Status:

RECRUITING

A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer

Lead Sponsor:

Verastem, Inc.

Collaborating Sponsors:

GOG Foundation

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Conditions:

Low Grade Serous Ovarian Cancer

Eligibility:

FEMALE

18+ years

Phase:

PHASE3

Brief 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 progr...

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...

Eligibility Criteria

Inclusion

  • Patients may be eligible for inclusion in the study if they meet the following criteria:
  • Histologically proven LGSOC (ovarian, fallopian, peritoneal)
  • Documented mutational status of KRAS by a validated tumor-tissue based diagnostic test.
  • Suitable for treatment with at least one of the Investigator's Choice of Treatments:pegylated liposomal doxorubicin, paclitaxel, letrozole, anastrozole.
  • Progression or recurrence of LGSOC after at least one prior systemic therapy for metastatic disease.
  • Measurable disease according to RECIST v1.1.
  • An Eastern Cooperative Group (ECOG) performance status ≤ 1.
  • Adequate organ function.
  • Adequate recovery from toxicities related to prior treatments.
  • For patients with reproductive potential, a negative pregnancy test must be confirmed and agreement to use highly effective method of contraceptive.
  • Willingness to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion

  • Patients will be excluded from the study if they meet any of the following criteria:
  • Systemic anti-cancer therapy within 4 weeks of the first dose of study therapy.
  • Co-existing high-grade serous ovarian cancer or mixed histology.
  • Prior treatment with avutometinib, defactinib, or other FAK inhibitors.
  • History of prior malignancy with recurrence \<3 years from the time of enrollment.
  • Major surgery within 4 weeks, minor surgery within 1 week, or palliative radiotherapy within 1 week of the first dose of study intervention.
  • Symptomatic brain metastases requiring steroids or other interventions, known leptomeningeal metastases, or spinal cord compression.
  • An active skin disorder that has required systemic therapy within one year of the first dose of study intervention.
  • History of medically significant rhabdomyolysis.
  • For subjects with prior MEK or RAF exposure, Grade 4 toxicity is deemed related to the MEK inhibitor.
  • Symptomatic bowel obstruction within 3 months of the first dose of study intervention
  • Concurrent ocular disorders.
  • Concurrent heart disease or severe obstructive pulmonary disease.
  • Active or past medical history of interstitial lung disease/pneumonitis, including drug-induced or radiation pneumonitis, pulmonary fibrosis, or adult respiratory distress syndrome (ARDS).
  • Subjects with the inability to swallow oral medications.
  • 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.
  • Pregnant or breastfeeding.
  • Active, uncontrolled infection (bacterial, viral, or fungal) requiring systemic therapy.

Key Trial Info

Start Date :

March 18 2024

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

February 9 2031

Estimated Enrollment :

270 Patients enrolled

Trial Details

Trial ID

NCT06072781

Start Date

March 18 2024

End Date

February 9 2031

Last Update

November 14 2025

Active Locations (105)

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Page 1 of 27 (105 locations)

1

HonorHealth

Phoenix, Arizona, United States, 85016

2

University of Arkansas

Little Rock, Arkansas, United States, 72205

3

UCLA Health

Los Angeles, California, United States, 90095

4

UC Davis

Sacramento, California, United States, 95817