EIKCS 2022: Nivolumab + Ipilimumab + Cabozantinib for Previously Untreated Advanced RCC: Results from a Discontinued Study Arm of CheckMate 9ER

(UroToday.com) The 2022 International Kidney Cancer Symposium (IKCS) European Annual meeting included an oral abstract session and presentation by Dr. Bernard Escudier discussing nivolumab + ipilimumab + cabozantinib for previously untreated advanced renal cell carcinoma (RCC), which was a discontinued study arm in the phase 3 CheckMate 9ER trial. Dr. Escudier notes that the CheckMate 9ER trial1 originally included three treatment arms to compare outcomes for nivolumab + cabozantinib versus sunitinib and nivolumab + ipilimumab + cabozantinib versus sunitinib. Shortly after CheckMate 9ER began, data from CheckMate 2142 demonstrated the OS superiority of nivolumab + ipilimumab versus sunitinib for patients with IMDC intermediate- or poor-risk untreated advanced RCC, suggesting a likely future role for nivolumab + ipilimumab as standard of care for this population. Based on this evolving advanced RCC treatment landscape, evaluation of nivolumab + ipilimumab + cabozantinib versus sunitinib was no longer considered appropriate, and the CheckMate 9ER triplet arm was discontinued early via a protocol amendment.

Dr. Escudier presented results of an exploratory efficacy and safety analysis for the small cohort of patients randomized to nivolumab + ipilimumab + cabozantinib in CheckMate 9ER before enrollment discontinuation. Data presented are from a June 24, 2021 database lock, with an extended median follow-up for overall survival of 39.1 (range: 33.4-44.5) months.

The CheckMate 9ER study design is as follows:

CheckMate 9ER-0.jpg

There were 50 patients that were randomized to nivolumab + ipilimumab + cabozantinib, with a median age of 60 years (range: 40-84), most of the patients being IMDC intermediate risk (62%), the majority having >= 2 targeted lesions (90%), and the most common site of metastasis being the lung (68%) followed by lymph nodes (48%). The median progression-free survival per BICR was 9.9 months (95% CI 5.7-16.8) and per investigator was 13.9 months (95% CI 7.3-24.7):

CheckMate 9ER-1.jpg

Furthermore, the median overall survival was 37.0 months (95% CI 31.8 - not evaluable) and the 2-year overall survival rate was 73.3% (95% CI 58.4 – 83.5):

CheckMate 9ER-2.jpg

The objective response rate per BICR was 44.0% (95% CI 30.0-58.7) and per investigator, assessment was 48.0% (95% CI 33.7-62.6), which included 4 (8.0%) patients with a complete response by BICR assessment. The median time to response was 2.8 months (IQR 2.6-4.2) and the median duration of response was 21.4 months (IQR 13.8-30.6). Treatment exposure and discontinuation data are as follows:

CheckMate 9ER-3.jpg

In total, 42 patients (84%) experienced >= 1 grade 3-4 treatment-related adverse events, and no patients experienced a grade 5 adverse event. Overall, 6 patients (12%) discontinued all study treatment within 6 months due to a treatment-related hepatic adverse event, which was the most common reason for discontinuation due to study drug toxicity within the first 6-12 months of treatment. Overall, 44% of patients had a subsequent therapy and 40% of patients had a subsequent systemic therapy, most commonly a VEGF inhibitor (n=17, 34%).

Dr. Escudier concluded his presentation of nivolumab + ipilimumab + cabozantinib for previously untreated advanced RCC with the following take-home messages:

  • Efficacy results from this exploratory analysis add to existing evidence suggesting clinical activity of nivolumab + ipilimumab + cabozantinib across multiple tumor types, and provide preliminary insights into possible outcomes among patients with untreated advanced RCC
  • The safety profile of nivolumab + ipilimumab + cabozantinib was generally consistent with that reported in a prior phase 1 study of the triplet combination in various GU tumors, including advanced RCC
  • Efficacy and safety reported here should be interpreted in the context of the patient demographics and limited experience with triplet regimen at the time of enrollment
  • Further study of this triplet regimen in RCC populations is ongoing, with a more definitive efficacy and safety evaluation in advanced RCC underway in the phase 3 COSMIC-313 trial (NCT03937219) of nivolumab + ipilimumab + cabozantinib versus nivolumab + ipilimumab for patients with intermediate- or poor-risk, previously untreated disease

Presented by: Bernard Escudier, MD, Medical Oncologist, Institut Gustave Roussy, Villejuif, France

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 International Kidney Cancer Symposium (IKCS) Europe Annual Hybrid Meeting, Antwerp, Belgium, Fri, Apr 22 – Sun, Apr 24, 2022.


  1. Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2021 Mar 4;384(9):829-841.
  2. 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.