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 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)
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. 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.
Treatment Sites in Georgia
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