Safety and efficacy outcomes with nivolumab plus ipilimumab in patients with advanced renal cell carcinoma and brain metastases: results from the CheckMate 920 trial.
Authors: Hamid Emamekhoo, Mark R Olsen, Bradley Curtis Carthon, Alexandra Drakaki, Ivor John Percent, Ana M. Molina, Daniel C. Cho, Johanna C. Bendell, Lucio N. Gordan, Arash Rezazadeh Kalebasty, Daniel J. George, Thomas E. Hutson, Edward Arrowsmith, Joshua Zhang, Jesus Zoco, Jennifer L. Johansen, David Leung, Scott S. Tykodi
Journal: Journal of Clinical Oncology (2021)

4515 Background: Combination therapy with nivolumab plus ipilimumab (NIVO+IPI) has demonstrated long-term efficacy and tolerability in patients with previously untreated advanced renal cell carcinoma (aRCC). Previous phase 3 clinical trials of patients with advanced or metastatic cancers have mostly excluded patients with brain metastases. CheckMate 920 is an ongoing, phase 3b/4 clinical trial of NIVO+IPI treatment in patients with aRCC with a high unmet medical need. We present updated safety and efficacy results for the cohort of patients with aRCC of any histology and brain metastases from CheckMate 920 (NCT02982954). Methods: Patients with previously untreated advanced/metastatic aRCC of any histology, with asymptomatic brain metastases (not currently receiving corticosteroids or radiation), and Karnofsky performance status ≥ 70% were assigned to treatment with NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks × 4 doses followed by NIVO 480 mg every 4 weeks for ≤ 2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥ 3 immune-mediated adverse events (imAEs) within 100 days of last dose of study drug. Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 (both per investigator). Exploratory endpoints included overall survival (OS). Results: Of 28 treated patients with brain metastases, 85.7% were men; median (range) age was 60 (38–87) years, and 14.3% had sarcomatoid features. With 24.5 months minimum follow-up of the 28 patients enrolled, median duration of therapy (range) was 3.4 (0.0–23.3) months for NIVO and 2.1 (0.0–3.3) months for IPI. No grade 5 imAEs occurred. Grade 3–4 imAEs by category were diarrhea/colitis (7.1%), hypophysitis (3.6%), rash (3.6%), hepatitis (3.6%), and diabetes mellitus (3.6%). Of the 25 patients who were evaluable for ORR, the ORR was 32.0% (95% CI, 14.9–53.5). No patients achieved complete response, 8 achieved partial response, and 10 patients had stable disease. Median time to response (range) was 2.8 (2.4–3.0) months. Median duration (range) of response was 24.0 (3.9–not estimable [NE]) months; 4 of 8 responders remain without reported progression. Of 28 patients, 7 (25%) had intracranial progression. Median PFS (n = 28) was 9.0 (95% CI, 2.9–12.0) months. Median OS (n = 28) was still not reached (95% CI, 14.1 months–NE). Conclusions: In patients with previously untreated aRCC and brain metastases, a population with high unmet medical need that is often underrepresented in clinical trials, the approved treatment regimen of NIVO+IPI followed by NIVO for aRCC showed no new safety signals and continues to show encouraging antitumor activity with longer follow-up. Clinical trial information: NCT02982954.