KEYNOTE-025: Phase 1b study of pembrolizumab (pembro) in Japanese patients (pts) with previously treated PD-L1+ non-small cell lung cancer (NSCLC)

Background

Pembro is a potent, highly selective humanized monoclonal antibody against PD-1. We present preliminary safety and efficacy results for Japanese pts in KEYNOTE-025 (NCT02007070).

Methods

Pts had measurable disease, ECOG performance status of 0 or 1, and adequate organ function. Prior therapy with ≥1 platinum-doublet chemotherapy regimen was required; an appropriate tyrosine kinase inhibitor was required for pts with sensitizing EGFR mutations (mut) or ALK translocations. All pts had PD-L1+ tumors, defined as staining in ≥1% of tumor cells as determined by a clinical trial IHC assay using the 22C3 antibody. Pembro 10 mg/kg was given every 3 weeks for up to 2 years, until disease progression or unacceptable toxicity. Primary endpoints were safety, tolerability, and overall response rate (ORR) per RECIST v1.1 by central review. Chest CT images were assessed for diagnosis of interstitial lung disease (ILD) by an independent radiologist.

Results

38 pts were treated with pembro. Median (range) age was 66.0 (41-78) years; 68.4% were Male; 26.3% were EGFR mut. 60.5% received ≥2 prior therapies. Most common drug-related adverse events (AEs) include malaise (n = 8), diarrhea (n = 6), AST increased, decreased appetite, pruritus, rash, maculopapular rash (n = 5 each). 21.1% experienced grade 3-5 drug-related AEs. ILD was observed in 4 pts (3 grade 2, 1 grade 5). In the 37 pts with measurable disease at baseline, ORR was 18.9% (95% CI, 8.0-35.2). At the time of analysis (median follow-up, 11.5 months), 85.7% responses were ongoing, and the median response duration was not reached (range, 9.1+ to 46.1+ months). Median progression-free survival (PFS) was 3.8 months (95% CI, 2.0-6.2), and 6-mo PFS and 1-year overall survival (OS) rates were 38.8% and 51.0%, respectively. In the 11 pts who had PD-L1 expression in ≥ 50% of tumor cells, ORR was 27.3% (95% CI, 6.0-61.0). Median PFS was 4.1 months (95% CI, 1.6-NR), and 6-month PFS and 1-year OS rates were 41.7% and 56.3%, respectively.

Conclusions

Pembro was generally well tolerated in Japanese pts, but ILD should be carefully monitored. Pembro showed promising anti-tumor efficacy in Japanese pts with previous treated PD-L1+ NSCLC.

Clinical trial identification

NCT02007070

Legal entity responsible for the study

MSD K.K.

Funding

MSD K.K.

Disclosure

T. Kato: Research fund: MSD. T. Takahashi: Grants from MSD K.K., grants and personal fees from Eli Lilly Japan K.K., grants and personal fees from Chugai, grants and personal fees from ONO, personal fees from AstraZeneca K.K., outside the submitted work. H. Yoshioka: Honoraia from Chugai pharmaceuticals and Ono pharmaceuticals. K. Nakagawa: Ono Pharmaceutical Co., Ltd. / AstraZeneca K.K. / Chugai Pharmaceutical Co., Ltd. for honoraria. MSD K.K. /Ono Pharmaceutical Co., Ltd. / Chugai Pharmaceutical Co., Ltd. for research funding. M. Maemondo: Lecture fee from AstraZeneca, Chugai, Pfizer, and Lilley. Conducting a clinical study supported by Chugai. T. Seto: Honoraria or research funds for Astellas, AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Kyowa Hakko Kirin, Merck Serono, MSD, Nippon Boehringer Ingelheim, Nippon Kayaku, Novartis Pharma, Ono, Pfizer, Sanofi, Taiho, Verastem, Yakult. K. Kasahara: AstraZeneca, Parexel, Quitales, MSD, Pfizer, BMS. M. Satouchi: Research Funding, Honoraria; MSD. K. Noguchi, T. Shimamoto: Employee of MSD K.K. M. Nishio: Honoraria: Pfizer, BMS, ONO, Chugai, Lilly, TAIHO, AstraZeneca. Consulting or Advisory role: Novartis, ONO, Chugai, Lilly, TAIHO, Pfizer, Daiichi Sankyo. Research funding: Novartis, ONO, Chugai, BMS, TAIHO, Eli Lilly, Pfizer, Astellas, AstraZeneca. All other authors have declared no conflicts of interest.