CTIM-22. WINDOW OF OPPORTUNITY STUDY OF NIVOLUMAB AND IPILIMUMAB IN PEOPLE WITH NEUROFIBROMATOSIS TYPE 1 AND NEWLY DIAGNOSED MALIGNANT AND PRE-MALIGNANT PERIPHERAL NERVE SHEATH TUMORS

Abstract Neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas with no curative medical therapies. Most clinical trials target recurrent or refractory disease, leaving a critical gap in early-stage treatment strategies. Given the immunogenic potential of MPNST and the need for innovative trials for this rare and fatal peripheral nervous system cancer, we conducted a multi-center study to assess the safety and feasibility of initiating neoadjuvant immunotherapy with nivolumab and ipilimumab immediately after diagnosis, prior to standard-of-care (SOC) therapy. Participants aged 12 years or older with NF1 and newly diagnosed atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP) or MPNST, planned for surgical resection, were enrolled across four sites. Within one week of diagnostic biopsy, patients received nivolumab (4.5 mg/kg IV) and ipilimumab (1 mg/kg IV) x two doses administered three weeks apart. This was followed by institution-specific SOC therapy (encompassing surgery, cytotoxic chemotherapy, radiation). Pharmacodynamic and immunologic biomarkers are being evaluated in serial blood samples and paired tumor samples for immune profiling including tumor-infiltrating lymphocytes and neoantigen-specific T cell clones. The primary endpoint was feasibility, defined by at least 60% of participants completing both doses and initiating SOC therapy within 8 weeks of biopsy tissue diagnosis. Of the 11 currently evaluable patients (1 ANNUBP, 10 MPNST, median age 35, 42% female), 10 met this benchmark (90%). Five participants continued nivolumab during SOC therapy. Adverse events were mostly mild (one dose-limiting toxicity) and often overlapped with expected SOC AE profiles. No participant discontinued treatment due to adverse events. Six patients (55%) experienced disease progression (PFS 4–12 months), and four have died (OS 9–31 months). These results demonstrate that early administration of nivolumab and ipilimumab is feasible and tolerable in people with NF1-associated MPNST and may provide a platform for future immune-based therapeutic strategies in this high-risk population.