Clinical trials

The purpose of this study is to learn whether the study drugs avutometinib and defactinib can help stop or shrink malignant peripheral nerve sheath tumors (MPNST) that have returned or cannot be removed with surgery.

Based on the clinical activity of both selumetinib and cabozantinib as monotherapies in clinical trials, the demonstrated activity of these agents in reduced doses in preclinical studies, and the non-overlapping toxicity profiles, the study will assess the tolerability and efficacy of selumetinib and cabozantinib in combination in participants with NF1 ≥16 years old with progressive and/or symptomatic PN in a phase 1/1b/2 clinical trial. Trial Design Phase 1 This will be an open label, dose escalation phase. Dose level escalation will be determined by a rolling six design. In this design, up to 6 participants can be enrolled at a given dose level and then evaluated for dose limiting toxicity (DLT) within the DLT window. The DLT window is defined as 16 weeks in this study based on the long half-life of cabozantinib and the desire to have maximum confidence about long-term tolerability of the combination prior to proceeding to the next dose level. Phase 1b Once the recommended phase 2 dose has been determined in phase 1, an expanded cohort of 12 participants will be enrolled in phase 1b portion of the study. Phase 2 This will be an open label, single-arm phase using the recommended phase 2 dose.