CHICAGO — Combined treatment with pembrolizumab and ipilimumab demonstrated robust antitumor activity and acceptable toxicity in patients with advanced melanoma, according to data from the KEYNOTE-029 trial presented at the ASCO Annual Meeting.
The anti–PD-1 antibody pembrolizumab (Keytruda, Merck) is approved in the United States and internationally for the treatment of advanced melanoma. Data from the KEYNOTE-006 trial showed pembrolizumab conferred superior OS over ipilimumab (Yervoy, Bristol-Myers Squibb).
Georgina V. Long
A prior phase 3 trial demonstrated that pembrolizumab, in combination with ipilimumab or nivolumab (Opdivo, Bristol-Myers Squibb), extended PFS and produced a higher overall response rate than any checkpoint inhibitor alone, although toxicity also increased with the combinations.
Preliminary results from the phase 1 KEYNOTE-029 study suggested that standard-dose pembrolizumab and reduced-dose ipilimumab induced robust responses and appeared safe.
Georgina V. Long, BSc, PhD, MBBS, FRACP, chief of melanoma medical oncology and translational research at University of Sydney and clinical researcher at Melanoma Institute Australia, presented data from the expansion cohort of the study.
The expansion cohort included data from 153 patients (median age, 60 years; range, 22-82; 66% men) with advanced melanoma and no brain metastases. None of the patients received prior immunotherapy.
The researchers assigned patients to four doses of pembrolizumab (2 mg/kg) and ipilimumab (1 mg/kg) every 3 weeks, followed by pembrolizumab monotherapy every 3 weeks for up to 2 years, or until progression or intolerable toxicity.
Safety served as the primary endpoint. Secondary endpoints included ORR, OS, PFS and duration of response.
Median follow-up was 10 months (range, 0.8-14.1).
Seventy-two percent of patients (n = 110) received all four doses of ipilimumab, and 56% (n = 86) remained on pembrolizumab at the time of reporting. Forty-four percent of patients (n = 67) have discontinued all treatment.
Reasons for therapy cessation included adverse events (n = 31), disease progression (n = 29), complete response (n = 3), patient withdrawal (n = 2), death (n = 1) or change in therapy (n = 1).
Ninety-five percent (n = 145) of the cohort experienced an adverse event, with 58% (n = 89) experiencing an immune-mediated adverse event. The most common treatment-related adverse events included fatigue (any grade, 46%), pruritus (any grade, 39%), rash (any grade, 39%; grade 3-4, 3%) diarrhea (any grade, 24%; grade 3-4, < 1%), lipase increase (any grade, 18%; grade 3-4, 14%) and vitiligo (any grade, 18%).
Common immune-mediated adverse events included hypothyroidism, hyperthyroidism, hypophysitis, pneumonitis, hepatitis and colitis.
The cohort had an ORR of 57% (95% CI, 49-65) and a disease control rate of 78% (95% CI, 71-85). Fifteen patients (10%) achieved a complete response as best overall response, and 72 patients (47%) achieved a partial response. Thirty-three patients (22%) achieved stable disease and 30 patients (20%) experienced disease progression.
All but two of the 87 responding patients maintained their responses at the time of data cutoff, with response duration ranging from greater than 6 weeks to greater than 43 weeks.
Median PFS and OS have not been reached. Seventy percent of patients were progression free at 6 months, Long said. – by Cameron Kelsall
Long GV, et al. Abstract 9506. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Disclosure: Merck funded this study. Long reports honoraria from and/or consultant roles with Amgen, Bristol-Myers Squibb, Merck, Novartis, Provectus and Roche. Please see the abstract for a list of all other researchers’ relevant financial disclosures.