A parallel cohort phase 2 study of regorafenib plus nivolumab for recurrent or metastatic solid tumors: results in patients with glioblastoma multiforme (gbm) or anaplastic astrocytoma (aa)

INTRODUCTION The multikinase inhibitor regorafenib improved overall survival (OS) versus lomustine in relapsed GBM in the randomized phase 2 REGOMA study. The aim of this study was to evaluate the efficacy of regorafenib combined with nivolumab in this setting (NCT04704154). METHODS Patients aged ≥ 18 years with recurrent GBM/AA (WHO 2016 classification) after radiotherapy plus temozolomide, and an ECOG performance status (PS) of 0/1, received oral regorafenib 90 mg/day on days 1–21 and intravenous nivolumab 480 mg on day 1 of each 28-day cycle. If tolerated, the regorafenib dose could be escalated to 120 mg/day from cycle 2. Prior regorafenib treatment or immunotherapy was not allowed. The primary endpoint was objective response rate (ORR) using RANO criteria. Secondary endpoints included progression-free survival (PFS), OS, and safety (MedDRA; CTCAE v5.0). RESULTS Of the 36 patients enrolled, 30 were treated and were eligible for analysis. Median age was 60 years, 63% had an ECOG PS of 1, and 90% had GBM (10% AA). All patients discontinued treatment as of the primary analysis (March 9, 2023). One patient had a best-overall partial response (ORR; 3%) and nine (30%) had stable disease. Median number of cycles of regorafenib and nivolumab infusions was three. Median PFS (RANO) was 2.7 months (80% CI 1.8, 7.3) and 6-month PFS was 31.5%. Median OS was 8.0 months (80% CI 4.6, 12.4) and 12-month OS was 33.7%. Thirteen patients (43%) had grade 3/4 treatment-emergent adverse events (TEAEs), which were drug-related in 12 patients (40%). The most common drug-related grade 3/4 TEAEs were AST increase (13%), ALT increase (10%), and hypertension (10%). There were no immune-mediated serious TEAEs or drug-related grade 5 TEAEs. CONCLUSION The efficacy results of this study do not support further evaluation of regorafenib combined with nivolumab in GBM/AA. The safety profile was acceptable and manageable.