A first-in-human study of the anti-LAG-3 antibody favezelimab plus pembrolizumab in previously treated, advanced microsatellite stable colorectal cancer ☆

ESMO Open

article

E. Garralda¹  A. Sukari²  N.J. Lakhani³  A. Patnaik³  Y. Lou⁴  S.-A. Im⁵  T. Golan⁶  R. Geva⁷  M. Wermke⁸  M. de Miguel³  J. Palcza⁹  S. Jha⁹  M. Chaney⁹  A.K. Abraham⁹  J. Healy⁹  G.S. Falchook^1,10 

[1] Research Unit, Vall d’Hebron Institute of Oncology;Medical Oncology, Karmanos Cancer Institute;Clinical Research;Oncology, Mayo Clinic;Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine;Gastrointestinal Clinic, Sheba Medical Center, Tel-Aviv University;Oncology Division, Tel Aviv Sourasky Medical Center, Tel Aviv University;NCT/UCC Early Clinical Trial Unit, Technical University;Clinical Research, Merck & Co., Inc.;Drug Development, Sarah Cannon Research Institute at HealthONE

关键词: LAG-3;    PD-1;    colorectal cancer;    advanced;   

DOI  :  10.1016/j.esmoop.2022.100639

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Treatment options are limited for participants with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) that progressed after two or more prior therapies. Studies have shown that blockade of both lymphocyte-activation gene 3 (LAG-3) and programmed cell death protein 1 (PD-1) can improve antitumor activity. Here, we evaluate the antitumor activity of the LAG-3 antibody favezelimab alone or in combination with pembrolizumab in participants with MSS mCRC.Patients and methods Eligible participants with MSS PD-1/programmed death-ligand 1 (PD-L1) treatment-naive mCRC that progressed on two or more prior therapies received 800 mg favezelimab, 800 mg favezelimab plus 200 mg pembrolizumab, or 800 mg favezelimab/200 mg pembrolizumab co-formulation, every 3 weeks. The primary endpoint was safety, the secondary endpoint was objective response rate (ORR), and exploratory endpoints included duration of response, progression-free survival (PFS), and overall survival (OS).Results At the data cut-off date of 23 October 2020, a total of 20 participants received favezelimab alone, 89 received favezelimab plus pembrolizumab (including as favezelimab/pembrolizumab co-formulation); 48 had PD-L1 combined positive score (CPS) ≥1 tumors. At this interim analysis median follow-up was 5.8 months with favezelimab and 6.2 with favezelimab plus pembrolizumab. Treatment-related adverse events (TRAEs) were 65% with favezelimab and 65.2% with favezelimab plus pembrolizumab. Grade ≥3 TRAEs were 15% with favezelimab and 20% with favezelimab plus pembrolizumab. No grade 5 TRAEs occurred. Common TRAEs (≥15%) included fatigue (20.0%), nausea (15.0%) with favezelimab, and fatigue (16.9%) with favezelimab plus pembrolizumab. Confirmed ORR was 6.3% with favezelimab plus pembrolizumab, with median duration of response of 10.6 months (range 5.6-12.7 months), median OS of 8.3 months (95% confidence interval 5.5-12.9 months), and median PFS of 2.1 months (1.9-2.2 months). In an exploratory analysis of PD-L1 CPS ≥1 tumors, the confirmed ORR was 11.1%, median OS was 12.7 months (4.5 to not reached), and median PFS was 2.2 months (1.8-4.2 months) with favezelimab plus pembrolizumab.Conclusions Favezelimab with or without pembrolizumab had a manageable safety profile, with no treatment-related deaths. Promising antitumor activity was observed with combination therapy, particularly in participants with PD-L1 CPS ≥1 tumors.

【 授权许可】

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