There was no efficacy benefit for modified dosing of nivolumab plus ipilimumab in a community-based phase 3b/4 trial among patients with advanced renal cell carcinoma (RCC), according to a poster presented at the virtual 19th International Kidney Cancer symposium.

The current approved dosing for nivolumab plus ipilimumab for advanced RCC is based on the CheckMate 214 trial. The purpose of the phase 3b/4 CheckMate 920 trial was to evaluate a modified dosing scheme among patients with predominantly clear cell RCC, in cohort 1 of the trial, and standard dosing among patients with characteristics that were excluded from the original phase 3 trial in cohorts 2 to 4.

The CheckMate 920 trial was an open-label, nonrandomized study in which 200 patients with previously untreated advanced or metastatic RCC of any risk group were assigned to 4 different cohorts. Cohort 1 included patients with predominantly clear cell histology and a Karnofsky performance status (KPS) of at least 70% who received 6 mg/kg of nivolumab plus 1 mg/kg of ipilimumab every 8 weeks, alternating with nivolumab 480 mg every 8 weeks; the altered dosing was staggered every 4 weeks for up to 2 years or until disease progression, unacceptable toxicity, or withdrawal of consent. This presentation included the results of the cohort 1.

The remaining cohorts 2 through 4 were treated with 3 mg/kg of nivolumab plus 1 mg/kg of ipilimumab every 3 weeks for 4 doses, followed by 480 mg of nivolumab every 4 weeks for up to 2 years or until disease progression, unacceptable toxicity, or withdrawal of consent. Cohort 2 included patients with non–clear cell histology and a KPS of at least 70%, cohort 3 included patients with any histology and nonactive brain metastases with a KPS of at least 70%, and cohort 4 included patients with any histology with a KPS of 50% to 60%.


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The primary endpoint was all-cause grade 3 or higher immune-related adverse events (irAEs) within 100 days of the last dose. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and overall survival (OS).

Among the 106 patients treated in cohort 1, the median age was 64.5 years, and 81% were male. The majority of patients had intermediate-risk disease (61.3%), followed by favorable-risk disease (19.8%), and poor-risk disease (18.9%). Most patients did not have sarcomatoid features (87.7%).

Treatment discontinuation due to study drug toxicity occurred among 18.9% of patients. The most common grade 3 or higher irAEs were diarrhea/colitis (7.5%), rash (4.7%), hepatitis (2.8%), and adrenal insufficiency (1.9%). There were no grade 5 irAEs. Corticosteroid treatment of at least 40 mg of prednisone or the equivalent was required among 36.8% of patients.

The most common grade 3 or higher treatment-related AEs included elevated lipase, elevated amylase, fatigue, diarrhea, and nausea.

ORR was 34.4% with a median DOR of 9.2 months. The median PFS was 4.8 months, with 28.7% and 15.9% at 12 and 24 months, respectively. Median OS was not yet reached; the rate of OS at 12 months was 78.1% and 62.2% at 24 months.

“With similar follow-up, efficacy measures with modified nivolumab plus ipilimumab dosing in CheckMate 920 showed no evidence of improvement relative to those seen with standard combination dosing in CheckMate 214,” Johanna C. Bendell, MD, of Tennessee Oncology in Nashville, and presenter of the study, said. She did caution, however, that direct comparisons could not be made due to differences in study designs.

As a result of this study, Dr Bendell concluded that “the observed antitumor activity reinforces continued use of the standard combination dosing.”

Reference

Bendell JC, Hutson T, Gordan L, et al. Nivolumab 6 mg/kg plus ipilimumab 1 mg/kg (N6I1) every 8 weeks (Q8W) alternating with nivolumab 480 mg Q8W for first-line (1L) advanced renal cell carcinoma (aRCC): safety and efficacy from CheckMate 920. Presented at: 19th Annual Meeting of the International Kidney Cancer Symposium (IKCS 2020); November 6-7, 2020. Abstract CTR143.

This article originally appeared on Cancer Therapy Advisor