The purpose of this research is to test the effectiveness and safety of the study drugs (VS-6766 and defactinib), and see what effects (good and bad) these drugs have on the patients with endometrioid cancer, mucinous ovarian cancer, high-grade serous ovarian cancer, or solid gynecological cancer.
Female subjects ≥ 18 years of age.
Histologically proven gynecological cancers (endometrioid, MOC, HGSOC and solid gynecological cancers) with mutated RAS, BRAF (type I, II, and/or III), NF-1 loss of function, and/or RAS activation.
Mutational status will be taken from the previous next-gen sequencing (NGS) or molecular testing results and reviewed by the Principal Investigator prior to the start of treatment.
Adequate pathology material (as defined in the lab manual) must be available prior to treatment assignment to be used for confirmation.
Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
Prior MEKi or RAFi exposure.
Low grade serous ovarian cancer (LGSOC).
History of prior malignancy with recurrence <3 years from the time of enrollment. Subjects with basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, and in situ cervical cancer that has undergone potentially curative therapy with no evidence of disease recurrence for ≥1 year since completion of the appropriate therapy may be included. Subjects with other malignancies associated with very low risk of metastasis or death may be included upon discussion with the PI.
Single group
Avutometinib (VS-6766) + defactinib
DrugAvutometinib (VS-6766): will be administered at 3.2 mg orally twice a week Defactinib: will be administered at 200 mg orally twice a day (BID). Treatment will be for 3 weeks, followed by a 1-week rest period, in each 4-week (28 day) cycle.
Proportion of Patients with objective response rate
To evaluate the efficacy of Avutometinib (VS-6766) + defactinib in endometrioid, MOC, HGSOC and solid gynecological cancer patients with RAS/BRAF/NF1 mutations on confirmed overall response rate (ORR; partial response \[PR\] + complete response \[CR\] defined according to RECIST 1.1) as assessed by the investigator.
Incidence of Adverse Events
To characterize the safety and toxicity profile of Avutometinib (VS-6766) + defactinib combination measured by the incidence of Adverse events (AEs), serious AEs (SAEs), physical examinations, clinical laboratory values and tolerability (dose interruptions/reductions)
Duration of Response
Calculated for those subjects with a CR or PR as elapsed time from the first response to PD or death, as assessed by the investigator.
Progression Free Survival
elapsed time of first treatment to PD or death from any cause.
Disease Control Rate
CR+PR+ stable disease (SD) ≥8 weeks)
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University of Oklahoma
Lead sponsor
Verastem, Inc.
Collaborator
