Bempegaldesleukin Plus Nivolumab in First-Line Renal Cell Carcinoma: Results From the PIVOT-02 Study
BACKGROUND: Immune checkpoint inhibitor-based combinations have expanded the treatment options for patients with renal cell carcinoma (RCC); however, tolerability remains challenging. The aim of this study was to evaluate the safety and efficacy of the immunostimulatory interleukin-2 cytokine prodrug bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) as first-line therapy in patients with advanced clear-cell RCC. METHODS: This was an open-label multicohort, multicenter, single-arm phase 1/2 study; here, we report results from the phase 1/2 first-line RCC cohort (N=49). Patients received BEMPEG 0.006 mg/kg plus NIVO 360 mg intravenously every 3 weeks. The primary objectives were safety and objective response rate (ORR; patients with measurable disease at baseline and at least one postbaseline tumor response assessment). Secondary objectives included overall survival (OS) and progression-free survival (PFS). Exploratory biomarker analyses: association between baseline biomarkers and ORR. RESULTS: At a median follow-up of 32.7 months, the ORR was 34.7% (17/49 patients); 3/49 patients (6.1%) had a complete response. Of the 17 patients with response, 14 remained in response for >6 months, and 6 remained in response for >24 months. Median PFS was 7.7 months (95% CI 3.8 to 13.9), and median OS was not reached (95% CI 37.3 to not reached). Ninety-eight per cent (48/49) of patients experienced ≥1 treatment-related adverse event (TRAE) and 38.8% (19/49) had grade 3/4 TRAEs, most commonly syncope (8.2%; 4/49) and increased lipase (6.1%; 3/49). No association between exploratory biomarkers and ORR was observed. Limitations include the small sample size and single-arm design. CONCLUSIONS: BEMPEG plus NIVO showed preliminary antitumor activity as first-line therapy in patients with advanced clear-cell RCC and was well tolerated. These findings warrant further investigation.
Tannir, N. M., Cho, D. C., Diab, A., Sznol, M., Bilen, M. A., Balar, A. V., Grignani, G., Puente, E., Tang, L., Chien, D., Hoch, U., Choudhury, A., Yu, D., Currie, S. L., Tagliaferri, M. A., Zalevsky, J., Siefker-Radtke, A. O., & Hurwitz, M. E. (2022). Bempegaldesleukin Plus Nivolumab in First-Line Renal Cell Carcinoma: Results From the PIVOT-02 Study. https://doi.org/10.1136/jitc-2021-004419