Dostarlimab is a large protein molecule, a revolutionary anti-PD-1 (programmed cell death 1) immunoglobulin G4 monoclonal antibody, humanised, derived from a mouse mAb using the AnaptysBio SHM-XEL system.

Results from clinical studies have demonstrated long-lasting and significant antitumour activity with a good level of safety (1).  It is currently undergoing advanced evaluation in the GARNET study (2).

A further prospective phase 2 study published in June 2022 confirmed the efficacy of Dostarlimab on rectal cancer although the conclusions cautiously recommended longer follow-up to assess the duration of response (3).

The antitumour activity of Dostarlimab is also confirmed in several tumour types such as endometrial cancer and lung carcinoma, which has earned its approval in the United States as an effective monotherapy in cases of solid tumours that have progressed or have not had satisfactory treatment alternatives.

Dostarlimab studies

Dostarlimab (JEMPERLI) product monograph:

Jemperli Product Monograph (gsk.com)

Protein Chemical Formula  C₆₄₂₀H₉₈₃₂N₁₆₈₀O₂₀₁₄S₄₄

Protein Average Weight  144000.0 Da

CAS   2022215-59-2

UNII   P0GVQ9A4S5

Synonyms

• TSR 042
• Immunoglobulin G4, anti-programmed cell death protein 1 (PDCD1) (humanized clone ABT1 gamma4-chain), disulfide with humanized clone ABT1 kappa-chain, dimer
• JEMPERLI
• WBP-285
• P0GVQ9A4S5

References____________________________________________________________________

(1) Oaknin A, Tinker AV, Gilbert L, Samouëlian V, Mathews C, Brown J, Barretina-Ginesta MP, Moreno V, Gravina A, Abdeddaim C, Banerjee S, Guo W, Danaee H, Im E, Sabatier R. Clinical Activity and Safety of the Anti-Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients With Recurrent or Advanced Mismatch Repair-Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial. JAMA Oncol. 2020 Nov 1;6(11):1766-1772. doi: 10.1001/jamaoncol.2020.4515.

(2) Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors - Full Text View - ClinicalTrials.gov 

(3) Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, El Dika IH, Segal N, Shcherba M, Sugarman R, Stadler Z, Yaeger R, Smith JJ, Rousseau B, Argiles G, Patel M, Desai A, Saltz LB, Widmar M, Iyer K, Zhang J, Gianino N, Crane C, Romesser PB, Pappou EP, Paty P, Garcia-Aguilar J, Gonen M, Gollub M, Weiser MR, Schalper KA, Diaz LA Jr. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022 Jun 5. doi: 10.1056/NEJMoa2201445.