Low Grade Serous Ovarian Cancer, Ovarian Cancer
Conditions
Keywords
KRAS, KRAS wt, KRAS mt
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.
Interventions
combination therapy
Sponsors
Japanese Gynecologic Oncology Group
Verastem, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
| 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 |
Countries
Japan
Outcome results
None listed