CITRINO: phase 1 dose escalation study of anti-LAG-3 antibody encelimab alone or in combination with anti-PD-1 dostarlimab in patients with advanced/metastatic solid tumours.
J Randolph Hecht, Jean-Marie Michot, David Bajor, Amita Patnaik, Ki Y Chung, Judy Wang, Gerald Falchook, James M Cleary, Richard Kim, Anuradha Krishnamurthy, Omkar Marathe, Hagop Youssoufian, Catherine Ellis, Angela Waszak, Srimoyee Ghosh, Hailei Zhang, Kaitlin Yablonski, Shruti D Shah, Ivan Diaz-Padilla, Susanna Ulahannan
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引用次数: 0
Abstract
Background: Dual programmed cell death protein (ligand)-1 (PD-[L]1) and lymphocyte-activation gene-3 (LAG-3) blockade has demonstrated improved anti-tumour response in some advanced solid tumours. CITRINO, a two-part, Phase 1 dose-escalation study, evaluated encelimab (TSR-033; novel anti-LAG-3) monotherapy and in combination in patients with advanced/metastatic solid tumours.
Methods: Part 1 (P1) involved dose escalation (20-720 mg Q2W) of encelimab as monotherapy (P1A/B) and with dostarlimab (500 mg Q3W) in patients with previously treated advanced/metastatic solid tumours (P1C). P2 involved cohort expansion in patients with anti-PD-(L)1-naïve microsatellite stable advanced/metastatic colorectal cancer with recommended phase 2 dose (RP2D) of encelimab with dostarlimab as third/fourth-line therapy (P2A), or with dostarlimab, bevacizumab and mFOLFOX6/FOLFIRI as second-line therapy (P2B). Objectives included RP2D, safety/tolerability, efficacy, pharmacokinetics/pharmacodynamics, and exploratory biomarkers.
Results: Maximum tolerated encelimab dose was not reached; 720 mg Q2W was used for P2 plus dostarlimab 1000 mg Q6W. One dose-limiting toxicity occurred (Grade 2 myasthenia gravis; P1A). No clinical responses were observed in P1; 1 (3%) and 4 (17%) patients achieved partial response in P2A and 2B, respectively.
Conclusions: Encelimab has a manageable safety profile as a monotherapy and in tested combinations; however, anti-tumour activity was limited.
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