PIVOT IO 001: First disclosure of efficacy and safety of bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) vs NIVO monotherapy in advanced melanoma (MEL)
Presented at the ESMO Congress: Proffered Paper session 1: Melanoma and other skin tumours. A. Diab1, H.J. Gogas2, S.K. Sandhu3, G.V. Long4, P.A. Ascierto5, J. Larkin6, M. Sznol7, F.A. Franke8, T. Ciuleanu9, E. Muñoz Couselo10, A. Perfetti11, C. Lebbe12, F. Meier13, B. Curti14, C. Rojas15, H. Yang16, M. Zhou16, S. Ravimohan17, M.A. Tagliaferri18, N. Khushanlani19
Background 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. Methods 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. Results 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. Conclusions 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. Clinical trial identification NCT03635983.