Abstract 506TiP
Background
Pembrolizumab, a PD-1 inhibitor, is now recommended as a 1L treatment for patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) unresectable or mCRC. However, treatment options are needed for patients with non-MSI-H or MMR proficient (pMMR) mCRC. Pembrolizumab + lenvatinib, a multikinase inhibitor, showed antitumor activity and had manageable safety in patients with previously treated non-MSI-H/pMMR CRC in the phase II LEAP-005 (NCT03797326) study. LEAP-017 (NCT04776148) is designed to compare the efficacy and safety of pembrolizumab + lenvatinib vs standard of care in patients with non-MSI-H/dMMR mCRC that has progressed on or after prior treatment or disease that has become intolerant to prior treatment.
Trial design
Eligibility criteria include age ≥18 y, histologically/cytologically confirmed non-MSI-H/dMMR, unresectable or metastatic Stage IV (AJCC 8th edition) mCRC, ECOG performance status 0 or 1, and provision of a baseline tumor sample. Patients will be randomly assigned 1:1 to pembrolizumab 400 mg IV Q6W + lenvatinib 20 mg PO QD or investigator’s choice (selected before randomization) of regorafenib 160 mg QD (d 1-21, no dose on d 22-28) Q4W or TAS-102 (trifluridine + tipiracil hydrochloride) 35 mg/m2 Q4W (BID on d 1-5 and d 8-12, no doses on d 6-7 or d 13-28). Randomization will be stratified by absence/presence of liver metastases. Pembrolizumab will continue for up to ∼2 y; lenvatinib may continue beyond 2 y in cases of clinical benefit, until progression, unacceptable toxicity, or investigator/patient decision. The primary end point is OS. Secondary end points are PFS, ORR, and DOR per RECIST v1.1 by blinded independent central review, safety and tolerability (AEs per NCI CTCAE v5.0), and change from baseline scores and time to deterioration in global health status/quality of life, physical functioning, appetite loss, and bloating (EORTC QLQ-C30 and EORTC QLQ-CR29). Exploratory end points include health utilities (EQ-5D-5L). Approximately 434 patients will be enrolled.
Clinical trial identification
NCT04776148; EudraCT, 2020-004289-20.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Jennifer M. Kulak, PhD, and Doyel Mitra, PhD, CMPP, of ApotheCom (Yardley, PA, USA).
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA.
Disclosure
T. Yoshino: Financial Interests, Personal, Invited Speaker: Taiho; Chugai; Eli Lilly; Merc Biopharma; Bayer; Ono; Financial Interests, Institutional, Invited Speaker: MSD; Ono; Sanofi; Daiichi Sankyo; Sumitomo Dainippon; Chugai; Parexel International; Financial Interests, Institutional, Research Grant: Taiho; MSD; Ono; Amgen. R. Fu: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck Sharp & Dohme Corp.,a subsidiary of Merck & Co., Inc..N. Hawk: Financial Interests, Personal, Full or part-time Employment: Eisai Inc..D.E. Adelberg: Financial Interests, Personal and Institutional, Full or part-time Employment: Merck Research Laboratories/MSD. K.G. Norwood: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc..V. Heinemann: Financial Interests, Personal, Other, Honoraria: Merck; Amgen; Roche; Sanofi; SIRTEX; Servier; Pfizer; Pierre-Fabre; AstraZeneca; MSD; Financial Interests, Personal, Advisory Board: Merck; Amgen; Roche; Sanofi; SIRTEX; BMS; MSD; Novartis; Boehringer Ingelheim; Servier; Pierre-Fabre; Celgene; Terumo; Merck; Amgen; Roche; Sanofi; Pfizer; Boehringer-Ingelheim; SIRTEX; Bayer; Servier; Financial Interests, Personal, Other, Travel expenses, including accommodations: Merck; Roche; Amgen; SIRTEX; Bayer; Servier.