Daiichi Sankyo Terminates Phase 1 Development of GPR20-Targeted ADC DS-6157 in Gastrointestinal Stromal Tumor (GIST) Due to Lack of Efficacy

October 30, 2021 /Bio ValleyBIOON/ -- Japanese pharmaceutical company Daiichi Sankyo recently disclosed in its third-quarter financial report that, due to a lack of efficacy signals, the company has decidedTermination of Clinical Development of GPR20-Targeted Antibody-Drug Conjugate (ADC) DS-6157。

Daiichi-Sankyo advanced DS-6157 to Phase I clinical trials one year ago.Clinical Trial, evaluating its role asTreatmentAdvanced Gastrointestinal Stromal Tumor (GIST)A potential approach for patients. In the Q3 earnings report, the company stated that Phase 1 data showed that, in the Phase 1 dose-escalation portion,DS-6157 did not demonstrate a significant response in the treatment of GIST at any dose level.. Based on these results, the company has decided to terminate the clinical development program for DS-6157 and will not proceed with the dose escalation phase.

GPR20 is a rare G protein-coupled receptor (GPCR) highly expressed in GIST.。Interstitial cells of Cajal (ICC) are a population of non-neural interstitial cells located in the muscular layer of the gastrointestinal tract that are closely associated with nerves. They represent the cell of origin for gastrointestinal stromal tumors (GIST) and are the only GPR20-positive cells. Currently, the function of GPR20 in GIST remains unknown.

DS-6157 is a potential first-in-class GPR20-targeting ADC that conjugates a GPR20-targeting monoclonal antibody to a novel topoisomerase I inhibitor exatecan derivative (DX-8951 derivative, DXd) via a linker,Capable of targeted delivery of cytotoxic agents to cells expressing GPR20 (in GIST, interstitial cells of Cajal), compared with conventional chemotherapy, reduces systemic exposure to cytotoxic agents. Preclinical data show that DS-6157 can specifically bind to patientsTumorGPR20 on the cell surface.

DS-6157 is a Daiichi Sankyo drug.TumorIt is the fifth DXd ADC in the pipeline to enter clinical development and the second drug class co-developed with the Sarah Cannon Research Institute. In a Phase 1 clinical study initiated in May 2020, the company evaluated DS-6157 in patients with gastrointestinal stromal tumor (GIST) who experienced disease progression during or were intolerant to standard therapy.The typical treatment for GIST includes surgical resection and targeted therapy with tyrosine kinase inhibitors (TKIs).

In its third-quarter financial report, Daiichi Sankyo only stated that no significant response was observed in GIST patients treated with DS-6157, but did not share the results of the Phase 1 clinical trial. The company noted that it is continuing to analyze the study data to explore potential mechanisms behind the "non-response." The company plans to present at a scientific conference sometime in 2022.MeetingData from this Phase 1 study are presented above.

DXd-ADC Assets (Click image to view full size)

GIST is a rare, genomically driven gastrointestinal sarcoma. More than half of GISTs originate in the stomach. Most other GISTs arise in the small intestine, but GISTs can originate in any part of the gastrointestinal tract.

Although the development of DS-6157 has been discontinued, Daiichi Sankyo maintains a robust ADC drug pipeline. Earlier this year, the company and...AstraZenecaThe co-developed HER2-targeted ADC drug Enhertu was by the United StatesFDAApproved for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. Notably, Enhertu is the first HER2-targeted therapy approved for this indication in the past 10 years. Previously, Enhertu was also approved: for the treatment of HER2-positive metastatic... who have received two or more prior anti-HER2 therapies in the metastatic setting.Breast cancerAdult patients.

Daiichi Sankyo's DXd ADC product portfolio comprises 7 antibody drug assets, including Enhertu.Other ADC candidates include: (1) datopotamab deruxtecan, a TROP2-targeting ADC that is also being co-developed with AstraZeneca; (2) patritumab deruxtecan, a HER3-targeting ADC; (3) DS-7300, a B7-H3-targeting ADC; (4) DS-6157, a GPR20-targeting ADC. (Bioon.com)

Original Source:"No Clear Response" Ends Early-Stage Daiichi Sankyo ADC Program