PURPOSE: Copanlisib in combination with immune checkpoint inhibitors (ICIs) demonstrated synergy and favorable anti-tumor immune responses in preclinical models. This study evaluated copanlisib plus nivolumab in adults with advanced solid tumors. PATIENTS AND METHODS: In this Phase Ib, non-randomized, open-label, dose-escalation study, patients received intravenous nivolumab 240 mg (day 15 of cycle 1 and days 1 and 15 of subsequent cycles) plus intravenous copanlisib (45 or 60 mg on days 1, 8, and 15 of each cycle) in 28-day cycles. The primary objective was to determine the maximum tolerated dose and/or recommended Phase II dose (RP2D) of copanlisib plus nivolumab. Secondary objectives were safety, tolerability, and efficacy. Exploratory objectives included evaluation of potentially predictive biomarkers. RESULTS: Overall, 16 patients were treated (copanlisib: 45 mg [n=5]
60 mg [n=11]). The most common cancer types at baseline were bladder (25.0%) and oropharyngeal (18.8%). No dose-limiting toxicities were observed
copanlisib 60 mg was deemed the RP2D in combination with nivolumab 240 mg. Grade 3 and 4 treatment-emergent adverse events were reported in 56.3% and 12.5% of patients, respectively
one grade 5 event was reported (unrelated to treatment). Overall, 18.8% of patients achieved a partial response. Evaluations of potential biomarkers did not correlate with response, but copanlisib-modulated biomarker changes were observed before nivolumab administration and were consistent and dose-dependent. CONCLUSIONS: No new safety concerns were identified with this combination, and preliminary efficacy indicated an anti-tumor effect. Data supported an immunomodulatory effect of copanlisib, suggesting that this combination may enhance the efficacy of ICIs.