Results from the prior treatment cohort of a phase I/II study of nivolumab and axitinib in patients with advanced renal cell carcinoma.

548 Background: Combination tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (IO) are an established standard of care for patients with metastatic renal cell carcinoma (mRCC). We report updated analysis of a multi-center, investigator-initiated (IIT), phase I/II study of axitinib (axi) with nivolumab (nivo) in the previously treated patient cohort. Methods: The study investigated the combination of axi/nivo in an initial dose finding phase I portion and a phase II portion including 2 parallel arms: treatment naïve mRCC patients and mRCC patients previously treated with TKIs or IO/IO combination (NCT03172754). We are presenting final results from the previously treated cohort. Included patients had pathology with any clear cell component, ECOG performance status of 0-1, no known or symptomatic brain metastases, and no history of autoimmune disease. The recommended phase 2 dose of axi was 5 mg BID and patients were treated for up to 2 years then could stop one or both therapies. The primary endpoint of the phase II portion was objective response rate (ORR) per investigator assessment. Results: Twenty-six patients were accrued to the previously treated arm, all evaluable for efficacy and toxicity. The median age was 62 yrs (range: 42-81), 80.8% were male and 88.5% were white. Twenty pts had 1 prior line of therapy (18 TKI alone), 6 pts had 2 or more prior lines of Tx. Two pts had prior nivo with ipilimumab. Median follow-up was 47.2 months. The ORR was 30.8% (all PRs) and 57.7% achieved stable disease. The primary PD rate was 11.5%. Median OS was 48.4 months and median PFS was 13.0 months. Six pts (23.1%) completed two years of Tx on trial and elected to stop one or both drugs (2 elected to stay on axi alone). Five pts remain progression-free and have received no subsequent therapy with a median progression-free interval of 23.2 months. None had received prior IO. Adverse event (AE) data was similar to published data for IO/TKI combinations. There was one Gr4 TRAE of elevated lipase and 12 pts (46%) experienced a Gr3 TRAE. One pt (4%) discontinued the study due to TRAEs. Conclusions: Final results from the previously treated cohort of this IIT of axi/nivo for pts with mRCC demonstrated an ORR of 30.8% and a DCR of 88.5% with no unexpected AEs. Though there were no CRs, disease control rate and median OS were encouraging in this previously treated population. This is the only reported IO/TKI trial that allowed for stopping of all Tx at 2 years, with 6 pts (23.1%) meeting this milestone, 5 of whom (19% of all pts) remain progression-free for a median period close to 2 years. Clinical trial information: NCT03172754 .