Low Grade Ovarian Serous Adenocarcinoma, Ovarian Cancer
Conditions
Keywords
Low Grade Serous Ovarian Cancer, KRAS, KRAS wt
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.
Interventions
avutometinib (VS-6766) monotherapy
avutometinib (VS-6766) and defactinib combination
Sponsors
European Network of Gynaecological Oncological Trial Groups (ENGOT)
GOG Foundation
Verastem, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Disease Control Rate (DCR) | Greater than or equal to 8 weeks | CR+PR+stable disease |
| Progression Free Survival (PFS) | Up to 5 years | From time of first dose of study intervention to PD or death for any cause |
Countries
Belgium, Canada, France, Italy, Spain, United Kingdom, United States
Outcome results
None listed