A Study of Avutometinib (VS-6766) + Defactinib in Recurrent KRAS G12V, Other KRAS and BRAF Non-Small Cell Lung Cancer (RAMP202)

Verastem

Status and phase: Completed; Phase 2

Conditions: KRAS Activating Mutation; Non Small Cell Lung Cancer

Treatments: Drug: avutometinib (VS-6766); Drug: avutometinib (VS-6766) and Defactinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04620330

VS-6766-202

Details and patient eligibility

About

This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy or VS-6766 in combination with defactinib in subjects with recurrent Non-small cell lung cancer.

Full description

This is a multicenter, open-label Phase 2 study designed to evaluate safety and tolerability and efficacy of avutometinib (VS-6766) versus avutometinib (VS-6766) in combination with defactinib in subjects with KRAS and BRAF mutant NSCLC following treatment with an appropriate platinum-based regimen and an approved immune checkpoint inhibitor (CPI).

Enrollment: 90 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 or BRAF mutation
• The subject must have received appropriate prior therapy
• 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

• Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
• History of prior malignancy, with the exception of curatively treated malignancies
• Major surgery within 4 weeks (excluding placement of vascular access)
• History of treatment with a direct and specific inhibitor of MEK, KRAS or BRAF except for treatment of BRAF V-600E mutant NSCLC
• Exposure to strong CYP2C9 and CYP3A4 inhibitors or inducers within 7 days prior to the first dose and during the course of therapy
• Symptomatic brain metastases requiring steroids or other local interventions.
• Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy
• Active skin disorder that has required systemic therapy within the past 1 year
• History of rhabdomyolysis
• 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: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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90 participants in 5 patient groups

Arm 1: avutometinib (VS-6766) monotherapy

Experimental group

Description:

in patients with NSCLC KRAS-G12V tumor

Treatment:

Drug: avutometinib (VS-6766)

Arm 2: avutometinib (VS-6766) in combination with defactinib

Experimental group

Description:

in patients with a NSCLC KRAS-G12V tumor

Treatment:

Drug: avutometinib (VS-6766) and Defactinib

Arm 3: avutometinib (VS-6766) in combination with defactinib

Experimental group

Description:

in patients with a NSCLC KRAS-other (non-G12V) tumor

Treatment:

Drug: avutometinib (VS-6766) and Defactinib

Arm 4: avutometinib (VS-6766) in combination with defactinib

Experimental group

Description:

in patients with a NSCLC BRAF-V600E tumor

Treatment:

Drug: avutometinib (VS-6766) and Defactinib

Arm 5:avutometinib (VS-6766) in combination with defactinib

Experimental group

Description:

in patients with a NSCLC BRAF-non-V600E tumor

Treatment:

Drug: avutometinib (VS-6766) and Defactinib