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

• Type of Material: Article
• Authors: Nizar M Tannir, University of Texas MD Anderson Cancer Center; Daniel C Cho, New York Medical College; Adi Diab, University of Texas MD Anderson Cancer Center; Mario Sznol, Yale Cancer Center; Mehmet Bilen, Emory University; Arjun Balar, New York Medical College; Giovanni Grignani, FPO IRCCS; Erika Puente, Nektar Therapeutics; Lily Tang, Nektar Therapeutics; David Chien, Nektar Therapeutics; Ute Hoch, Nektar Therapeutics; Arkopal Choudhury, Nektar Therapeutics; Danni Yu, Nektar Therapeutics; Sue L Currie, Nektar Therapeutics; Mary A Tagliaferri, Nektar Therapeutics; Jonathan Zalevsky, Nektar Therapeutics; Arlene O Siefker-Radtke, University of Texas MD Anderson Cancer Center; Michael E Hurwitz, Yale Cancer Center
• Language: English
• Date: 2022-04-01
• Publisher: BMJ PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/jitc-2021-004419
• Title of Journal or Parent Work: JOURNAL FOR IMMUNOTHERAPY OF CANCER
• Volume: 10
• Issue: 4
• Grant/Funding Information: This trial was designed and funded by the sponsor (Nektar Therapeutics). The sponsor and their representatives collected and analyzed the data. All authors had full access to study data, and the corresponding author had final responsibility for the decision to submit for publication.
• Keywords: Immunology; INTERLEUKIN-2; Oncology; NKTR-214; Kidney Neoplasms; ACTIVATION; SUNITINIB; CABOZANTINIB; Drug Therapy; Life Sciences & Biomedicine; Combination; Immunotherapy; Science & Technology; EFFICACY
• Research Categories: Health Sciences, Oncology

Abstract

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.