On October 29, 2021 Daiichi Sankyo’s investigational GPR20 directed antibody drug conjugate DS-6157 reported that entered the clinic as a potential treatment for patients with advanced gastrointestinal stromal tumor (GIST), the company has terminated the clinical program due to a lack of clinical response (Press release, Daiichi Sankyo, OCT 29, 2021, https://www.biospace.com/article/daiichi-sankyo-scraps-phase-i-adc-aimed-at-gist-following-poor-clinical-findings/ [SID1234593974]).

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Daiichi Sankyo announced the decision in its third quarter financial report this morning. The company said that the Phase I data yielded "no clear responses in GIST patients at any dose level in Phase I dose escalation. Based on those results, the company opted to terminate the development of DS-6157 without proceeding to dose escalation.

DS-6157 is a potential first-in-class GPR20 targeting ADC. By using ADCs, companies aim to produce the payload of cytotoxic chemotherapy to cancer cells by using linker technology attached to a monoclonal antibody. When delivered, the drug binds to a specific target on the cancer cell. In the case of DS-6157, that target was cancer cells that express G Protein-Coupled Receptor (GPR20), which are typically found in gastrointestinal stromal tumors. Preclinical data showed that DS-6157 specifically binds to GPR20 on the surface of individual tumor cells.

DS-6157 was the fifth DXd ADC from the oncology pipeline of Daiichi Sankyo to enter clinical development, and it is the second drug type developed with Sarah Cannon Research Institute. In the Phase I study initiated in May 2020, the company was assessing the drug in GIST patients who have progressed on, or are intolerant to, standard treatment. Typical treatment for this type of cancer includes recommended surgery and targeted therapy with tyrosine kinase inhibitors.

Other than its notice that there were no clear responses in GIST patients, Daiichi Sankyo has not shared clinical results from the Phase I study. The company did note that it is continuing to examine the study’s information to explore "possible mechanisms of the non-responsiveness." The company plans to present the Phase I data at a scientific conference sometime in 2022.

GIST is a rare, genomically driven sarcoma of the gastrointestinal tract. More than half of GISTs start in the stomach. Most of the others form in the small intestine, but GISTs can begin anywhere along the gastrointestinal tract.

While DS-6157 development has been scrapped for this indication, Daiichi Sankyo maintains a strong pipeline of ADC drugs. Earlier this year, Enhertu, an ADC co-developed with AstraZeneca, was approved to treat gastric cancer by the U.S. Food and Drug Administration. It was the first HER2-directed drug to be approved for this indication in the past 10 years.

Enhertu was previously approved as a treatment for adults with unresectable or metastatic HER2-positive breast cancer who have had two or more previous anti-HER2-based therapies in the metastatic setting.

Daiichi Sankyo’s DXd ADC portfolio comprises seven antibody drug assets, including Enhertu. Other ADC candidates include datopotamab deruxtecan, a TROP2 directed ADC, which is also being jointly developed with AstraZeneca; patritumab deruxtecan, a HER3 directed ADC; DS-7300, a B7-H3 directed ADC; and DS-6157, a GPR20 directed ADC. The last three assets are being developed in collaboration with Sarah Cannon Cancer Institute.