Efficacy Comparison of Dostarlimab Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy in Participants With Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC)

Summary

NSCLC comprises of approximately 84 percent (%) of all lung cancers and is often diagnosed at advanced stage due to poor prognosis. Dostarlimab is an immunoglobulin G (IgG)4 kappa humanized monoclonal antibody (mAb) that binds with high affinity to programmed cell death protein 1 (PD 1), resulting in inhibition of binding to programmed death ligand 1 (PD L1) and programmed death ligand 2 (PD L2). This study aims to compare the efficacy and safety PD-1 inhibitors dostarlimab and pembrolizumab, when administered in combination with chemotherapy (pemetrexed, cisplatin and carboplatin), in participants with non-squamous NSCLC without a known sensitizing epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or receptor tyrosine kinase-1 (ROS-1) mutation, BRAF V600E mutation, or other genomic aberration for which an approved targeted therapy is available. A total of approximately 240 participants will be enrolled in the study for a period of 5 years.

Timeline

Start

2020-11-19

Primary completion

2022-08-04

Completion

2024-09-10

Publications

• Background Austin D, Melhem M, Gandhi Y, Lu S, Visser S. Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. CPT Pharmacometrics Syst Pharmacol. 2023 Jan;12(1):87-94. doi: 10.1002/psp4.12878. Epub 2022 Nov 16.
• Background Lim SM, Peters S, Ortega Granados AL, Pinto GDJ, Fuentes CS, Lo Russo G, Schenker M, Ahn JS, Reck M, Szijgyarto Z, Huseinovic N, Zografos E, Buss E, Stjepanovic N, O'Donnell S, de Marinis F. Dostarlimab or pembrolizumab plus chemotherapy in previously untreated metastatic non-squamous non-small cell lung cancer: the randomized PERLA phase II trial. Nat Commun. 2023 Nov 11;14(1):7301. doi: 10.1038/s41467-023-42900-4.
• Lim SM, Ortega Granados AL, Pinto GDJ, Fuentes CS, Lo Russo G, Schenker M, Ahn JS, de Marinis F, Locke K Jr, Szijgyarto Z, Buss E, Stjepanovic N, Diaz-Padilla I, Peters S. Long-term Survival Analysis From PERLA, A Phase II Randomized Trial of Dostarlimab With Chemotherapy Versus Pembrolizumab With Chemotherapy in Metastatic Nonsquamous NSCLC. JTO Clin Res Rep. 2025 Sep 4;6(10):100900. doi: 10.1016/j.jtocrr.2025.100900. eCollection 2025 Oct.

Drugs

Indications