Clinical Trial 23223

• Overview

  Study Title:

  A Phase 3, Randomized, Open-Label Study of Combination Therapy with Avutometinib plus Defactinib Versus Investigator s Choice of Treatment in Patients with Recurrent Low-Grade Serous Ovarian Cancer (LGSOC)

  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 Low-grade serous ovarian cancer (LGSOC) who have progressed on a prior platinum-based therapy.

  Objective:

  Primary Objective: * To compare the progression-free survival (PFS) of the combination of avutometinib plus defactinib vs Investigator s Choice of Treatment (ICT) in patients with recurrent LGSOC Secondary Objective: * To compare the combination of avutometinib plus defactinib vs ICT in patients with recurrent LGSOC with regard to additional efficacy parameters * To characterize the safety and tolerability of combination avutometinib plus defactinib vs ICT in patients with recurrent LGSOC * To determine the exposure of avutometinib and defactinib in patients with recurrent LGSOC treated with combination of avutometinib plus defactinib * To assess the health-related quality of life and disease related symptoms in patients with recurrent LGSOC treated with combination avutometinib plus defactinib vs ICT

• Treatments

  Therapies:

  Chemotherapy (NOS); Hormonal Therapy; Therapy (NOS)

  Medications:

  Anastrozole (); Arimadex (Anastrozole); Avutometinib (); Defactinib (VS-6063); Femara (Letrozole); Letrozole (); PEGylated Liposomal Doxorubicin (); Taxol (paclitaxel); Topotecan (); paclitaxel ()

• Inclusion Criteria

  Inclusion Criteria:
  • Histologically proven Low-grade serous ovarian cancer (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 of 1 or less.
  • 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 Criteria

  Exclusion 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 > 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.

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