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 Genders
- 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. Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease. 3. Measurable disease according to RECIST v1.1. 4. An Eastern Cooperative Group (ECOG) performance status ≤ 1. 5. Adequate organ function 6. Adequate recovery from toxicities related to prior treatments. 7. For patients with reproductive potential, Agreement to use highly effective method of contraceptive. 8. 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 ovarian cancer or another 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. 6. Symptomatic brain metastases or spinal cord compression. 7. An active skin disorder that has required systemic therapy within one year of signing informed consent. 8. History of medically significant rhabdomyolysis. 9. For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor. 10. Symptomatic bowel obstruction within 3 months. 11. Concurrent ocular disorders. 12. Concurrent heart disease or severe obstructive pulmonary disease. 13. Subjects with the inability to swallow oral medications. 14. 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 (eg, Monday/Thursday, Tuesday/Friday, or Wednesday/Saturday) 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. - Topotecan: 4 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
San Francisco, California 94143
Miami Beach, Florida 33140
Orlando, Florida 32804
West Palm Beach, Florida 33401
Atlanta, Georgia 30322
Evanston, Illinois 60201
Baltimore, Maryland 21287
Minneapolis, Minnesota 55404
Saint Louis, Missouri 63110
New York, New York 10065
Rachel Grisham
646-888-4653
Oklahoma City, Oklahoma 73104
Eugene, Oregon 97401
Portland, Oregon 97227
Philadelphia, Pennsylvania 19090
Pittsburgh, Pennsylvania 15224
Fort Worth, Texas 76104
The Woodlands, Texas 77380
Charlottesville, Virginia 22908
Gainesville, Virginia 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 a type of drug called a kinase inhibitor. 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 five 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 standard 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)