A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer
Purpose
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.
Condition
- Low Grade Serous Ovarian Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- Female
- Accepts 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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental avutometinib + defactinib |
Avutometinib 3.2 mg, 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. |
|
|
Active Comparator Investigator Choice of Treatment (ICT) |
Patients will receive one of the following therapies as determined by the Investigator: - Pegylated liposomal doxorubicin: 40 mg/m2 IV on Day 1 of each 28-day (4 week) cycle. - Paclitaxel: 80 mg/m2 IV on Days 1, 8, and 15 of each 28-day (4 week) cycle. - Anastrozole: 1 mg, PO, once daily of each 28-day (4 week) cycle. - Letrozole: 2.5 mg, PO, once daily of each 28-day (4 week) cycle. |
|
Recruiting Locations
Little Rock 4119403, Arkansas 4099753 72205
Los Angeles 5368361, California 5332921 90095
San Francisco 5391959, California 5332921 94143
New Haven 4839366, Connecticut 4831725 06520
Fort Myers 4155995, Florida 4155751 33901
Miami Beach 4164143, Florida 4155751 33140
Orlando 4167147, Florida 4155751 32804
Tampa 4174757, Florida 4155751 33612
West Palm Beach 4177887, Florida 4155751 33401
Atlanta 4180439, Georgia 4197000 30322
Evanston 4891382, Illinois 4896861 60201
New Orleans 4335045, Louisiana 4331987 70112
Baltimore 4347778, Maryland 4361885 21287
Detroit 4990729, Michigan 5001836 48201
Minneapolis 5037649, Minnesota 5037779 55404
St Louis 4407066, Missouri 4398678 63110
Buffalo 5110629, New York 5128638 14263
New York 5128581, New York 5128638 10065
Rachel Grisham
646-888-4653
Charlotte 4460243, North Carolina 4482348 28203
Cleveland 5150529, Ohio 5165418 44195
Oklahoma City 4544349, Oklahoma 4544379 73104
Eugene 5725846, Oregon 5744337 97401
Portland 5746545, Oregon 5744337 97227
Philadelphia 4560349, Pennsylvania 6254927 19090
Pittsburgh 5206379, Pennsylvania 6254927 15224
Austin 4671654, Texas 4736286 78731
Fort Worth 4691930, Texas 4736286 76104
Houston 4699066, Texas 4736286 77030
Houston 4699066, Texas 4736286 77030
San Antonio 4726206, Texas 4736286 78229
The Woodlands 4736476, Texas 4736286 77380
Tyler 4738214, Texas 4736286 75702
Murray 5778755, Utah 5549030 84107
Charlottesville 4752031, Virginia 6254928 22908
Gainesville 4760363, Virginia 6254928 20155
More Details
- NCT ID
- NCT06072781
- Status
- Recruiting
- Sponsor
- Verastem, Inc.
Detailed Description
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)