On October 22, 2020 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that the first patient has been dosed in a first-in-human global phase 1 study evaluating DS-1055, a GARP directed immuno-oncology therapy, in patients with advanced or metastatic solid tumors who have progressed on standard treatments including checkpoint inhibitors (Press release, Daiichi Sankyo, OCT 22, 2020, https://www.businesswire.com/news/home/20201021006132/en/Daiichi-Sankyo-Initiates-Phase-1-Trial-with-Immuno-Oncology-Therapy-DS-1055-Targeting-GARP-on-Activated-Regulatory-T-Cells [SID1234568861]).

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Immune checkpoint inhibitors have significantly impacted the treatment paradigm for several cancers over the past decade with improved survival for subsets of patients, but the majority of patients do not respond to current therapies or eventually develop resistance.1 GARP is highly expressed on activated regulatory T cells (Tregs) and contributes to their immunosuppressive activity.2 Research suggests that targeting GARP on Tregs may be a promising new immune intervention strategy.2 There are no GARP directed therapies currently approved for cancer treatment.

"We are pleased to initiate clinical development to further evaluate the novel mechanism behind DS-1055, which was specifically designed to decrease the number of GARP expressing regulatory T cells and restore antitumor immune response," said Arnaud Lesegretain, Vice President, Global Oncology Development, Alpha Portfolio, Daiichi Sankyo. "Evidence suggests that DS-1055 could serve as a new type of immune-based therapy for patients with various cancers, including those resistant or refractory to checkpoint inhibitors."

About the Study

The first-in-human, global, multi-center, open-label phase 1 dose escalation study will evaluate the safety, tolerability and preliminary efficacy of DS-1055 in adult patients with relapsed/refractory advanced or metastatic head and neck, gastric and esophageal cancers and other tumor types. The purpose of this study is to determine the maximum tolerated dose and recommended dose of DS-1055 for further study.

The study will evaluate safety endpoints including dose-limiting toxicities and adverse events. Efficacy endpoints include objective response rate, disease control rate, duration of response, time to response, progression-free survival and overall survival. Pharmacokinetic, immunogenicity and biomarker endpoints will also be assessed.

Approximately 40 patients will be enrolled in the U.S. and Japan. For more information visit ClinicalTrials.gov (NCT04419532).

About DS-1055

DS-1055 is a monoclonal antibody designed to target GARP (Glycoprotein-A Repetitions Predominant), a transmembrane protein expressed on the surface of activated Tregs in the tumor microenvironment. DS-1055 was designed to promote antitumor immunity through the depletion of GARP positive Tregs.

Tregs are involved in immune tolerance and have strong immunosuppressive activity.3 Tregs are accumulated in the tumor microenvironment, where they are activated and inhibit antitumor immunity through various mechanisms leading to suppression of effector T cells with antitumor activity.3 Tregs also cause resistance to immune checkpoint inhibitors.1 High Treg presence in the tumor microenvironment is associated with poor prognosis in various types of cancer.4

Targeting GARP, which is selectively expressed on activated Tregs and contributes to the function of Tregs, may be a way to decrease the number of functional Tregs in the tumor microenvironment and restore antitumor immunity.2 Preclinical evidence has shown that depletion of Tregs results in antitumor activity.5

DS-1055 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.