Bempegaldesleukin plus nivolumab in first-line advanced/metastatic urothelial carcinoma: Results from a phase II single-arm study (PIVOT-10).

BACKGROUND

In PIVOT-02, bempegaldesleukin (BEMPEG), a pegylated interleukin-2 cytokine prodrug, in combination with nivolumab (NIVO), a Programmed cell death protein 1 inhibitor, demonstrated the potential to provide additional benefits over immune checkpoint inhibitor monotherapy in patients with urothelial carcinoma, warranting further investigation. We evaluated BEMPEG plus NIVO in cisplatin-ineligible patients with previously untreated locally advanced or metastatic urothelial carcinoma.

METHODS

This open-label, multicenter, single-arm, phase II study enrolled patients with locally advanced/surgically unresectable or metastatic urothelial carcinoma and who were ineligible for cisplatin-based treatment. Patients received BEMPEG plus NIVO were administered intravenously every 3 weeks for ≤2 years or until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by blinded independent central review (BICR) in patients with low programmed death ligand-1 (PD-L1) expression. Secondary endpoints included ORR and duration of response in the overall population. Progression-free survival (PFS) and overall survival (OS) were exploratory endpoints.

RESULTS

One hundred and eighty-eight patients were enrolled; 123 patients were PD-L1 low (combined positive score [CPS] <10; 65.4%), 59 were PD-L1 high (31.4%; CPS ≥10), and 6 had PD-L1 status unknown (3.2%). ORR per blinded independent central review in patients with PD-L1-low tumors was 17.9% (95% confidence interval [CI] 11.6-25.8) while in all treated patients was 19.7% (95% CI 14.3-26.1). Median PFS and OS in the overall population were 3.0 months and 12.6 months, respectively. BEMPEG plus NIVO combination was well tolerated, with a safety profile similar to previously reported trials; no new or unexpected safety signals were reported.

CONCLUSIONS

BEMPEG plus NIVO did not meet the efficacy threshold for ORR in patients with previously untreated locally advanced or metastatic urothelial carcinoma and low PD-L1 expression.

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest ASR has received grants from Basilea Pharmaceutic, Bristol Myers Squibb, Janssen, Loxo, Merck, Millenium and Nektar and participated in advisory boards for Abbvie, Astellas, AstraZeneca, Basilea, Bicycle Therapeutics, Bristol Myers Squibb, Janssen, Loxo, Merck, Mirati, Nektar, Genetech, G1 Therapeutics, Gilead, Ideeya Biosciences, Immunomedics, Seattle Genetics and Taiho. MB has received grants from AAA, AstraZeneca, Bayer, Bristol Myers Squibb, Genentech, Genome & Company, Incyte, Merck, Nektar, Peloton Therapeutics, Pfizer, Roche, SeaGen, Tricon Pharmaceuticals, Xencor and received honoraria for ad boards from AstraZeneca, Bayer, BMS, Calithera Biosciences, Eisai, EMD Serono, Exelixis, Genomic Health, Janssen, Nektar, Pfizer, Sanofi and SeaGen. SS has received consulting fees from Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, BMS, Eisai, EMD Serono, Gilead, Ipsen, Janssen, Merck, Pfizer and Seagen and research funding from EMD Serono, Janssen and Seagen. KP has received consulting fees from Nektar and contracted research for AstraZeneca, Merck, Nektar, Pfizer, Regeneron Pharmaceuticals and Roche. TW is a shareholder of stocks in Nektar Therapeutics. AQ is a shareholder of stocks in Bristol Myers Squibb. MT is a shareholder of stocks at Nektar Therapeutics. JZ is a shareholder of stocks at Nektar Therapeutics. YL has received consulting fees and honoraria from Astellas, AstraZeneca, BMS, Gilead, Janssen, Merck KGaA, MSD, Pfizer, Roche, Seattle Genetics and Tahio and received support for travel from AstraZeneca, MSD and Pfizer. RH, AB, DC, UDG, AV, AP, RJ, HH, VK, SP have declared no conflicts of interest.