Study of TSR-033 With an Anti-programmed Cell Death-1 Receptor (PD-1) in Participants With Advanced Solid Tumors

Summary

This is a multicenter, open-label, first-in-human Phase 1 study evaluating the anti-lymphocyte activation gene-3 (LAG-3) antibody TSR-033 alone, in combination with the anti-PD-1 antibody dostarlimab, and in combination with dostarlimab, modified folinic acid (FOL)/leucovorin, 5-fluorouracil and oxaliplatin (OX) (mFOLFOX6) or FOL/leucovorin, 5-fluorouracil and irinotecan (IRI) (FOLFIRI), and bevacizumab in participants with advanced solid tumors in a broad range of solid tumors. Participants with disease types selected for evaluation in this study are expected to derive clinical benefit with addition of an anti-PD-1. The study will be conducted in two parts with Part 1 consisting of dose escalation to determine the recommended phase 2 dose (RP2D) of TSR-033 as a single agent (Part 1a) and in combination with dostarlimab (Part 1c). RP2D decisions will be based on the occurrence of dose-limiting toxicities (DLTs), pharmacokinetics (PK), as well as pharmacodynamics (PDy) data. Part 2A of the study will investigate the anti-tumor activity of TSR-033 and dostarlimab in combination in participants with advanced or metastatic microsatellite stable colorectal cancer (MSS-CRC). Part 2B of the study will investigate the safety and anti-tumor activity of TSR-033 and dostarlimab in combination with chemotherapy (Cohort B1: mFOLFOX6 and Cohort B2: FOLFIRI) and bevacizumab in participants with advanced or metastatic MSS-CRC.

Timeline

Start

2017-08-08

Primary completion

2022-06-02

Completion

2023-02-13

Publications

• Hecht JR, Michot JM, Bajor D, Patnaik A, Chung KY, Wang J, Falchook G, Cleary JM, Kim R, Krishnamurthy A, Marathe O, Youssoufian H, Ellis C, Waszak A, Ghosh S, Zhang H, Yablonski K, Shah SD, Diaz-Padilla I, Ulahannan S. 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. BJC Rep. 2025 Feb 27;3(1):10. doi: 10.1038/s44276-024-00118-x.

Drugs

Indications