ASCO GU 2021: Nivolumab plus Ipilimumab in Patients with Advanced Non-Clear Cell Renal Cell Carcinoma (nccRCC): Safety and Efficacy from CheckMate 920

(UroToday.com) The long-term efficacy and tolerability of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W × 4 doses followed by nivolumab 3 mg/kg Q2W for previously untreated advanced renal cell carcinoma (RCC) demonstrated in the registrational CheckMate 214 clinical trial1 was based on patients with a predominantly clear cell component. Current data on the clinical activity of nivolumab plus ipilimumab in non-clear cell RCC are limited and largely based on retrospective analyses and thus prospective studies are needed. CheckMate 920 (NCT02982954) is a US community-based, multi-arm, phase IIIb/IV clinical trial of nivolumab plus ipilimumab treatment in patients with previously untreated advanced RCC and clinical features mostly excluded from phase III trials (ie non-clear cell RCC, brain metastases, and poor performance status). At the GU ASCO 2021 annual meeting, Dr. Scott Tykodi and colleagues presented the safety and efficacy results for cohort 2 patients with non-clear cell RCC from CheckMate 920, a patient population with a poor prognosis and without definitive effective treatment.


In CheckMate 920, patients with previously untreated advanced/metastatic non-clear cell RCC, Karnofsky performance status ≥ 70%, and any International Metastatic RCC Database Consortium (IMDC) risk received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W × 4 doses followed by nivolumab 480 mg Q4W for ≤ 2 years or until disease progression/unacceptable toxicity. The CheckMate 920 study design is as follows:

ASCO_GU_CheckMate_920.png



The primary endpoint was incidence of any-causality grade ≥ 3 immune-mediated adverse events within 100 days of last dose of study drug. Key secondary endpoints included progression-free survival and objective response rate by RECIST v1.1 (both per investigator), duration of response, and time to response. Exploratory endpoints included overall survival.

 Of the 52 treated patients with non-clear cell RCC in cohort 2, 69.2% were men, the median age was 64 years (range: 23–86), and 28.8% had sarcomatoid features. Histological subtypes were papillary (34.6%), chromophobe (13.5%), translocation associated (3.8%), collecting duct (3.8%), renal medullary (1.9%), or unclassified (42.3%). With 24.1 months minimum follow-up, median duration of therapy was 3.5 months (range: 0.0–25.8) for nivolumab and 2.1 months (range: 0.0–3.9) for ipilimumab. The median number of doses received was 4.5 (range: 1–28) for nivolumab and 4.0 (1–4) for ipilimumab. There were no grade 5 immune-mediated adverse events and grade 3–4 immune-mediated adverse events (n = 52) by category were diarrhea/colitis (7.7%), rash (5.8%), nephritis and renal dysfunction (3.8%), hepatitis (1.9%), adrenal insufficiency (1.9%), and hypophysitis (1.9%). The objective response rate (n = 46) was 19.6% (95% CI, 9.4–33.9), including two patients that achieved complete response (papillary, n = 1; unclassified pathology, n = 1), seven achieved partial response (papillary, n = 4; unclassified pathology, n = 3), and 17 patients had stable disease. Objective response rates by subgroups are as follows:

ASCO_GU_RECIST_v1.1.png



The median time to response was 2.8 months (range: 2.1–4.8), median duration of response was not reached (range: 0.03+–27.8+), and 8 of 9 responders remain without reported progression. Finally, the median progression-free survival was 3.7 months (95% CI, 2.7–4.6) and median overall survival was 21.2 months (95% CI, 16.6–not reached):


ASCO_GU_RCC_in_cohort.png


ASCO_GU_median_overall_survival.png



Dr. Tykodi concluded this presentation of the CheckMate 920 study cohort 2 patients with the following conclusions:

  • The safety profile of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W for four doses followed by nivolumab 480 mg Q4W for previously untreated advanced non-clear cell RCC was consistent with the known safety profile of nivolumab plus ipilimumab with no new signals identified
  • Encouraging antitumor activity and survival was observed with durable responses seen in patients with papillary and unclassified pathology
  • CheckMate 920 is the first prospective trial of nivolumab plus ipilimumab as first-line therapy for advanced metastatic non-clear cell RCC and adds to retrospective clinical evidence for this combination in a population with a high unmet medical need
  • The ongoing large phase 2 SUNNIFORECAST trial of nivolumab plus ipilimumab versus standard of care for previously untreated advanced non-clear cell RCC will provide additional data
Presented by: Scott S. Tykodi, MD, PhD, University of Washington, Seattle, WA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_mdduring the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021

References:

  1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carinoma. N Engl J Med 2018;378(14):1277-1290.
email news signup