Compendium of the most significant studies with reference to properties, intake, effects.

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.

Abstract. Neoadjuvant chemotherapy and radiation followed by surgical resection of the rectum is a standard treatment for locally advanced rectal cancer. A subset of rectal cancer is caused by a deficiency in mismatch repair. Because mismatch repair-deficient colorectal cancer is responsive to programmed death 1 (PD-1) blockade in the context of metastatic disease, it was hypothesized that checkpoint blockade could be effective in patients with mismatch repair-deficient, locally advanced rectal cancer.

Laken, H., Kehry, M., McNeeley, P., Neben, T., Zhang, J., Jenkins, D., & Wilcoxen, K. (2016). Identification and characterization of TSR-042, a novel anti-human PD-1 therapeutic antibody. European Journal of Cancer, 1(69), S102.

Yap TA, Bessudo A, Hamilton E, Sachdev J, Patel MR, Rodon J, Evilevitch L, Duncan M, Guo W, Kumar S, Lu S, Dezube BJ, Gabrail N. IOLite: phase 1b trial of doublet/triplet combinations of dostarlimab with niraparib, carboplatin-paclitaxel, with or without bevacizumab in patients with advanced cancer. J Immunother Cancer. 2022 Mar;10(3):e003924. doi: 10.1136/jitc-2021-003924. 

Abstract. The objective of this trial was to determine the recommended phase 2 doses (RP2Ds) and to assess the safety and efficacy of the programmed cell death protein 1 (PD-1) inhibitor dostarlimab in combination with (1) the poly(ADP-ribose) polymerase inhibitor niraparib with or without vascular endothelial growth factor inhibitor bevacizumab or (2) carboplatin-paclitaxel chemotherapy with or without bevacizumab, in patients with advanced cancer.

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-PD-1 monoclonal antibody dostarlimab for patients with recurrent or advanced dMMR endometrial cancer. Future Oncol. 2021 Oct 1;17(29):3781-3785. doi: 10.2217/fon-2021-0598. 

Abstract. This document provides a short summary of the GARNET trial which was published in JAMA Oncology in October 2020. At the end of this document, there are links to websites where you can find more information about this study. The trial enrolled adult participants with advanced solid tumors.

Lu S, Bowsher RR, Clancy A, Rosen A, Zhang M, Yang Y, Koeck K, Gao M, Potocka E, Guo W, Jen KY, Im E, Milton A. An Integrated Analysis of Dostarlimab Immunogenicity. AAPS J. 2021 Jul 29;23(5):96. doi: 10.1208/s12248-021-00624-7.

Abstract.  Here, we report the results of an immunogenicity analysis of dostarlimab monotherapy in patients enrolled in the GARNET trial, a multicenter, open-label, single-arm phase 1 study.

Rubio-Pérez J, Hernández R, Hernández T, Doger B, Casado V, Moreno V. Dostarlimab for the treatment of endometrium cancer and other solid tumors. Drugs Today (Barc). 2021 Mar;57(3):187-197. doi: 10.1358/dot.2021.57.3.3233363.

Abstract. Here we summarize the development of this compound as well as the current preclinical and clinical data and potential future development.

Bowers PM, Horlick RA, Neben TY, Toobian RM, Tomlinson GL, Dalton JL, Jones HA, Chen A, Altobell L 3rd, Zhang X, Macomber JL, Krapf IP, Wu BF, McConnell A, Chau B, Holland T, Berkebile AD, Neben SS, Boyle WJ, King DJ. Coupling mammalian cell surface display with somatic hypermutation for the discovery and maturation of human antibodies. Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20455-60. doi: 10.1073/pnas.1114010108.

Abstract. A novel approach has been developed for the isolation and maturation of human antibodies that replicates key features of the adaptive immune system by coupling in vitro somatic hypermutation (SHM) with mammalian cell display.