Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial

Abstract

Purpose: Nivolumab is a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody that restores T-cell immune activity. This phase II trial assessed the antitumor activity, dose-response relationship, and safety of nivolumab in patients with metastatic renal cell carcinoma (mRCC).

Patients and methods: Patients with clear-cell mRCC previously treated with agents targeting the vascular endothelial growth factor pathway were randomly assigned (blinded ratio of 1:1:1) to nivolumab 0.3, 2, or 10 mg/kg intravenously once every 3 weeks. The primary objective was to evaluate the dose-response relationship as measured by progression-free survival (PFS); secondary end points included objective response rate (ORR), overall survival (OS), and safety.

Results: A total of 168 patients were randomly assigned to the nivolumab 0.3- (n = 60), 2- (n = 54), and 10-mg/kg (n = 54) cohorts. One hundred eighteen patients (70%) had received more than one prior systemic regimen. Median PFS was 2.7, 4.0, and 4.2 months, respectively (P = .9). Respective ORRs were 20%, 22%, and 20%. Median OS was 18.2 months (80% CI, 16.2 to 24.0 months), 25.5 months (80% CI, 19.8 to 28.8 months), and 24.7 months (80% CI, 15.3 to 26.0 months), respectively. The most common treatment-related adverse event (AE) was fatigue (24%, 22%, and 35%, respectively). Nineteen patients (11%) experienced grade 3 to 4 treatment-related AEs.

Conclusion: Nivolumab demonstrated antitumor activity with a manageable safety profile across the three doses studied in mRCC. No dose-response relationship was detected as measured by PFS. These efficacy and safety results in mRCC support study in the phase III setting.

Trial registration: ClinicalTrials.gov NCT01354431.

Fig 1.

Patient disposition (as of May 15, 2013, data cutoff). (*) One patient not treated; no longer met study criteria. (†) Includes patients continuing in treatment period and patients in follow-up period.

Fig 2.

(A) Progression-free and (B) overall survival by treatment arm (randomly assigned patients). Tick marks represent censored observations.

Fig 3.

Duration of response in patients who achieved objective response by dose treatment arm. Based on data cutoff date of March 5, 2014.

Fig 4.

Overall survival (randomly assigned patients) by (A) Memorial Sloan-Kettering Cancer Center risk group and (B) number of prior therapies in advanced or metastatic setting. Tick marks represent censored observations.

Fig A1.

Changes in measurable lesions from study baseline in patients treated beyond progression (n = 36 [0.3 mg/kg, n = 10; 2 mg/kg, n = 12; 10 mg/kg, n = 14]). Circles represent assessments that occurred after initial progression.