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Gene signatures with immune and angiogenic features were associated with objective response rate (ORR) to nivolumab plus ipilimumab among patients with metastatic clear cell renal cell carcinoma (ccRCC), according to results of a prospective study presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
“BIONIKK is the first randomized clinical trial on prospective and real-time molecular group assessment to guide therapy in front-line metastatic ccRCC,” Yann-Alexandre Vano, MD, PhD, of the University of Paris in France, and presenter of the study, said.
The open-label, phase 2 BIONIKK trial randomly assigned 202 patients with previously untreated metastatic ccRCC according to their gene signature score. Four different gene signatures with immune and angiogenic features were identified: ccrcc1 was immune-low, ccrcc2 was angiogenic-high, ccrcc3 was normal-like, and ccrcc4 was immune-high. Patients with ccrcc1 or 4 were assigned to nivolumab or nivolumab/ipilimumab followed by nivolumab alone; patients with ccrcc2 or 3 were assigned to nivolumab/ipilimumab followed by nivolumab alone or a tyrosine kinase inhibitor (TKI). The primary endpoint was ORR and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and tolerability.
At baseline, the median age was 62, most patients had previously undergone nephrectomy, and most patients had an Eastern Cooperative Oncology Group performance status of 0. The majority of patients had intermediate/poor risk disease.
ORR and median PFS varied across the ccrcc groups; however, the OS data were not yet mature.
In the ccrcc2 group, the ORR was 53.8% and 48.3% with TKI or nivolumab/ipilimumab, respectively. The median PFS was not reached with the TKI compared with 10.4 months with nivolumab/ipilimumab.
Patients in the ccrcc3 group achieved ORRs of 0 and 25.0% with TKI and nivolumab/ipilimumab, respectively. Median PFS was not reported for this group because the samples sizes were low (n=2 vs 4).
ORR was highest in ccrcc4 group, at 50.0% with nivolumab and 53.0% with nivolumab/ipilimumab. The median PFS was 7.8 and 12.2 months with nivolumab alone or nivolumab/ipilimumab, respectively.
For comparison, Dr Vano added that “in unselected metastatic ccRCC patients, front-line nivolumab provided a 28.7% ORR and a median PFS of 5.54 months.”
There were no new safety signals. Grade 3-4 adverse events (AEs) occurred most frequently among patients who received a TKI (55%), followed by patients in the nivolumab/ipilimumab arm (44%) and the nivolumab monotherapy arm (18%). There was 1 treatment-related death in the nivolumab/ipilimumab groups and 2 in the TKI groups.
These study results were the highest response rates ever seen with nivolumab alone in patients with ccrcc4 tumors with durable responses. Dr Vano noted that the poor prognosis of these highly infiltrated tumors seems to be reversed by the anti–PD-1. Additional biomarker analyses are ongoing.
Disclosures: Multiple authors declared affiliations with industry. Please refer to the original abstract for a full list of disclosures.
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Vano Y, Elaidi RT, Bennamoun M, et al. Results from the phase II biomarker driven trial with nivolumab (N) and ipilimumab or VEGFR tyrosine kinase inhibitor (TKI) in naïve metastatic kidney cancer (m-ccRCC) patients (pts): The BIONIKK trial. Presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract LBA25.