Phase II Trial of Intermittent Therapy in Patients with Metastatic Renal Cell Carcinoma Treated with Front-line Ipilimumab and Nivolumab

In this study, patients with metastatic renal cell carcinoma (mRCC) who responded to treatment with ipilimumab and nivolumab were taken off therapy. Most (78%) of the patients who discontinued therapy per protocol have remained off therapy, with a median treatment-free interval of 34.3 months (range, 8.7-41.8), suggesting that a subset of patients with mRCC do not require extended immunotherapy treatment. Introduction: The combination of ipilimumab/nivolumab is approved for patients with treatment-na & iuml;ve, intermediate-, and poor-risk metastatic renal cell carcinoma (mRCC), but duration of therapy and safety/efficacy of reinduction at progression is unknown. A phase II trial of intermittent ipilimumab/nivolumab with reinduction at progression was conducted (NCT03126331). Patients and Methods: Patients with treatment-naive mRCC were treated with induction ipilimumab/nivolumab followed by up to 24 weeks of maintenance nivolumab. Patients who achieved a complete response (CR) or partial response (PR) were eligible for inclusion and entered a treatment-free observation period. Patients were restaged every 12 weeks. Patients with no disease progression (PD) remained off therapy. Upon PD, patients were re-challenged with 2 doses of ipilimumab/nivolumab every 3 weeks. Study objectives were to estimate success rate of observation in patients who achieve a CR/PR, and to assess toxicity in patients undergoing reinduction. The study accrued slower than expected and was closed prior to the anticipated accrual goal of 20 patients. Results: Nine patients were included; 89% male, median age 57, 67% clear-cell histology, and 78% intermediate-risk by IMDC criteria. Response to ipilimumab/nivolumab followed by nivolumab maintenance prior to enrollment was 33% CR and 67% PR. Most (78%) patients have remained off therapy, with a median treatment-free interval (TFI) of 34.3 months (range, 8.7-41.8). Two patients had PD off therapy and received 2 cycles of reinduction ipilimumab and nivolumab. No grade 3 or greater toxicities occurred with reinduction. Both patients developed PD at their first scans after reinduction. Conclusion: This prospective study demonstrates that patients with a radiographic response to ipilimumab/nivolumab can have prolonged treatment-free intervals. Further studies of de-escalation strategies are warranted. (c) 2024 The Authors. Published by Elsevier Inc.