Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041)

Abstract

PurposeThis phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma.MethodsPembrolizumab (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed progression or unacceptable toxicity. The tumor response was assessed as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both investigator review and central review.ResultsForty-two patients with advanced melanoma received pembrolizumab. A primary cutaneous histology was observed in 34 patients (81.0%), while a primary mucosal histology was observed in 8 patients (19.0%). Thirty-four patients (81.0%) experienced treatment-related adverse events (AEs). The most common treatment-related AEs were pruritus, maculopapular rash, malaise, and hypothyroidism. Grade 3–5 treatment-related AEs occurred in 8 patients (19.0%). The only grade 3–5 treatment-related AE reported in at least two patients was anemia. There were two treatment-related deaths (unknown cause and cerebral hemorrhage). Among the 37 evaluable patients, the confirmed overall response rates (ORRs) determined by central review were 24.1% (95% CI 10.3–43.5) for cutaneous melanoma and 25.0% (95% CI 3.2–65.1) for mucosal melanoma. The responses were durable, and the median duration of response was not reached in either population. The median overall survival (OS) was not reached, with a 12-month OS of 82.7% for cutaneous melanoma and 51.4% for mucosal melanoma.ConclusionThe safety profile of pembrolizumab in Japanese patients was similar to that reported in the previous clinical studies. Pembrolizumab provided promising anti-tumor activity in Japanese patients with advanced melanoma.

KEYNOTE‐025: Phase 1b study of pembrolizumab in Japanese patients with previously treated programmed death ligand 1–positive advanced non–small‐cell lung cancer

“…The safety profile of pembrolizumab in this study was generally similar to that reported in previous studies evaluating pembrolizumab monotherapy in patients with advanced NSCLC . The finding that pembrolizumab was well tolerated in Japanese patients is consistent with results from the KEYNOTE‐041 study, which found pembrolizumab to be well tolerated in Japanese patients with advanced melanoma . The most common treatment‐related AE in our study were malaise, diarrhea and rash.…”

Immune‐related adverse events correlate with improved survival in patients with advanced mucosal melanoma treated with nivolumab: A single‐center retrospective study in Japan

“…However, the efficacy of nivolumab monotherapy in MM was not known because of its rarity. In Japanese clinical trials of anti‐PD‐1 monotherapy for advanced melanoma, the ORR for nivolumab and pembrolizumab was 34.8% and 24.3%, respectively, whereas the DCR for nivolumab and pembrolizumab was 65.2% and 48.6%, respectively. In comparison, the ORR and DCR in MM were 30% and 56%, respectively, in the current study.…”

Three cases of nivolumab therapy‐failed advanced melanoma successfully controlled by ipilimumab with intensity‐modulated radiotherapy

“…8 Because the Japanese melanoma population possesses a high ratio of acral lentiginous melanoma and mucosal melanoma 9 with low levels of TMB, 8 the efficacy of anti-PD-1 Ab in the Japanese population is lower than that in Caucasian populations. [1][2][3] For the patients with anti-PD-1 Ab-failed advanced melanoma, ipilimumab is another choice, especially for melanoma without the BRAF gene mutation. 10 However, because the efficacy of ipilimumab in patients with nivolumab-resistant melanoma is extremely low after objective tumor progression, 5 radiotherapy is sometimes administrated in combination with ipilimumab.…”

“…Recently, anti‐programmed death 1 (PD‐1) antibody (Ab) monotherapy has been one of the first‐line therapies for the treatment of advanced melanoma, especially for BRAF mutation‐negative melanoma . However, its efficacy rate is 24.1–34.8% in the Japanese population, which is lower than that of a previous clinical trial in another country (43.7%) .…”