Bempegaldesleukin plus nivolumab in first-line advanced/metastatic urothelial carcinoma: Results from a phase II...

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.

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.

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.

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.