PIVOT-10: Bempegaldesleukin, Nivolumab Well-Tolerated, but Lacks Beneficial ORR

The PIVOT-02 study analyzed the use of bempegaldesleukin (BEMPEG), a pegylated interleukin-2 cytokine prodrug, in combination with nivolumab for the treatment of advanced/metastatic urothelial carcinoma (aUC).

The combination provided beneficial antitumor activity in patients as a first-line treatment, and displayed benefits over immune checkpoint inhibitor monotherapy. The PIVOT-10 trial has expanded on this research by further investigating this treatment combination in cisplatin-ineligible patients with previously untreated mUC.

The phase II, open-label, multicenter study enrolled 188 patients with mUC or locally advanced and surgically unresectable UC who were ineligible for cisplatin-based therapy. Patients were administered intravenous BEMPEG plus nivolumab every 3 weeks for ≤2 years or until progression or unacceptable toxicity.

The primary endpoint was objective response rate (ORR) in patients with low programmed death ligand-1 (PD-L1) expression, while secondary endpoints included ORR and duration of response in the study’s overall population. Progression-free survival (PFS) and overall survival (OS) were also measured as exploratory endpoints.

Out of 188 patients, 123 were PD-L1 low (combined positive score [CPS] <10; 65.4%), 59 were PD-L1 high (31.4%; CPS ≥10), and 6 had an unknown PD-L1 status (3.2%). The ORR in patients with PD-L1-low tumors was 17.9% (95% CI 11.6-25.8), and 19.7% in all treated patients (95% CI 14.3-26.1).

In the overall study population, the median PFS and OS were 3 and 12.6 months, respectively. While BEMPEG plus nivolumab was well-tolerated, the combination did not meet the efficacy threshold for ORR in the study’s patient population.