Phase II study of axitinib intensification compared to nivolumab alone after induction with ipilimumab plus nivolumab in patients with mRCC without previous complete response (AxIn study)

Background: The combination of nivolumab plus ipilimumab (N+I) is able to increase the overall survival (OS), progression free survival (PFS) and overall response rate (ORR) compared to sunitinib in patients (pts) with metastatic renal cell carcinoma (mRCC) at intermediate or poor prognosis. However, the rate of pts with partial response to N+I (32%) is lower of that reported with the combination of axitinib plus pembrolizumab (51%). Moreover, analysis of outcome based on the depth of response strongly suggests a connection between response and survival. This study aims at investigating the efficacy of an intensified strategy with axitinib added to nivolumab in mRCC pts without complete response at the end of N+I induction. Methods: AxIn study (NCT05817903) is a randomized, open-label, multicenter, phase 2 trial evaluating in mRCC pts who completed induction with N+I without complete response or progressive disease, whether the intensification of therapy by adding axitinib to the standard nivolumab can increase the response rate and improve the survival compared to nivolumab alone. Eligible pts with partial response or stable disease after completion of N+I induction as first-line therapy, without any toxicity ≥ G2, and candidates to maintenance nivolumab as per standard clinical practice will be randomized 1:1 to intensification of therapy with axitinib in addition to nivolumab (Arm A) or nivolumab alone (Arm B). The primary endpoint is to assess the ORR of pts treated with the intensification of axitinib plus nivolumab compared to the standard of care of nivolumab monotherapy. Secondary endpoints include PFS, OS, depth of response, duration of response, quality of life, and safety. Exploratory biomarkers analysis will be performed. The trial is actively recruiting. Clinical trial information: NCT05817903.