A Study of Avutometinib (VS-6766) v. Avutometinib (VS-6766) + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer With and Without a KRAS Mutation (RAMP 201)

Verastem

Status and phase: Active, not recruiting; Phase 2

Conditions: Low Grade Ovarian Serous Adenocarcinoma; Ovarian Cancer

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

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT04625270

ENGOT-ov60 (Other Identifier)

GOG-3052 (Other Identifier)

VS-6766-201

Details and patient eligibility

About

This study will assess the safety and efficacy of avutometinib (VS-6766) monotherapy and in combination with defactinib in subjects with recurrent Low-Grade Serous Ovarian Cancer (LGSOC)

Full description

This is a multicenter, randomized, open-label Phase 2 study designed to evaluate safety and tolerability and preliminary efficacy of avutometinib (VS-6766) versus avutometinib (VS-6766) in combination with defactinib in subjects with molecularly profiled recurrent LGSOC.

Enrollment: 225 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically proven LGSOC (ovarian, peritoneal)
• Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
• 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, if necessary

Exclusion criteria

• Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
• Co-existing high-grade ovarian cancer or another histology
• History of prior malignancy with recurrence <3 years from the time of enrollment
• Major surgery within 4 weeks
• Symptomatic brain metastases requiring steroids or other interventions
• Known SARS-Cov2 infection (clinical symptoms) ≤28 days prior to first dose of study therapy
• For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor
• Active skin disorder that has required systemic therapy within the past 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: Sequential Assignment

Masking: None (Open label)

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225 participants in 4 patient groups

Part A

Experimental group

Description:

To determine the optimal regimen, either avutometinib(VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, for subsequent evaluation for efficacy in the Expansion Phase (Part B)

Treatment:

Drug: avutometinib (VS-6766)

Drug: avutometinib (VS-6766) and defactinib

Part B

Experimental group

Description:

To determine the efficacy of the optimal regimen identified from Part A

Treatment:

Drug: avutometinib (VS-6766)

Drug: avutometinib (VS-6766) and defactinib

Part C:

Experimental group

Description:

To evaluate additional efficacy parameters for the optimal regimen identified in Part A.

Treatment:

Drug: avutometinib (VS-6766) and defactinib

Part D

Experimental group

Description:

To evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib

Treatment:

Drug: avutometinib (VS-6766) and defactinib