Daiichi jettisons ADC after flunking early solid tumor test

Daiichi Sankyo’s antibody-drug conjugate (ADC) team has hit a rare bump in the road, dumping a gastrointestinal stromal tumor (GIST) candidate after seeing “no clear responses” in a phase 1 trial.

Daiichi took DS-6157 into the clinic in light of the unmet need in GIST and evidence that GPR20 is selectively and abundantly expressed in the indication. Tyrosine kinase inhibitors such as Gleevec are already used to treat GIST, but many patients progress after developing resistance mutations. Equally, the therapies have limited efficacy in some subsets of GIST patients. 

While the function of GPR20 in GIST is unknown, Daiichi hypothesized that overexpression of the G protein-coupled receptor makes it an attractive target for an ADC, offering it a way to get a payload to cancer cells without harming healthy tissues and thereby address the need for a new mechanism of action in GIST. That hypothesis fell at the first clinical hurdle.

Daiichi is yet to share data from the study but used its second-quarter results (PDF) to reveal it saw “no clear responses” at any of the six dose levels tested in the phase 1 trial. The lack of activity led Daiichi to scrap DS-6157 development without moving into the dose-expansion portion of the study. 

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Work is now underway to figure out what went wrong in the study and, as Daiichi put it, to “explore possible mechanisms of the non-responsiveness.” Daiichi plans to share phase 1 data at a scientific conference in its next financial year.

The failure of DS-6157 still leaves Daiichi with a broad ADC pipeline. Having already brought the AstraZeneca-partnered HER2 ADC Enhertu to market, Daiichi is advancing a handful of candidates against targets including TROP2 and HER3 through the clinic. Daiichi moved CDH6-directed DS-6000, the sixth oncology ADC from its platform, into the clinic earlier this year.