DS-7300 Data at ESMO Shows Promising Early Clinical Activity in Patients with Advanced Solid Cancers

TOKYO & MUNICH & BASKING RIDGE, N.J.

New first-in-human data from DS-7300, a B7-H3 directed DXd antibody drug conjugate (ADC) being developed in strategic collaboration between Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and Sarah Cannon Research Institute, showed promising early clinical activity in patients with several types of advanced solid tumors. These results from the dose escalation portion of a phase 1/2 study of DS-7300 were presented during a Proffered Paper session (#513O) at the European Society for Medical Oncology (#ESMO21) 2021 Virtual Congress.

B7-H3 is frequently overexpressed in a wide range of cancers including lung, prostate, breast, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma, and its overexpression is associated with poor prognosis.^1,2,3 No B7-H3 directed therapies are currently approved for treatment of any cancer.

DS-7300 was tolerated across all dose levels (0.8 mg/kg -16.0 mg/kg) with no dose-limiting toxicities observed in 70 patients enrolled. The most common treatment emergent adverse events (TEAEs) overall in ≥10% of patients were nausea (55.7%), infusion-related reaction (40.0%), decreased appetite (28.6%), vomiting (27.1%), fatigue (21.0%), chills (12.9%), pyrexia (12.9%), dehydration (11.4%) and diarrhea (11.4%). Grade 3 or higher TEAEs regardless of causality occurred in 31.4% of patients (n=22) with the most common being anemia (15.7%) and lymphocyte count decreased (2.8%). One patient receiving the 16.0 mg/kg dose developed interstitial lung disease (ILD) that was associated with death (grade 5) that was adjudicated as treatment related. One case of grade 1 ILD at the 12.0 mg/kg dose that was pending adjudication as of data cut-off of July 21, 2021 has since been adjudicated as treatment related.

Preliminary efficacy results include 15 partial responses (PR), 10 confirmed PRs with 5 additional PRs awaiting confirmation, in patients with a range of solid tumors including metastatic castration-resistant prostate cancer, head and neck squamous cell carcinoma, small cell lung cancer, endometrial cancer, esophageal squamous cell carcinoma and squamous non-small cell lung cancer at doses from 4.8 mg/kg to 16.0 mg/kg. Stable disease has been reported in an additional 32 patients including 24 patients who are still being treated with various doses of DS-7300 as of data cut-off of July 21, 2021. Patients enrolled in the dose escalation study received a median of four prior lines of therapy (range, 1-10).

“These initial safety and efficacy results of DS-7300 are encouraging as we observed that most patients in the study experienced some level of tumor shrinkage,” said Melissa Johnson, MD, Director of the Lung Cancer Research Program at Sarah Cannon Research Institute. “Based on these results, we are moving forward with the dose expansion part of the study where we are enrolling patients with metastatic small cell lung cancer, esophageal squamous cell cancer and castration-resistant prostate cancer to further evaluate the potential role of DS-7300 in these cancers.”

“These first-in-human results provide preliminary evidence that targeting B7-H3 with DS-7300 may be an effective treatment strategy across several types of cancer where current treatment options are limited,” said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. “Additionally, these results seen with DS-7300, our fourth DXd ADC in clinical development, may further validate the portability of our DXd ADC technology to other targets to create potential new treatments for patients with cancer.”

About B7-H3

B7 homologue 3 (B7-H3) is a transmembrane protein belonging to the B7 family. B7-H3 plays a role in tumor growth as well as in immune response.^4,5 B7-H3 is frequently overexpressed in various cancers including lung, prostate, breast, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma and its overexpression is associated with poor prognosis.^1,2,3

About the DS-7300 Study

This first-in-human, open-label phase 1/2 study is evaluating 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) is assessing the safety and tolerability of increasing doses of DS-7300 given every three weeks to determine the maximum tolerated dose (MTD) or recommended dose for expansion (RDE). This portion of the trial enrolled 70 patients with advanced/unresectable or metastatic castration-resistant prostate cancer, head and neck squamous cell carcinoma, small cell lung cancer, endometrial cancer, esophageal squamous cell carcinoma, squamous non-small cell lung cancer, breast cancer, melanoma and bladder cancer.

The second part of the study (dose expansion) will be evaluating the safety, tolerability and preliminary activity of DS-7300 at various doses. This portion of the study currently consists of three cohorts of patients with selected advanced/metastatic solid tumors including small cell lung cancer, esophageal squamous cell cancer, and castration-resistant prostate cancer. Additional or alternative indications may be added to expansion cohorts based on preliminary signals of activity.

The study is evaluating 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 also will be assessed.

Patient enrollment into the dose expansion part of the study is underway in Asia and North America. For more information, please visit ClinicalTrials.gov.

About DS-7300

DS-7300 is an investigational B7-H3 directed ADC and is one of six ADCs currently in clinical development in the oncology pipeline of Daiichi Sankyo. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, DS-7300 is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable linker. DS-7300 is being developed through a strategic collaboration with Sarah Cannon Research Institute, with study operational oversight and delivery provided through Sarah Cannon’s early phase Oncology CRO, Sarah Cannon Development Innovations.

DS-7300 is an investigational medicine that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo in Oncology

The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd antibody drug conjugate (ADC) technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon, our small molecule structure-guided R&D center in the U.S. We also work alongside leading academic and business collaborators to further advance the understanding of cancer as Daiichi Sankyo builds towards our ambitious goal of becoming a global leader in oncology by 2025.

About Daiichi Sankyo

Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.” For more information, please visit www.daiichisankyo.com.

References:

¹ Dong P, et al. Front Oncol. 2018;8:264.

² Picarda E, et al. Clin Cancer Res.2016;22(14):3425-3431.

³ Bendell JC, et al. J Clin Oncol. 2020;39(15 suppl 1). Abstract 2020.

⁴ Zhang et al. Oncotarget. 2017 Nov 3; 8(54): 93156–93167.

⁵ Castellanos J et al. Am J Clin Exp Immunol 2017;6(4):66-75.

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