Combination therapy with ipilimumab and the investigational antibody nivolumab led to lasting tumor shrinkage in about half of patients with aggressive, advanced melanoma, according to results of a phase 1 study.
Jedd D. Wolchok, MD, PhD, a medical oncologist at Memorial Sloan-Kettering Cancer Center and a HemOnc Today Editorial Board member, called the complete and near-complete response rates “unprecedented” for an immunotherapy in melanoma.
Jedd D. Wolchok
Ipilimumab (Yervoy, Bristol-Myers Squibb) and nivolumab (BMS-936558, Bristol-Myers Squibb) target immune system checkpoints on immune cells, increasing the immune system’s ability to fight off cancer, according to background information provided by researchers.
For their study, Wolchok and colleagues enrolled patients with inoperable stage III and stage IV metastatic melanoma who underwent up to three prior therapies.
Some patients received concurrent treatment with the two drugs. The regimen consisted of four doses of nivolumab (dose range, 0.3-3 mg/kg) plus ipilimumab (dose range, 1-3 mg/kg) every 3 weeks for four doses, followed by nivolumab alone every 3 weeks for four doses. At week 24, patients resumed combined treatment every 12 weeks for eight doses.
The sequenced cohorts included patients previously treated with ipilimumab outside of the current trial who did not experience significant tumor shrinkage. These patients were treated with nivolumab alone every 2 weeks for 48 doses.
Different doses of nivolumab and ipilimumab were used within both cohorts.
During a press conference intended to highlight select research that will be presented at the ASCO Annual Meeting, Wolchok presented data on 86 patients.
No treatment-associated deaths have been reported in any of the treatment arms, and side effects were managed using standard medication protocols, Wolchok said.
The results indicated objective response rates of 21%, 53% and 50% in the three concurrent treatment arms. The highest response rate was observed in patients treated with nivolumab 1 mg/kg and ipilimumab 3 mg/kg, the doses being taken into later-stage trials.
“What was unique in our experience was that most of these responding patients had rapid and deep regressions,” Wolchok said.
Three out of four patients who responded to concurrent treatment demonstrated tumor reduction within 3 months, a rate faster than that observed with ipilimumab alone, Wolchok said. Sixteen of 52 patients (31%) experienced tumor shrinkage of more than 80%.
“When all concurrent cohorts were considered together, 40% had objective responses,” Wolchok said. “If one broadens this to include patients with slow responses, then 65% of patients have the melanoma controlled with this combination.”
Results from the sequenced cohorts indicated responses were noted even in patients who experienced tumor growth or disease progression during prior treatment with ipilimumab.
This suggests that when one immune modulator does not lead to response, patients may still respond to another, Wolchok said.
“My colleague, [Margaret K. Callahan, MD, PhD], will present results of a biomarker study at the upcoming ASCO meeting showing how this combination can overcome some factors which seem to hold back responses to either therapy alone,” he said. “Based on these results, a phase 3 trial will evaluate the efficacy of the concurrent nivolumab and ipilimumab combination vs. nivolumab alone vs. ipilimumab alone in patients with advanced melanoma.”
For more information:
Wolchok JD. Abstract #9012. Scheduled for presentation at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.
Disclosure: The research was supported by Bristol-Myers Squibb.