Bempegaldesleukin plus nivolumab in first-line renal cell carcinoma: results from the PIVOT-02 study

• Published in: Journal for immunotherapy of cancer Vol. 10; no. 4; p. e004419
• Main Authors: Tannir, Nizar M, Cho, Daniel C, Diab, Adi, Sznol, Mario, Bilen, Mehmet A, Balar, Arjun V, Grignani, Giovanni, Puente, Erika, Tang, Lily, Chien, David, Hoch, Ute, Choudhury, Arkopal, Yu, Danni, Currie, Sue L, Tagliaferri, Mary A, Zalevsky, Jonathan, Siefker-Radtke, Arlene O, Hurwitz, Michael E
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.04.2022; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original research
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biomarkers; Cancer therapies; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Clinical/Translational Cancer Immunotherapy; Cytokines; Drug dosages; Drug Therapy, Combination; Female; Humans; Immune checkpoint inhibitors; Immunotherapy; Interleukin-2 - therapeutic use; Kidney cancer; Kidney Neoplasms; Kidney Neoplasms - drug therapy; Kidney Neoplasms - pathology; Kinases; Lymphocytes; Male; Metastasis; Monoclonal antibodies; Nivolumab - therapeutic use; Patients; Response rates; Targeted cancer therapy; Tumors; United States > US; California; Drug Therapy, Combination; Kidney Neoplasms; Immunotherapy
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2021-004419

BackgroundImmune 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.MethodsThis 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.ResultsAt 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.ConclusionsBEMPEG 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.