This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with defactinib versus Investigator's choice of treatments (ICT) in subjects with recurrent LGSOC who have progressed on a prior platinum-based therapy.
This international, randomized, open-label, Phase 3 study will compare the investigational combination of avutometinib plus defactinib versus Investigator's Choice of Treatments (ICT) in patients with recurrent LGSOC who have progressed on a prior platinum-based therapy. Avutometinib and defactinib are both types of drugs called kinase inhibitors. Kinase inhibitors block cancer cell growth. The study will compare the progression-free survival (PFS) of the combination of avutometinib plus defactinib versus ICT. The study will also evaluate the effect of the combination on safety, overall survival, other efficacy endpoints, and health-related quality of life and disease related symptoms. The study is being conducted by gynecological cancer specialists. Patients who are eligible and agree to participate in this study will be treated with either a combination of avutometinib with defactinib, or with one of four standard of care NCCN and ESMO treatment recommendations for recurrent LGSOC, and then with subsequent follow up appointments. Patients who originally received one of the standards of care treatments who are determined to have progressive disease may be eligible to crossover to receive the investigational combination avutometinib plus defactinib.Avutometinib and defactinib are investigational drugs that have not been approved by the U.S. Food and Drug Administration (FDA)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
270
Avutometinib: administered orally
Defactinib: administered orally
administered intravenously
Progression Free Survival (PFS) per blinded independent central review (BICR)
Progression-free survival (PFS) according to RECIST version 1.1, per blinded independent central review (BICR)
Time frame: Up to 24 months
Overall Survival (OS)
From the time of first dose of study intervention to PD as assessed per RECIST 1.1 or death from any cause
Time frame: Up to 5 years
Progression Free Survival (PFS) per investigator assessment
Progression-free survival (PFS) according to RECIST version 1.1, per blinded independent central review (BICR)
Time frame: 24 months
Objective response rate (ORR)
From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
Time frame: 12 months
Duration of Response (DOR)
From the time of first dose of study intervention to PD as assessed per RECIST 1.1 by Investigator or death from any cause
Time frame: 12 months
Disease Control Rate (DCR)
CR+PR+Stable disease
Time frame: 6 months
Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)
Count of AE and SAEs by grade, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale
Time frame: 25 months
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administered intravenously
administered orally
administered orally
HonorHealth
Phoenix, Arizona, United States
RECRUITINGUniversity of Arkansas
Little Rock, Arkansas, United States
RECRUITINGUCLA Health
Los Angeles, California, United States
RECRUITINGUC Davis
Sacramento, California, United States
RECRUITINGUniversity of California, San Francisco
San Francisco, California, United States
RECRUITINGYale University
New Haven, Connecticut, United States
RECRUITINGFlorida Cancer Specialists - South
Fort Myers, Florida, United States
RECRUITINGMount Sinai
Miami Beach, Florida, United States
RECRUITINGAdventHealth
Orlando, Florida, United States
RECRUITINGMoffitt Cancer Center
Tampa, Florida, United States
RECRUITING...and 96 more locations
Area under the plasma concentration-time curve (AUC) of avutometinib, defactinib and relative metabolites
Area under plasma Concentration (AUC) 0 to t
Time frame: 5 months
Maximum plasma concentration (Cmax) of avutometinib, defactinib and relative metabolites
maximum plasma concentration
Time frame: 5 months
To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Core module C30 (QLQ-C30).
The EORTC QLQ-C30 is a validated questionnaire to assess the quality of life of ovarian cancer patients.
Time frame: 24 months
To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Ovarian Cancer module OV28 (QLQ-OV28).
The EORTC QLQ-OV28 is a validated questionnaire to assess the quality of life of ovarian cancer patients.
Time frame: 24 months
To assess the health-related quality of life and disease based on EuroQol-5 Dimension 5-level (EQ-5D-5L)
The EuroQol-5 Dimension 5-level (EQ-5D-5L) is a validated questionnaire used to measure a patient's overall health.
Time frame: 24 months