A Study of Avutometinib + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer in Japanese Patients
- Conditions
- Low Grade Serous Ovarian CancerOvarian Cancer
- Interventions
- Registration Number
- NCT06682572
- Lead Sponsor
- Verastem, Inc.
- Brief Summary
This study will confirm the safety and efficacy of avutometinib in combination with defactinib in Japanese patients with recurrent Low-Grade Serous Ovarian Cancer (LGSOC)
- Detailed Description
This is a multi-center, open label Phase 2 study designed to evaluate safety and tolerability and confirm efficacy by BICR of avutometinib in combination with defactinib in Japanese patients with molecularly profiled recurrent LGSOC.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 15
- Histologically proven LGSOC (ovarian, peritoneal)
- Documented mutational status of KRAS by validated diagnostic test of tumor tissue
- Documented disease progression (radiographic or clinical) or recurrence of LGSOC and have received at least one platinum-based chemotherapy agent
- 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, excluding ovarian cancer, 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
- Patients with the inability to swallow oral medications
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description avutometinib + defactinib Avutometinib (VS-6766) + Defactinib (VS-6063) Avutometinib 3.2mg, PO, twice weekly for 21 days on, 7 days off in a 28-day (4 weeks) cycle in combination with defactinib 200 mg, PO, twice daily for 21 days on, 7 days off in a 28-day (4 week) cycle.
- Primary Outcome Measures
Name Time Method Confirmed overall response rate (ORR; partial response [PR] + complete response [CR] From start of treatment to confirmation of response; 24 weeks Confirmed overall response rate (ORR; partial response \[PR\] + complete response \[CR\] defined according to Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]) as assessed by the blinded independent central radiology review committee (BICR)
- Secondary Outcome Measures
Name Time Method Duration of Response 12 months From the time of first dose of study intervention to PD as assessed by RECIST 1.1 or death from any cause
Objective response rate (ORR) 12 months From the time of first dose of study intervention to PD as assessed by RECIST 1.1 by Investigator or death from any cause.
Progression free survival (PFS) 24 months From the time of first dose of study intervention to first documentation of progressive disease (PD) or death by any cause
Disease control rate (DCR) 6 months CR + PR + SD
Clinical benefit rate 6 months CR + PR + (SD \>6 months)
Overall Survival (OS) up to 2 years From the time of first dose of study intervention to PD as assessed by RECIST 1.1 or death from any cause
Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) 18 months Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale
Area under the plasma concentration-time curve (AUC) of avutometinib, defactinib and relative metabolites 9 months Area under Plasma Concentration (AUC) 0 to t
Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites 9 months Maximum Plasma Concentration
Trial Locations
- Locations (5)
Aichi Cancer Center Hospital
🇯🇵Nagoya, Aichi, Japan
Kurume University Hospital
🇯🇵Kurume, Fukuoka, Japan
Mie University Hospital
🇯🇵Tsu, Mie, Japan
Tohoku University Hospital
🇯🇵Sendai, Miyagi, Japan
Jikei University Hospital
🇯🇵Minato City, Tokyo, Japan