785O PIVOT IO 001: First disclosure of efficacy and safety of bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) vs NIVO monotherapy in advanced melanoma (MEL)

Abstract

BEMPEG, an IL-2 prodrug, combined with NIVO, a PD-1 inhibitor, showed clinical activity with a manageable safety profile in patients (pts) with advanced MEL in the phase 1/2 PIVOT-02 study. These data supported initiation of the phase 3, randomized, open-label PIVOT IO 001 study (NCT03635983) evaluating BEMPEG + NIVO vs NIVO in advanced MEL. Here we report efficacy and safety of PIVOT IO 001. Pts with previously untreated, unresectable or metastatic MEL were randomized 1:1 to receive BEMPEG 0.006 mg/kg IV + NIVO 360 mg IV Q3W or NIVO 360 mg IV Q3W, stratified by PD-L1 tumor cell expression, BRAF mutation status, and AJCC v8 M stage. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS), both by blinded independent central review per RECIST v1.1, and overall survival (OS). Overall study α was 0.05, split with 0.001 for ORR, 0.03 for PFS, and 0.019 for OS. All α are 2-sided. 783 pts were randomized to BEMPEG + NIVO (n = 391) or NIVO (n = 392); baseline characteristics were balanced across arms. Median follow-up was 19.3 months (mo) and 11.6 mo for ORR and PFS, respectively. The ORR with BEMPEG + NIVO was 27.7% vs 36.0% with NIVO (2-sided P = 0.0311). Disease control rate was 56.1% with BEMPEG+ NIVO and 58.5% with NIVO. Median PFS with BEMPEG + NIVO was 4.17 mo (95% CI, 3.52–5.55) vs 4.99 mo (4.14–7.82) with NIVO; HR, 1.09 (97% CI, 0.88–1.35); P = 0.3988. Median OS was 29.67 mo (95% CI, 22.14–not reached [NR]) for BEMPEG + NIVO vs 28.88 mo (21.32–NR) with NIVO (HR, 0.94; 99.93% CI, 0.59–1.48; P = 0.6361). Grade 3–4 drug-related adverse events (AEs) and serious AEs were higher with BEMPEG + NIVO (21.7% and 10.1%) vs NIVO (11.5% and 5.5%). An AE of special interest, ischemic cerebrovascular events, was higher with BEMPEG + NIVO (2.6%) vs NIVO (0.8%). There were 3 BEMPEG + NIVO and 1 NIVO treatment-related deaths. In pts with advanced MEL, BEMPEG + NIVO demonstrated no added clinical efficacy vs NIVO. Primary endpoints ORR, PFS, and OS did not meet the prespecified boundary for statistical significance. Increased toxicity was observed with BEMPEG + NIVO vs NIVO. Ongoing biomarker analysis may help further interpret study results.