medwireNews: Initial results from the Fast Real-Time Assessment of Combination Therapies in Immuno-Oncology (FRACTION) trial suggest that some patients with advanced renal cell carcinoma (RCC) may benefit from nivolumab plus ipilimumab after immune checkpoint inhibitor (ICI) therapy.
The phase 2 study findings were reported at the virtual 2020 ASCO Annual Meeting by Toni Choueiri, from the Dana-Farber Cancer Institute in Boston, Massachusetts, USA, who explained that the trial is part of a program designed to “expedite the selection of optimal [immuno-oncology] combinations to address the unmet need for effective treatment options.”
Track 2 of FRACTION-RCC was designed to determine whether nivolumab plus ipilimumab could play a role in the treatment of advanced clear-cell RCC patients who had progressed on first-line PD-1, PD-L1, or CTLA-4 inhibitor therapy.
This cohort included 46 patients who were given four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg at 3-week intervals, followed by nivolumab 480 mg every month for up to 2 years, with patients who progressed eligible for re-randomization to alternative FRACTION regimens.
The median duration of treatment was 3 months at time of reporting, with six patients continuing the regimen, Choueiri reported.
After a median of 21.6 months, the primary outcome of overall response rate was 15.2%, made up of seven patients with a partial response. The disease control rate, which included patients with stable disease, was 52.2%.
In addition, 37% of the 46 patients showed tumor reduction in a waterfall plot analysis and median progression-free survival was 16.1 weeks.
On closer analysis, the seven patients who achieved partial responses had been given between one and eight prior therapies, including nivolumab alone or with an anti-LAG-3 antibody, or avelumab plus axitinib. But just one had achieved a partial response and two stable disease with these regimens, while five patients progressed within 3 months of the most recent ICI treatment.
Treatment-related adverse events (TRAEs) of any grade occurred in 78% of patients, most commonly rash (20%), fatigue (20%), diarrhea (17%), nausea (15%), and pruritus (13%). Grade 3–4 TRAEs were reported for 28% of patients, most commonly diarrhea (9%) and elevated amylase (7%), while 9% had a serious TRAE and 7% discontinued treatment because of side effects. There were no treatment-related deaths.
Rash was the most common immune-mediated TRAE of any grade, affecting 26% of patients, followed by diarrhea or colitis (17%), with the latter affecting 11% of patients at grade 3–4. Rash and hepatitis at grade 3–4 were experienced by 2% of patients each.
The safety profile of nivolumab plus ipilimumab was “manageable,” the presenter said, noting that 13% of patients were given prednisone at a dose of 40 mg/day or more for immune-mediated events.
“While the efficacy of [nivolumab–ipilimumab] after checkpoint inhibitor-based therapy observed here was not as robust as seen in treatment-naïve patients in the CheckMate 214 trial, these results help inform a data gap concerning the use of [nivolumab–ipilimumab] after previous [immuno-oncology] treatment,” Choueiri concluded.
He added: “The FRACTION-RCC trial offers, overall, a novel, efficient strategy for assessing [immuno-oncology] therapies to provide new treatment options for advanced RCC patients with high unmet medical needs.”
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This independent news story was supported by an educational grant from Pfizer and Merck KGaA