A Study of Avutometinib (VS-6766) V. Avutometinib (VS-6766) + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer with and Without a KRAS Mutation
- Conditions
- Low Grade Ovarian Serous AdenocarcinomaOvarian Cancer
- Interventions
- Registration Number
- NCT04625270
- Lead Sponsor
- Verastem, Inc.
- Brief Summary
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)
- Detailed 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 225
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part B avutometinib (VS-6766) and defactinib To determine the efficacy of the optimal regimen identified from Part A Part A avutometinib (VS-6766) and defactinib 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) Part A avutometinib (VS-6766) 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) Part B avutometinib (VS-6766) To determine the efficacy of the optimal regimen identified from Part A Part C: avutometinib (VS-6766) and defactinib To evaluate additional efficacy parameters for the optimal regimen identified in Part A. Part D avutometinib (VS-6766) and defactinib To evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib
- Primary Outcome Measures
Name Time Method Part A: Determine optimal regimen of avutometinib (VS-6766) monotherapy or in combination with defactinib From start of treatment to confirmation of response; 24 weeks Confirmed overall response rate per RECIST 1.1
Part B: To determine the efficacy of the optimal regimen identified from Part A From start of treatment to confirmation of response; 24 weeks Confirmed overall response rate per RECIST 1.1
Part C: To evaluate additional efficacy parameters for the optimal regimen identified in Part A From start of treatment to confirmation of response; 24 weeks Confirmed overall response rate per RECIST 1.1
Part D:To evaluate additional efficacy parameters for a lower dose of avutometinib in combination with defactinib From start of treatment to confirmation of response; 24 weeks Confirmed ORR defined according to RECIST 1.1
- Secondary Outcome Measures
Name Time Method Overall Response Rate as assessed by Investigator From start of treatment to confirmation of response; 24 weeks Proportioned subjects achieving a CR or PR as assess by the investigator
Disease Control Rate (DCR) Greater than or equal to 8 weeks CR+PR+stable disease
Overall Survival (OS) Up to 5 years From time of first dose of study intervention to death
Duration of Response (DOR) Time from the first documentation of response to first documentation of progressive disease or death due to any cause, greater than or equal to 6 months From time of first response to PD as assessed by the BIRC
Progression Free Survival (PFS) Up to 5 years From time of first dose of study intervention to PD or death for any cause
Trial Locations
- Locations (44)
Arizona Oncology Associates PC HAL
🇺🇸Scottsdale, Arizona, United States
Sansum Clinic
🇺🇸Santa Barbara, California, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Advent Health
🇺🇸Orlando, Florida, United States
H. Lee Moffitt Cancer Center and Research Institute - Center for Women's Oncology
🇺🇸Tampa, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Maryland Oncology and Hematology, P.A.
🇺🇸Glenn Dale, Maryland, United States
Minnesota Oncology Hematology PA
🇺🇸Minneapolis, Minnesota, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Scroll for more (34 remaining)Arizona Oncology Associates PC HAL🇺🇸Scottsdale, Arizona, United States