97P - Asian subgroup analysis of the phase III LEAP-017 trial of lenvatinib plus pembrolizumab vs standard-of-care in previously treated metastatic colorectal cancer (mCRC)

Background

In the global LEAP-017 trial, treatment with lenvatinib + pembrolizumab (L + P) trended toward longer, but not significant, OS (HR: 0.83, 95% CI: 0.68-1.02, p-value: 0.0379) vs regorafenib or trifluridine–tipiracil (SOC), and toward more benefit in PFS and ORR. We present results of an exploratory analysis of patients (pts) enrolled in Asia combined with an extension cohort from China.

Methods

Eligible pts were aged ≥ 18 years, with confirmed unresectable, non-MSI-H/dMMR mCRC, and ≥1 prior line of therapy. Pts were allocated (1:1) to L (20 mg QD) + P (400 mg Q6W, up to 18 cycles) or SOC. Primary endpoint was OS. Secondary endpoints were PFS and ORR per RECIST 1.1 by BICR, and safety.

Results

At data cut-off (Feb 20, 2023), 237 pts were enrolled from Asia including China (N=100), Japan (N=63), Korea (N=41), and Taiwan (N=33). Overall, 118 pts received L + P, and 117 received SOC. In the Asia subgroup, after a median follow-up of 15.1 months (mo) and 15.2 mo, respectively, OS was longer with L + P vs SOC (median 13.4 vs 10.3 mo; HR: 0.63, 95% CI: 0.45-0.88), median PFS was 3.8 mo with L + P and 3.3 mo with SOC (HR: 0.78, 95% CI, 0.58-1.05), and ORR was 11.9% (95% CI, 6.6%- 19.1%) with L + P and 0% with SOC. In the China cohort, OS was longer with L + P vs SOC (median 14.9 vs 10.3 mo; HR: 0.61, 95% CI, 0.33-1.15), median PFS was 3.7 mo with L + P and 2.4 mo with SOC (HR: 1.18, 95% CI, 0.75-1.85), and ORR was 5.7% (95% CI, 1.2%-15.7%) with L + P and 0% with SOC. Grade ≥ 3 treatment-related AE rates were 58.5% and 49.6% with L + P and SOC, respectively, in the Asia subgroup, and 43.9% and 64.3%, respectively, in the Chinese extension cohort. One grade 5 treatment-related AE of pneumonitis occurred in the L + P arm in the Asia subgroup.

Conclusions

In this exploratory analysis from the Asia subgroup of LEAP-017 including the China extension, treatment with L + P vs SOC trended toward longer OS, consistent with the global trial. Trends towards improved PFS and ORR with L + P were also seen, consistent with the global trial; however, a similar trend in the PFS HR in the China subgroup was not observed. No new safety signals were observed.

Clinical trial identification

NCT04776148; first posted on February 26, 2021.

Editorial acknowledgement

Provided by Jose Casasvonas Nieves, PhD, an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, 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

R. Xu: Financial Interests, Personal, Invited Speaker: BMS, MSD; Financial Interests, Personal, Advisory Board: Henrui, BeiGene, Astellas, Merck, Junshi. H. Teng: Financial Interests, Personal, Advisory Role: MSD Taiwan; Financial Interests, Personal, Speaker’s Bureau: MSD Taiwan. A. Takashima: Financial Interests, Institutional, Research Funding: MSD. T. Yang: Financial Interests, Institutional, Research Funding: MSD. T.W. Kim: Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Funding: Merck. T. Kim: Financial Interests, Personal, Ownership Interest: IMBdx; Financial Interests, Institutional, Research Funding: MSD. J.O. Park: Financial Interests, Personal, Advisory Board: MedPacto, BMS (Celgene), Servier, MediRama, Adicet Bio, AstraZeneca, Merck Sereno, ImmuneOncia, Merck; Financial Interests, Personal, Other, Travel support for a poster presentation at ASCO GI 2023: Minneamrita Therapeutics LLC; Financial Interests, Personal, Research Grant, Clinical research grant: MedPacto, Servier, BMS (Celgene); Financial Interests, Personal, Research Grant: Eutilex, ABL Bio. S. Lee: Financial Interests, Institutional, Research Funding: MSD. K. Yeh: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, PhytoHealth, Novartis, Ono, Merck, AstraZeneca; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology, American Association for Cancer Research. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd, Sanofi K.K., MSD K.K., Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Amgen K.K., Pfizer Japan Inc., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., Roche Diagnostics K.K., FALCO Biosystems Ltd. R. Fu, R. Jain, D.E. Adelberg: Financial Interests, Personal, Full or part-time Employment: Merck. A. Kawazoe: Financial Interests, Personal, Advisory Board: Zymeworks, Merck & Co.; Financial Interests, Personal, Invited Speaker: Taiho, Daiichi Sankyo, Eli Lilly, Bristol Myers Squibb, Ono, All other authors have declared no conflicts of interest.