O3-1-1Combined Safety Analysis for Japanese in Domestic Phase 1, Phase 1b and International Phase 2/3 Trials of Pembrolizumab

Some anticancer drugs have different safety profiles by race, such as myelo-suppression and interstitial lung disease. There is a clinical need to confirm the safety profile of anti-PD1 drugs for Japanese patients. The dataset for this combined analysis included Japanese patients who participated in a Japanese phase 1 trial for solid tumors (KEYNOTE-011 part A), a Japanese phase 1b trial for non-small cell lung cancer (NSCLC) (KEYNOTE-025), an international phase 2/3 for NSCLC (KEYNOTE-010) and a Japanese phase 1b trial for melanoma (KEYNOTE-041). We analyzed the incidence of adverse events among patients who received at least one cycle of pembrolizumab. The numbers of Japanese patients who received pembrolizumab monotherapy were 10 in KEYNOTE-011 part A, 38 in KEYNOTE-025, 62 in KEYNOTE-010, and 42 in KEYNOTE-041, including 105 NSCLC and 45 melanoma patients. Among the total of 152 Japanese patients, any drug-related adverse events occurred in 127 (84%) patients, whereas Grade > =3 drug-related adverse events in 31 (20%) patients and drug-related deaths in 3 (0.2%) patients were observed. Among the total of 2799 patients from 4 global trials for melanoma or NSCLC (KEYNOTE-001, 002, 006, 010), any drug-related adverse events occurred in 2727 (97.4%) patients, whereas Grade > =3 drug-related adverse events occurred in 386 (13.8%) patients and drug-related deaths were observed in 10 (0.4%) patients. In overall population and Japanese patients who received pembrolizumab in KEYNOTE-010, Grade > =3 drug-related adverse events occurred in 98 (14%) and 14 (22%) patients, any immune-mediated adverse events occurred in 133 (20%) and 15 (24%), Grade > =3 immune-mediated adverse events occurred in 36 (5.3%) and 8 (13%), and pneumonitis in 31 (4.5%) and 3 (4.8%) patients, respectively. The safety profile of pembrolizumab in Japanese patients did not show clinically meaningful differences compared to non-Japanese patients.