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

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

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-LA...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:BJC Reports
Online Access:https://doi.org/10.1038/s44276-024-00118-x
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Summary: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. Clinical trial registration NCT03250832.
ISSN:2731-9377

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