A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151)

Lu Si, Xiaoshi Zhang, Yongqian Shu, Hongming Pan, Di Wu, Jiwei Liu, Fang Lou, Lili Mao, Xuan Wang, Xizhi Wen, Yanhong Gu, Lingjun Zhu, Shijie Lan, Xin Cai, Scott J Diede, Yu Zhou, Jun Ge, Jianfeng Li, Haiyan Wu, Jun Guo, Lu Si, Xiaoshi Zhang, Yongqian Shu, Hongming Pan, Di Wu, Jiwei Liu, Fang Lou, Lili Mao, Xuan Wang, Xizhi Wen, Yanhong Gu, Lingjun Zhu, Shijie Lan, Xin Cai, Scott J Diede, Yu Zhou, Jun Ge, Jianfeng Li, Haiyan Wu, Jun Guo

Abstract

Background: Pembrolizumab shows robust antitumor activity and favorable safety in metastatic melanoma. KEYNOTE-151 evaluated pembrolizumab in Chinese patients, who have more aggressive melanoma subtypes than other populations.

Methods: Chinese patients aged ≥18years with advanced melanoma previously treated with one line of therapy received pembrolizumab 2 mg/kg every 3 weeks for 35 cycles or until confirmed disease progression, intolerable toxicity, or study withdrawal. Primary end points were objective response rate (ORR) per RECIST v1.1 by blinded independent central review and safety. Key secondary end points included duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 and overall survival (OS).

Results: Median age was 52 years (N=103); 37.9% had acral and 14.6% had mucosal melanoma. Median follow-up was 7.9months at data cutoff (December 27, 2017). ORR was 16.7% (95% CI, 10.0-25.3%) (1 complete, 16 partial responses). Disease control rate was 38.2%. ORR was 15.8% for acral, 13.3% for mucosal melanoma. Median DOR was 8.4months; 65.6% of patients had response duration ≥6months. Median PFS was 2.8months (95% CI, 2.7-3.5months); 6-month rate was 20.4%. Median OS was 12.1months (95% CI, 9.6months-not reached); 6-month rate, 75.7%; 12-month rate, 50.6%. Treatment-related AEs (TRAEs) occurred in 87 (84.5%) patients; 9 (8.7%) experienced grade 3/4 TRAE and 2 (1.9%) discontinued because of TRAE; none died. Two deaths occurred that were unrelated to treatment.

Conclusions: Pembrolizumab was well tolerated and provided clinically meaningful antitumor activity as second-line therapy in Chinese patients with advanced melanoma.

Copyright © 2019. Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
Duration of response based on RECIST v1.1 per BICR. BICR, blinded independent central review; PD, progressive disease; PR, partial response; Q3W, every 3 weeks; RECIST, Response Evaluation Criteria in Solid Tumors.
Fig. 2
Fig. 2
Best percentage change in target lesion size from baseline based on RECIST v1.1 per BICR in the full-analysis set. Values ≥100 were set to 100. Data were not available for 13 patients (12.7%). BICR, blinded independent central review; Q3W, every 3 weeks; RECIST, Response Evaluation Criteria in Solid Tumors.
Fig. 3
Fig. 3
Kaplan–Meier estimates of PFS (A) in the full-analysis set per BICR and OS (B) in all-patients-as-treated population. BICR, blinded independent central review; OS, overall survival; PFS, progression-free survival; Q3W, every 3 weeks.

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