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.
Eligibility
Sex
FEMALE
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
Patients may be eligible for inclusion in the study if they meet the following criteria:
1. Histologically proven LGSOC (ovarian, fallopian, peritoneal)
2. Documented mutational status of KRAS by a validated tumor-tissue based diagnostic test.
3. Suitable for treatment with at least one of the Investigator's Choice of Treatments:pegylated liposomal doxorubicin, paclitaxel, letrozole, anastrozole.
4. Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
5. Measurable disease according to RECIST v1.1.
6. An Eastern Cooperative Group (ECOG) performance status ≤ 1.
7. Adequate organ function.
8. Adequate recovery from toxicities related to prior treatments.
9. For patients with reproductive potential, a negative pregnancy test must be confirmed and agreement to use highly effective method of contraceptive.
10. Willingness to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
Exclusion Criteria:
Patients will be excluded from the study if they meet any of the following criteria:
1. Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
2. Co-existing high-grade serous ovarian cancer or mixed histology.
3. Prior treatment with avutometinib, defactinib, or other FAK inhibitors.
4. History of prior malignancy with recurrence \<3 years from the time of enrollment.
5. Major surgery within 4 weeks, minor surgery within 1 week, or palliative radiotherapy within 1 week of the first dose of study intervention.
6. Symptomatic brain metastases requiring steroids or other interventions, known leptomeningeal metastases, or spinal cord compression.
7. An active skin disorder that has required systemic therapy within one year of the first dose of study intervention.
8. History of medically significant rhabdomyolysis.
9. For subjects with prior MEK or RAF exposure, Grade 4 toxicity is deemed related to the MEK inhibitor.
10. Symptomatic bowel obstruction within 3 months of the first dose of study intervention
11. Concurrent ocular disorders.
12. Concurrent heart disease or severe obstructive pulmonary disease.
13. Active or past medical history of interstitial lung disease/pneumonitis, including drug-induced or radiation pneumonitis, pulmonary fibrosis, or adult respiratory distress syndrome (ARDS).
14. Subjects with the inability to swallow oral medications.
15. History of hypersensitivity to any of the active agents or ingredients of study intervention: peanut, soya, polyoxyl castor oil, etcetc.). Prior hypersensitivity to anthracyclines or anthracenediones if the use of pegylated liposomal doxorubicin (PLD) is planned.
16. Pregnant or breastfeeding.
17. Active, uncontrolled infection (bacterial, viral, or fungal) requiring systemic therapy.
Primary outcome measure(s)
Progression Free Survival (PFS) per blinded independent central review (BICR) — Up to 24 months Progression-free survival (PFS) according to RECIST version 1.1, per blinded independent central review (BICR)
Trial sites (106)
Facility
City
Region
Status
HonorHealth
Phoenix
Arizona
Recruiting
University of Arkansas
Little Rock
Arkansas
Recruiting
UCLA Health
Los Angeles
California
Recruiting
UC Davis
Sacramento
California
Recruiting
University of California, San Francisco
San Francisco
California
Active Not Recruiting
Yale University
New Haven
Connecticut
Recruiting
Florida Cancer Specialists - South
Fort Myers
Florida
Recruiting
Mount Sinai
Miami Beach
Florida
Recruiting
AdventHealth
Orlando
Florida
Recruiting
Moffitt Cancer Center
Tampa
Florida
Recruiting
Florida Cancer Specialists Research East
West Palm Beach
Florida
Recruiting
Winship Cancer Institute at Emory University
Atlanta
Georgia
Recruiting
NorthShore University HealthSystem
Evanston
Illinois
Recruiting
Louisiana State University
New Orleans
Louisiana
Recruiting
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore
Maryland
Recruiting
Karmanos Cancer Center
Detroit
Michigan
Recruiting
Minnesota Oncology Hematology
Minneapolis
Minnesota
Recruiting
Washington University School of Medicine
St Louis
Missouri
Recruiting
Roswell Park Cancer Institute
Buffalo
New York
Active Not Recruiting
Memorial Sloan Kettering Cancer Center
New York
New York
Recruiting
Atrium Health
Charlotte
North Carolina
Recruiting
Cleveland Clinic Foundation
Cleveland
Ohio
Recruiting
Ohio State
Hilliard
Ohio
Recruiting
University of Oklahoma Medical Center
Oklahoma City
Oklahoma
Recruiting
Willamette Valley Cancer Institute
Eugene
Oregon
Recruiting
Northwest Cancer Specialists
Portland
Oregon
Recruiting
Asplundh Cancer Pavilion | Jefferson Health
Philadelphia
Pennsylvania
Recruiting
Allegheny Health Network
Pittsburgh
Pennsylvania
Recruiting
Texas Oncology Central
Austin
Texas
Recruiting
Texas Oncology-Fort Worth Cancer Center
Fort Worth
Texas
Recruiting
Houston Methodist
Houston
Texas
Recruiting
MD Anderson Cancer Center
Houston
Texas
Recruiting
Texas Oncology
San Antonio
Texas
Recruiting
Texas Oncology
The Woodlands
Texas
Recruiting
Texas Oncology
Tyler
Texas
Recruiting
Intermountain Medical Center
Murray
Utah
Recruiting
University of Virginia Health System
Charlottesville
Virginia
Recruiting
Virginia Cancer Specialists, PC
Gainesville
Virginia
Recruiting
Prince of Wales Hospital
Randwick
New South Wales
Recruiting
Icon Cancer Centre Wesley
Auchenflower
Queensland
Recruiting
+ 66 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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