PIVOT IO 001 study: No additional clinical benefit of BEMPEG plus NIVO combination therapy versus NIVO monotherapy for previously untreated unresectable or metastatic melanoma
October 17, 2023
Abstract
PURPOSE:
Despite marked advances in the treatment of unresectable or metastatic melanoma, the need for novel therapies remains. Bempegaldesleukin (BEMPEG), a pegylated interleukin-2 (IL-2) cytokine prodrug, demonstrated efficacy in the phase II PIVOT-02 trial. PIVOT IO 001 (ClinicalTrials.gov identifier: NCT03635983) is a phase III, randomized, open-label study that builds on the PIVOT-02 results in first-line melanoma.
METHODS:
Patients with previously untreated, unresectable, or metastatic melanoma were randomly assigned 1:1 to receive BEMPEG plus nivolumab (NIVO) or NIVO monotherapy. Primary end points were objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review and overall survival (OS). Secondary and exploratory end points included additional efficacy measures, safety, and pharmacokinetics (PKs) and pharmacodynamics analyses.
RESULTS:
In 783 patients (n = 391, BEMPEG plus NIVO; n = 392, NIVO monotherapy), the median follow-up was 11.6 months in the intent-to-treat population. The ORR with BEMPEG plus NIVO was 27.7% versus 36.0% with NIVO (two-sided P = .0311). The median PFS with BEMPEG plus NIVO was 4.17 months (95% CI, 3.52 to 5.55) versus 4.99 months (95% CI, 4.14 to 7.82) with NIVO (hazard ratio [HR], 1.09; 97% CI, 0.88 to 1.35; P = .3988). The median OS was 29.67 months (95% CI, 22.14 to not reached [NR]) with BEMPEG plus NIVO versus 28.88 months (95% CI, 21.32 to NR) with NIVO (HR, 0.94; 99.929% CI, 0.59 to 1.48; P = .6361). Grade 3-4 treatment-related adverse events (AEs) and serious AE rates were higher with the combination (21.7% and 10.1%, respectively) versus NIVO (11.5% and 5.5%, respectively). BEMPEG PK exposure and absolute lymphocyte count changes after BEMPEG plus NIVO were comparable between PIVOT IO 001 and PIVOT-02.
CONCLUSION:
The PIVOT IO 001 study did not meet its primary end points of ORR, PFS, and OS. Increased toxicity was observed with BEMPEG plus NIVO versus NIVO.
Source:
Diab, A., Gogas, H., Sandhu, S., Long, G. V., Ascierto, P. A., Larkin, J., Sznol, M., Franke, F., Ciuleanu, T. E., Pereira, C., Muñoz Couselo, E., Bronzon Damian, F., Schenker, M., Perfetti, A., Lebbe, C., Quéreux, G., Meier, F., Curti, B. D., Rojas, C., … Khushalani, N. I. (2023). Bempegaldesleukin plus nivolumab in untreated advanced melanoma: The open-label, phase III pivot IO 001 trial results. Journal of Clinical Oncology. https://doi.org/10.1200/jco.23...