Clinical trial NCT06682572: A Study of Avutometinib + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer in Japanese Patients
Official title: A Phase 2 Study of Avutometinib (VS-6766, a Dual RAF/MEK Inhibitor) In Combination With Defactinib (FAK Inhibitor) in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) in Japanese Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Low Grade Serous Ovarian Cancer
Ovarian Cancer
Keywords: KRAS
KRAS wt
KRAS mt
Lead sponsor: Verastem, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Japanese Gynecologic Oncology Group
First posted: 2024-11-12
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

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, 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

Primary outcomes:
measure: Confirmed overall response rate (ORR; partial response [PR] + complete response [CR]
timeFrame: From start of treatment to confirmation of response; 24 weeks
Secondary outcomes:
measure: Duration of Response
timeFrame: 12 months
measure: Objective response rate (ORR)
timeFrame: 12 months
measure: Progression free survival (PFS)
timeFrame: 24 months
measure: Disease control rate (DCR)
timeFrame: 6 months
measure: Clinical benefit rate
timeFrame: 6 months
measure: Overall Survival (OS)
timeFrame: up to 2 years
measure: Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 18 months
measure: Area under the plasma concentration-time curve (AUC) of avutometinib, defactinib and relative metabolites
timeFrame: 9 months
measure: Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites
timeFrame: 9 months
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Tsu
country: Japan
facility: Mie University Hospital
state: Mie
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Minato City
country: Japan
facility: Jikei University Hospital
state: Tokyo
Study officials:
References: