Safety and efficacy of first-line nivolumab plus ipilimumab alternating with nivolumab monotherapy in patients with advanced renal cell carcinoma: the non-randomised, open-label, phase IIIb/IV CheckMate 920 trial

Objectives The non-randomised, open-label, phase IIIb/IV multicohort CheckMate 920 trial explored the safety and efficacy with a less frequent, but continual nivolumab plus ipilimumab (NIVO+IPI) dosing regimen (cohort 1) to determine whether this modification could potentially retain efficacy benefits while improving on the manageable safety profile previously observed with this combination in patients with advanced renal cell carcinoma (aRCC). Setting Patients were enrolled from 48 largely community-based sites in the USA. Participants 106 patients with previously untreated, predominantly clear cell aRCC received treatment. Interventions Patients received NIVO 6 mg/kg plus IPI 1 mg/kg on day 1 of the first week of each 8-week cycle; the combination alternated with NIVO 480 mg monotherapy on day 1 of the fifth week of each 8-week cycle. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or study end. The maximum treatment duration was 2 years. The primary endpoint was the incidence of high-grade (grade 3/4 and grade 5) immune-mediated adverse events (IMAEs) within 100 days of the last dose. Select secondary endpoints included time to onset and resolution of high-grade IMAEs, progression-free survival (PFS) and objective response rate (ORR). The incidence of treatment-related adverse events and the overall survival (OS) were the exploratory endpoints. Results The most common grade 3/4 IMAEs were diarrhoea/colitis (7.5%) and rash (6.6%) and no grade 5 IMAEs occurred, with a minimum follow-up of 28.5 months. The median PFS was 4.8 (95% CI 3.0 to 8.3) months, the ORR in evaluable patients (n=96) was 34.4% (95% CI 25.0 to 44.8), and the median OS was not reached (95% CI 24.8 months to not estimable). Conclusions While no new safety signals were reported with less frequent, but continual NIVO+IPI dosing in CheckMate 920, the modified regimen was not associated with clinical benefits relative to the approved NIVO+IPI dose. These results support the continued use of the currently approved NIVO+IPI combination dosing schedule for patients with aRCC. Trial registration number NCT02982954.