A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer
Gynecologic Cancers
Ovarian Cancer
Primary Peritoneal Cancer
18 Years and older, Female
VS-6766-301 (primary)
NCI-2024-00300
ENGOT-ov81
GOG-3097
Summary
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.
Objectives
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)
Eligibility
- 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.
Treatment Sites in Georgia
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