A Study of Avutometinib (VS-6766) v. Avutometinib (VS-6766) + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer With and Without a KRAS Mutation

Inclusion Criteria:

Histologically proven LGSOC (ovarian, peritoneal)
In Part A KRAS mutation, KRAS wt
Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
Measurable disease according to RECIST 1.1
An Eastern Cooperative Group (ECOG) performance status ≤ 1.
Adequate organ function
Adequate recovery from toxicities related to prior treatments
Agreement to use highly effective method of contraceptive

Exclusion Criteria:

Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy
Co-existing high-grade ovarian cancer or another histology
History of prior malignancy with recurrence <3 years from the time of enrollment
Major surgery within 4 weeks
Symptomatic brain metastases requiring steroids or other interventions
Known SARS-Cov2 infection (clinical symptoms) ≤28 days prior to first dose of study therapy
For subjects with prior MEK exposure, Grade 4 toxicity deemed related to the MEK inhibitor
Active skin disorder that has required systemic therapy within the past year
History of rhabdomyolysis
Concurrent ocular disorders
Concurrent heart disease or severe obstructive pulmonary disease
Subjects with the inability to swallow oral medications