Immunotherapy Combination in Metastatic RCC Proves Effective

Patients with metastatic renal cell carcinoma (RCC) had durable responses and manageable safety when treated with the combination of the immune checkpoint inhibitors nivolumab and ipilimumab, according to the results of the CheckMate 016 study published in the Journal of Clinical Oncology. Treatment with the combination resulted in an objective response rate (ORR) of about 40%.

Hans J. Hammers, MD, PhD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues wrote that this study “provides preliminary support for the robust clinical activity of nivolumab plus ipilimumab combination therapy as evidenced by improved ORR relative to nivolumab monotherapy previously reported in phase II and phase III metastatic RCC studies.”

CheckMate 016 was designed to evaluate the combination of nivolumab and ipilimumab and the combination of nivolumab plus a tyrosine kinase inhibitor in patients with metastatic RCC. These published results included safety and efficacy data from the nivolumab plus ipilimumab arms of CheckMate 016.

Patients enrolled in the study received 3-mg/kg nivolumab plus 1-mg/kg ipilimumab (N3I1), 1-mg/kg nivolumab plus 3-mg/kg ipilimumab (N1I3), or 3-mg/kg nivolumab plus 3-mg/kg ipilimumab (N3I3) every 3 weeks for 4 doses followed by 3-mg/kg nivolumab monotherapy every 2 weeks until progression or toxicity.

Patients assigned to N3I3 were censored due to dose-limiting toxicity or other reasons. Among the patients in the N3I1 and N1I3 arms, the confirmed ORR was 40.4% at a median follow-up of 22.3 months.

The researchers noted that previous studies of nivolumab monotherapy in this patient population reported ORRs of 20% and 25%. Studies of ipilimumab monotherapy reported responses of 5% and 12.5%. Therefore, the higher ORR seen here “suggests that nivolumab plus ipilimumab combination therapy offers improved activity over nivolumab monotherapy in this setting.”

In the N3I1 arm, 10.6% of patients achieved a complete response and 29.8% achieved a partial response. There were no complete responses in the N1I3 arm, but 40.4% of patients had a partial response. Ongoing responses were seen in 42.1% of patients in the N3I1 arm and 36.8% of patients in the N1I3 arm. The 2-year overall survival rate was 67.3% in the N3I1 arm and 69.6% in the N1I3 arm.

“Although the N3I1 and N1I3 combination therapies were similarly efficacious, the overall safety results support additional clinical development of N3I1,” the researchers wrote.

All patients on both arms experienced an adverse event of any grade, and 71.3% experienced a grade 3 or worse adverse event. Treatment-related adverse events occurred in 93.6% of all patients. Patients assigned to the N1I3 arm had a higher rate of grade 3/4 treatment-related adverse events compared with the N3I1 arm (61.7% vs 38.3%). Fewer patients in the N3I1 arm discontinued treatment due to treatment-related adverse events.

“The preliminary efficacy results of the N1I3 and N3I1 arms along with the encouraging safety results in patients treated with the N3I1 combination regimen support the additional clinical investigation of N3I1 in a phase III study for patients with metastatic RCC,” the researchers concluded.