) within 14 days prior to the first dose and during the course of therapy
• Symptomatic brain metastases requiring steroids or other local interventions within the 2 weeks prior to initiation of therapy
• Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy
• Known hepatitis B, hepatitis C, or human immunodeficiency virus infection that is active
• Active skin disorder that has required systemic therapy within the past 1 year
• History of rhabdomyolysis or interstitial lung disease
• Concurrent ocular disorders
• Concurrent heart disease or severe obstructive pulmonary disease
• Subjects with the inability to swallow oral medications

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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85 participants in 2 patient groups

avutometinib(VS-6766)+adagrasib

Experimental group

Description:

To determine the recommended phase 2 dose (RP2D) for VS-6766 in combination with adagrasib in G12C inhibitor exposed patients

Treatment:

Drug: avutometinib (VS-6766) and adagrasib

avutometinib (VS-6766)+adagrasib RP2D

Experimental group

Description:

To determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients

Treatment:

Drug: avutometinib (VS-6766) and adagrasib