A phase I/II study of nivolumab plus or minus ipilimumab in combination with multifraction stereotactic radiosurgery for recurrent high-grade radiation-relapsed meningioma.

Abstract

TPS2073 Background: There is currently lack of effective therapy for meningiomas that have relapsed despite surgery and radiation therapy (RT). Reirradiation have been used in selected cases, but the long-term clinical outcomes remained poor, especially for high-grade meningiomas. Preclinical data have suggested synergy between hypofractionated radiosurgery with immune checkpoint inhibitors such as PD1 and CTLA4 inhibitors. The purpose of this study is to evaluate feasibility and preliminary clinical efficacy of combining reirradiation using hypofractionated radiosurgery with concurrent nivolumab (PD1 inhibitor) plus or minus ipilimumab (CTLA4 inhibitor) for recurrent high-grade meningiomas. Methods: During the phase I portion, eligible patients will be treated according to treatment-escalation schema following the modified 3+3 design (Table). The maximum tolerated combination (MTC) will be the regimen at which ≤1/6 patients experience dose-limiting toxicity within 8 weeks of the start of study therapy. During the phase II portion, a total of 24 evaluable patients will be enrolled at the MTC using Simon’s MiniMax two-stage design. Key eligibility criteria include patients with recurrent grade II-III meningiomas after prior RT; age ≥ 18 years; ECOG score ≤ 2; measurable disease but ≤ 5 cm (or 20 cm3); prior radiation dose ≤ 70 Gy with at least 6 months interval; normal organ function; no active autoimmunity. The primary endpoints are to determine the MTC (phase I) and the objective response rate of the MTC (phase II). Secondary endpoints include safety, duration of response, progression-free survival, overall survival. Exploratory endpoints include developing an immune or molecular signature for predicting treatment response and resistance. The trial is actively enrolling and funded by the National Cancer Institute Experimental Therapeutics Clinical Trials Network (NCI-ETCTN). Treatment Escalation Schema. Clinical trial information: NCT03604978. [Table: see text]