CTNI-48. NERATINIB FOR <i>NF2</i> -RELATED SCHWANNOMATOSIS WITH PROGRESSIVE TUMORS: INTERIM ANALYSIS FROM THE INTUITT-NF2 PLATFORM-BASKET TRIAL

Abstract BACKGROUND NF2-related schwannomatosis (NF2-SWN) predisposes affected individuals to vestibular schwannomas (VS), non-vestibular schwannomas (NVS), meningiomas, and ependymomas. Previous trials of erbB1/EGFR and erbB2/HER2 inhibitors have shown some efficacy against VS. Neratinib is a potent irreversible pan-erbB inhibitor. We report the results of the interim analysis of the neratinib treatment arm of INTUITT-NF2. METHODS We conducted a multicenter, phase II, open-label basket trial of neratinib for subjects (≥12 years old) with NF2-SWN and progressive tumors (baskets: VS, NVS, meningioma, or ependymoma). Twenty participants were accrued (≥2 participants per basket). Tumor response was evaluated by MRI every 3 months in year 1 and every 6 months thereafter. Radiographic response was defined as ≥20% decrease in tumor volume below baseline. Primary outcome was the radiographic response rate (RR). Pre- and post-treatment growth rates were determined using pre-baseline and study MRI scans. RESULTS Twenty subjects (median age=27 years; range, 12-45 years) were treated with neratinib. Target tumors included 10 VS, 3 NVS, 5 meningiomas, and 2 ependymomas; non-target tumors included 20 VS, 14 NVS, 13 meningiomas, and 2 ependymomas. Radiographic RR for target and all tumors was 10% and 13%, respectively. By tumor basket, radiographic RR for all tumors was 0% for VS, 35% for non-VS, 17% for meningioma, and 0% for ependymomas. Average annualized tumor growth rates decreased for VS, NVS, meningioma, and ependymoma during neratinib treatment. There were no serious adverse events and five grade 3 treatment-related adverse events (all diarrhea). Three patients held or delayed dose due to grade 2/3 toxicity (diarrhea, rash, malaise), and two discontinued treatment during cycle 1 (diarrhea, malaise). CONCLUSIONS Neratinib treatment showed modest efficacy in treatment of tumors associated with NF2-SWN. Based on this interim analysis, the team will explore whether an additional 20 participants will be enrolled in the two most promising tumor baskets.