KEYNOTE-029: Alternate Doses of Ipilimumab Show Similar Results in Advanced Melanoma

CHICAGO-Standard-dose pembrolizumab plus ipilimumab at 50-mg and 100-mg doses showed robust, durable antitumor activity in patients with previously untreated advanced melanoma, according to the results of the KEYNOTE-029 cohort 1C (abstract 9514) presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.

Cohort 1B of the KEYNOTE-029 trial previously demonstrated that standard-dose pembrolizumab plus 4 doses of ipilimumab 1 mg/kg was more efficacious and had lower rates of grade 3–5 toxicity compared with standard-dose nivolumab plus ipilimumab in patients with advanced melanoma.

“I think we are seeing some signals [from immunotherapy in general] that we can be confident about discussing with our patients in the clinic,” said Georgina V. Long, BSc, PhD, MMBS, of the Melanoma Institute Australia, University of Sydney, and Mater and Royal North Shore Hospitals, who presented the results.

For KEYNOTE-029 cohort 1C, the investigators assessed the toxicity and antitumor activity of standard-dose pembrolizumab combined with either 50 mg or 100 mg of ipilimumab in patients with advanced melanoma. For inclusion, patients were required to have previously untreated stage III/IV melanoma, ECOG performance scores of 0 to 1, and no active central nervous system metastases. The primary endpoints were grade 3–5 treatment-related adverse event rate and objective response rate (ORR).

In total, 102 patients with a median age of 63.5 years were included (men, 70%; women, 30%). Patients were randomized to receive pembrolizumab (200 mg every 3 weeks for 24 months) plus 4 doses of ipilimumab 50 mg every 6 weeks, or pembrolizumab plus 4 doses of ipilimumab 100 mg every 12 weeks. Each arm was assigned 51 patients.

At a median follow-up of approximately 16 months, 59% of patients in the 50-mg ipilimumab arm and 47% of patients in the 100-mg ipilimumab arm remained on treatment. In the 50-mg ipilimumab arm and 100-mg ipilimumab arm, 41% and 47% of patients discontinued all treatment, respectively. The treatment-related adverse event rate for at least one event of all grades was 100% in the 50-mg ipilimumab arm and 96% in the 100-mg ipilimumab arm. The grade 3–5 treatment-related adverse event rate was 24% (10% immune-related) in the 50-mg ipilimumab arm and 39% (22% immune-related) in the 100-mg ipilimumab arm. A single patient, who was in the 50-mg ipilimumab arm, had a grade 5 event (autoimmune myocarditis).

The ORR was 55% (95% CI, 40%–69%) in the 50-mg ipilimumab arm and 61% (95% CI, 46%–74%) in the 100-mg ipilimumab arm. The disease control rate was 78% (95% CI, 65%–89%) and 86% (95% CI, 74%–94%), respectively. The median time to response was similar between the two groups (1.4 months vs 1.5 months). An ongoing response was observed in 71% of the patients in the 50-mg ipilimumab arm and 87% of patients in the 100-mg ipilimumab arm. Progression-free survival and overall survival were not yet reached.

The discussant for the study, Douglas Johnson, MD, of Vanderbilt University Medical Center, said, “We do see sustained and promising activity in this study, and there does seem to be a slight signal; although, again, very early, with more activity and toxicity with this 100-mg regimen.”