47P - First-line pembrolizumab (pembro) + gemcitabine and cisplatin (gem/cis) for advanced biliary tract cancer (BTC) in the China subpopulation from the phase III KEYNOTE-966 study

Background

At the final analysis of the global phase 3 KEYNOTE-966 study (NCT04003636; N = 1069), pembro + gem/cis provided a statistically significant and clinically meaningful improvement in OS vs placebo (pbo) + gem/cis (median 12.7 vs 10.9 mo; HR 0.83; 95% CI, 0.72-0.95; P = 0.0034). Data from the prespecified China subpopulation analysis are reported.

Methods

Adults with previously untreated unresectable locally advanced or metastatic BTC were randomly assigned 1:1 to pembro 200 mg or pbo Q3W for ≤35 cycles added to gem 1000 mg/m² on days 1 and 8 Q3W until PD and cis 25 mg/m² on days 1 and 8 Q3W for ≤8 cycles. Randomization was stratified by region (Asia vs non-Asia), stage (locally advanced vs metastatic), and tumor origin (gallbladder vs intrahepatic vs extrahepatic). The primary end point was OS. Secondary end points were PFS, ORR, and DOR per RECIST v1.1 by BICR and safety. The data cutoff date was Dec 15, 2022.

Results

In China, 158 patients (pts) were randomly assigned to pembro + gem/cis (n = 75) or pbo + gem/cis (n = 83). Median time from randomization to data cutoff was 20.5 mo (range, 15.0-28.8). Efficacy is reported in the table. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 53 pts (71.6%) in the pembro + gem/cis arm vs 58 (70.7%) in the pbo + gem/cis arm; no grade 5 events occurred. Immune-mediated AEs and infusion reactions occurred in 18 (24.3%) vs 7 (8.5%) pts; most were grade 1 or 2 and manageable. Table: 47P

^aFrom product-limit (Kaplan-Meier) method

Conclusions

Consistent with the global population, pembro + gem/cis provided a numeric improvement in OS vs pbo + gem/cis in the China subpopulation; per Kaplan-Meier estimates, 49% of responders treated with pembro + gem/cis had a response lasting ≥12 months. No new safety signals were observed vs the global population. These data support pembro + gem/cis as a first-line treatment option for Chinese pts with advanced BTC.

Clinical trial identification

NCT04003636.

Editorial acknowledgement

Medical writing assistance was provided by Bresler Swanepoel, PhD, and Holly C. Cappelli, PhD, CMPP, of ApotheCom (Yardley, PA, USA).

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

Y. Pan: Financial Interests, Personal, Principal Investigator: Anhui Provincial Hospital. W. Wang: Other, Personal, Full or part-time Employment: MSD R&D China Co., Ltd. N. Li: Financial Interests, Personal, Full or part-time Employment: MSD China. U. Malhotra: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. All other authors have declared no conflicts of interest.