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Nivolumab induced responses in melanoma refractory or naive to ipilimumab
Patients with ipilimumab-refractory or ipilimumab-naive melanoma demonstrated response to nivolumab with or without a peptide vaccine, according to study results.
Researchers evaluated nivolumab (BMS-936558, Bristol-Myers Squibb) response in 90 patients with unresectable stage III or IV melanoma. The analysis included 56 patients who experienced progression after treatment with ipilimumab (Yervoy, Bristol-Myers Squibb) and 34 ipilimumab-naive patients who experienced disease progression after other prior treatment.
Patients received nivolumab in doses of 1 mg/kg, 3 mg/kg or 10 mg/kg with or without a multi-peptide vaccine.
Median follow-up was 20.3 months for patients who were ipilimumab naive and 6.8 months for patients with ipilimumab-refractory melanoma.
Of patients who were ipilimumab naive, two (6%) had complete response, six (18%) had partial response and seven (21%) had stable disease at 24 weeks. Nineteen patients (55%) experienced disease progression. The disease control rate was 45%.
Fifty-three patients with ipilimumab-refractory melanoma were evaluable for response. Of them, 14 (26%) had partial response and 11 (21%) had stable disease. Twenty-eight (53%) patients experienced disease progression. The disease control rate was 47%.
Median duration of response was not reached in ipilimumab-naive responders (range, 24 to 140+ weeks) or ipilimumab-refractory responders (range, 12+ to 60+ weeks).
The treatment appeared well tolerated, according to researchers. The most common adverse events were fatigue and injection site reaction.
Results of additional biomarker analyses showed the overall response rate for patients with positive PD-L1 membranous staining (>5%) was higher than for those with negative staining (67% vs. 19%).
Responders and patients with stable disease (P<.001) had significantly lower NY-ESO-1 and MART-1-specific CD8+ T cells at baseline than nonresponders (P<.003).
“In patients with ipilimumab-refractory or-naive melanoma, nivolumab at 3 mg/kg with or without peptide vaccine was well tolerated and induced responses lasting up to 140 weeks,” the researchers wrote. “Responses to nivolumab in ipilimumab-refractory patients or to ipilimumab in nivolumab-refectory patients support combination or sequencing of nivolumab and ipilimumab.”
Disclosure: The researchers report employment, leadership, consultant or advisory roles with, stock ownership in, and honoraria or research funding from Bristol-Myers Squibb, Genentech and Merck.
Perspective
Back to TopThe authors report the interesting results of a phase 1 trial with the use of nivolumab, a PD-1 antibody, with or without a peptide vaccine in 90 patients with advanced melanoma. Noteworthy clinical findings from the trial include a robust 25% response rate with no apparent difference between patients who were ipilimumab-naive or refractory, and a median duration of response that was not yet reached at 8.1 months of follow-up. The addition of peptide vaccine did not appear to have either a beneficial or detrimental effect, once again indicating the lack of utility of this combined approach in melanoma, similar to results with ipilimumab with or without a peptide vaccine.
Of further interest was the association between high pretreatment NY-ESO and MART-1 specific CD8+ T cells and the presence of increased T-regulatory cells at week 12 with disease progression. Although PDL-1 tumor staining was associated with responses to nivolumab, the absence of this staining did not rule out a response, data that are similar to other trials attempting to use this as a pretreatment biomarker.
This important trial adds to the accumulating data indicating the efficacy — both in terms of response rates and durability — of the PD-1 antibodies in the immunotherapy of advanced melanoma. The search for a clear-cut predictive biomarker for response remains elusive. The results of ongoing randomized trials with nivolumab and other PD-1 antibodies with or without ipilimumab in advanced melanoma are awaited with great interest and have the potential to change the landscape for this disease.