Study of Cabozantinib With Selumetinib for Plexiform Neurofibromas

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.

NCT Number	NCT06502171
Lead Sponsor	Girish Dhall, MD Collaborators: Children's Hospital of Philadelphia, Indiana University, United States Department of Defense
Conditions	Neurofibromatosis 1, Plexiform Neurofibroma
Enrollment	30 participants
Start Date	2026-08-01
Primary Completion	2033-08-01 (estimated)
Study Completion	2034-08-01 (estimated)
Updated on ClinicalTrials.gov	2026-03-12