Abstract
MK-3475 has shown durable antitumor activity in melanoma
across multiple doses and schedules. We compared the efficacy
and safety of two MK-3475 doses in patients with melanoma
(study sponsored by Merck Sharp & Dohme Corp.). In sepa-
rate cohorts, ipilimumab-naive (IPI-N) and ipilimumab-refrac-
tory (IPI-R) patients were randomized 1: 1 to MK-3475 2 or
10 mg kg¯¹ every 3 weeks (2 Q3W or 10 Q3W). IPI-N
patients received ≤ 2 prior systemic therapies. IPI-R patients
had any number of prior therapies and unequivocal or con-
firmed progressive disease per immune-related response crite-
ria (irRC) after ≥ 2 IPI doses; all BRAF-mutant patients were
previously treated with BRAF inhibitors. The primary endpoint
was overall response rate (ORR) assessed by RECIST 1.1 every
12 weeks by independent central review. Investigator-assessed
response by irRC was also obtained. A total of 103 IPI-N (2
Q3W, n = 51; 10 Q3W, n = 52) and 173 IPI-R (2 Q3W,
n = 89; 10 Q3W, n = 84) patients were randomized. In both
cohorts, treatment arms were well balanced for known prog-
nostic factors. As of the 18 October 2013 cut-off, all IPI-N
and 47% of IPI-R patients had ≥ 9 months of follow-up.
Among evaluable IPI-N patients, no significant between-dose
differences were observed for ORR by RECIST (33% with 2
Q3W vs. 40% with 10 Q3W; P = 0.4835) or irRC (39% vs.
40%; P = 0.9040). There were also no between-dose differ-
ences in IPI-R patients (RECIST 26% vs. 26%; P = 0.9558;
irRC 27% vs. 32%; P = 0.4568). Response duration ranged
from 6+ to 39+ weeks by RECIST (4+ to 42+ weeks by irRC)
in both cohorts (median not reached), with ~90% of
responses ongoing. Median progression-free survival (PFS)
was similar between doses in IPI-N (27 vs. 23 weeks by RE-
CIST; 36 vs. 26 weeks by irRC) and IPI-R (22 vs. 14 weeks
by RECIST; 31 vs. 25 weeks by irRC) patients. In IPI-N
patients, 24-week PFS rates were 51% vs. 48% by RECIST and
60% vs. 50% by irRC. In IPI-R patients, 24-week PFS rates
were 45% vs. 37% by RECIST and 57% vs. 57% by irRC. The
safety profile was generally similar between patients treated
with 2 Q3W and 10 Q3W. There were no drug-related
deaths. In summary, MK-3475 2 mg kg¯¹ Q3W and
10 mg kg¯¹ Q3W provided similar efficacy and safety in both
IPI-N and IPI-R patients. Treatment was well tolerated with an
acceptable toxicity profile. The high ORR provided by
MK-3475 comes with long durability in both IPI-N and IPI-R
melanoma.
Original language | English |
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Article number | 097 |
Pages (from-to) | e56 |
Number of pages | 1 |
Journal | British Journal of Dermatology |
Volume | 171 |
Issue number | 3 |
Publication status | Published - 19 Sep 2014 |
Externally published | Yes |
Event | 15th World Congress on Cancers of the Skin - Edinburgh, United Kingdom Duration: 3 Sep 2014 → 6 Sep 2014 |