Nashville, Tenn., Tokyo, Munich and Basking Ridge, NJ - (October 31, 2019) – Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and Sarah Cannon Research Institute (Sarah Cannon) announced today that the first patient has been dosed in a first-in-human phase 1/2 study evaluating DS-7300, an investigational B7-H3 targeting antibody-drug conjugate (ADC), in patients with various advanced solid tumors that have progressed on standard treatments or for whom no standard treatment exists.
The study is the first in the strategic oncology partnership announced between Daiichi Sankyo and Sarah Cannon, designed to expedite and optimize the global clinical development of Daiichi Sankyo’s novel ADCs and other targeted cancer therapies by combining the operational and scientific expertise of both organizations.
DS-7300 is the fourth ADC in clinical development utilizing Daiichi Sankyo’s proprietary DxD technology and was designed to target and deliver chemotherapy inside cancer cells that express the B7-H3 protein. B7-H3 is frequently overexpressed in various types of cancers and has been associated with disease progression and poor prognosis in many tumor types.1 No B7-H3 targeting therapies are currently approved for the treatment of any cancer.
“This first-in-human phase 1/2 trial will evaluate the potential for DS-7300 to serve as a new model of targeted therapy for patients with several types of advanced cancers where the B7-H3 protein is overexpressed,” said Antoine Yver, MD, MSc, EVP & Global Head of Oncology Research and Development, Daiichi Sankyo. “Based on our preclinical assessments, the trial will focus initially on patients with non-small cell lung, head and neck, esophageal, and other cancers. We also will continue to conduct important biomarker and translational research to further assess the role this promising therapeutic target may play in the treatment of various cancers.”
“Given the prevalence of B7-H3 in certain tumors, we hope this unique approach will help us to more effectively target a number of cancer types,” said Johanna Bendell, MD, Chief Development Officer, Sarah Cannon. “By combining Sarah Cannon’s expertise in developing novel therapies and Daiichi Sankyo’s capabilities in compound development, we have been able to expand our reach to patients across the U.S. and Japan who vitally need advanced treatment options.”
B7-H3 (B7 homologue 3) is a transmembrane protein belonging to the B7 family. B7-H3 plays a role in tumor growth as well as in immune response.1,2 B7-H3 is highly expressed on various types of tumors including lung, head and neck, esophageal, prostate, endometrial and breast cancers.1 In preclinical studies, DS-7300 demonstrated activity in B7-H3 expressing tumors, and activity was associated with target expression levels.
Based on initial preclinical research into the construct necessary for optimized safety and efficacy in B7-H3 expressing tumors, DS-7300 was engineered with a new proprietary Daiichi Sankyo technology, DAR-controlled conjugation, to create a drug-to-antibody ratio (DAR) of four. The technology has been used also to prepare DS-1062, Daiichi Sankyo’s TROP2 ADC under clinical development in patients with NSCLC who have failed standard of care, including immune checkpoint inhibitors.
About the Study
The first-in-human, open-label phase 1/2 study will investigate the safety, tolerability and preliminary activity of DS-7300 in adult patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerable to standard treatment or for whom no standard treatment exists.
The first part of the study (dose escalation) will assess the safety and tolerability of increasing doses of DS-7300 to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE). This portion of the trial will enroll approximately 40 patients with advanced/unresectable or metastatic squamous cell head and neck cancers, squamous cell esophageal cancer, squamous and adenocarcinoma cell non-small cell lung cancer (NSCLC), and other tumor types (ten total). The second part of the study (dose expansion) will evaluate the safety, tolerability and preliminary activity of DS-7300 at the RDE and assess overall survival. This portion of the trial will include three cohorts of 40 patients each, potentially including patients with advanced/unresectable or metastatic squamous cell head and neck cancers, squamous cell esophageal cancer, and squamous NSCLC. Additional or alternative indications may be added to expansion cohorts based on preliminary signals of activity.
The study will evaluate safety endpoints including adverse events and efficacy endpoints including objective-response rate, duration of response, disease control rate, time to response, progression-free survival, and overall survival. Pharmacokinetic endpoints and exploratory biomarker and immunogenicity endpoints will also be assessed.
A total of approximately 160 patients are expected to be enrolled in this study in the U.S. and Japan. For more information, please visit ClinicalTrials.gov
DS-7300 is an investigational B7-H3 targeting ADC and one of four ADCs under clinical development in Daiichi Sankyo’s Cancer Enterprise pipeline. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary DxD ADC technology, DS-7300 is comprised of a humanized anti-B7-H3 monoclonal antibody, which is attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way the chemotherapy is commonly delivered.
DS-7300 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.
1 Zhang et al. Oncotarget. 2017 Nov 3; 8(54): 93156–93167.
2 Castellanos J et al. Am J Clin Exp Immunol 2017;6(4):66-75.