ASCO GU 2022: A Phase I/II Study of Nivolumab and Axitinib in Patients With Advanced Renal Cell Carcinoma

( The 2022 GU ASCO Annual meeting included a renal cell carcinoma (RCC) session featuring work from Dr. Matthew Zibelman and colleagues presenting results of a phase I/II study of nivolumab and axitinib in patients with advanced RCC. Combination systemic therapy with tyrosine kinase inhibitors (TKIs) and an immune checkpoint inhibitor (IO) are an established standard of care for patients with metastatic RCC. This trial was performed to investigate the safety and efficacy of combining the TKI axitinib with the IO agent nivolumab.

 This phase I/II study investigated the combination of axitinib and nivolumab in an initial dose finding phase I portion with a 3+3 design to determine the recommended phase 2 dose (RP2D) of axitinib. The phase II portion included 2 parallel arms: treatment naïve metastatic RCC patients and metastatic RCC patients previously treated with TKIs alone or IO/IO combination (NCT03172754). This report focuses on results from the treatment naïve arm only. Included patients had to have histology with any clear cell component, ECOG performance status of 0-1, no known or symptomatic brain metastases, and no history of autoimmune disease. The RP2D of axitinib was 5 mg BID from the phase I portion and patients could be treated for up to 2 years. The primary endpoint of the phase II portion was objective response rate (ORR) per investigator assessment. The trial schema for this study is as follows:


There were 44 patients accrued to the treatment naïve arm. One withdrew consent and was replaced but is included in the safety analysis, while 42 patients are evaluable for efficacy. The median age was 65 years (IQR 56-72 years) and the group was predominantly male (84.1%) and white (95.5%). Using the IMDC risk group grading, 18 patients (40.9%) were favorable risk, 23 patients (52.3%) were intermediate risk and 3 patients (6.8%) were poor risk. As follows is a summary of the baseline characteristics: 



The median follow-up was 11.5 months. Best response data is notable for an ORR of 59.5% (95% CI 43.3%-74.4%), with only 1 patient (2.4%) experiencing primary progressive disease, for a disease control rate of 97.6% (95% CI 87.4%-99.9%). The best response and change in tumor volume is as follows:




Median progression free survival was 16.4 months (95% CI 10.2 - 21.2 months):




Median overall survival (OS) was not reached; the OS rate at 12 months was 87.1% (95% CI 68.7%-95.1%):




Adverse event data was similar to published data for IO/TKI combinations, with no grade 4-5 adverse events. There were 29 patients that experienced a grade 3 adverse event (70.7%), the most common of which was hypertension (41.5%), and 20.5% discontinued the study due to treatment-related toxicity.


Dr. Zibelman concluded this presentation of the phase I/II study of nivolumab and axitinib in patients with advanced RCC with the following take-home messages:

  • The combination of axitinib/nivolumab for treatment naïve patients with metastatic RCC demonstrated efficacy comparable to available IO/TKI combinations with a similar safety profile
  • Axitinib remains a well-tolerated VEGF TKI that pairs well with anti-PD1 targeted immune checkpoint blockade resulting in excellent clinical outcomes
  • Future follow-up will assess long-term outcomes in this cohort, as well as efficacy in the previously treated cohort (prior TKI or prior ipilimumab/nivolumab)


Presented By: Matthew R. Zibelman, MD, Fox Chase Cancer Center, Philadelphia, PA

Co-Authors: Michael Anthony Carducci, Yasser Ged, Ana M. Molina, Rahul Ravilla, David R. Shaffer, Courtney Lambert, Mahvish Tafseer, Rachel Basiura, Danielle Weismann, Rutika Kokate, Karthik Devarajan, Karen Ruth, R. Katherine Alpaugh, Fern Anari, Pooja Ghatalia, Daniel M. Geynisman, Elizabeth R. Plimack

Affiliations: Johns Hopkins Kimmel Cancer Ctr, Baltimore, MD, Johns Hopkins University, Baltimore, MD, Weill Cornell Medicine, New York, NY, Albany Medical Center, Albany, NY, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA


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 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022
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