Daiichi Sankyo scraps early-stage ADC program in gastrointestinal tumors after first phase fail

29 Oct 2021
endpts.com
AntibodyADCCollaborate
Driven by a series of wins for its antibody-drug conjugate pipeline, Daiichi Sankyo has earned a reputation as an ADC expert with a successful partnership with AstraZeneca under its belt. But failures do happen — and for Daiichi, it’s where the company least expected it. Daiichi has scrapped development of DS-6157, an ADC targeting the GPR20 protein in gastrointestinal stromal tumors (GIST), after the drug failed a Phase I test, the drugmaker revealed in its Q2 update Friday. During the dose escalation phase of the study, Daiichi said DS-6157 failed to spur any responses in patients, giving the drugmaker little reason to move ahead into dose expansion. Daiichi said it would look for possible explanations behind why the drug wasn’t effective and is planning to present full results at a 2022 medical meeting. It’s a rare setback for Daiichi’s ADC program, which has churned out two highly watched drugs currently part of a multibillion-dollar collaboration with AstraZeneca. DS-6157 targeted GPR20, a G protein-coupled receptor (GPCR)GPCR) highly expressed in GIST but without a known function in causing disease, Daiichi said. Scrapping DS-6157 won’t do much to stop Daiichi’s momentum here, though, given the spate of recent successes from its pipeline, including some eye-popping data from HER2-targeting ADC Enhertu. At this year’s ESMO, Daiichi and AstraZeneca rolled out Phase III data showing Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared to Roche’s ADC Kadcyla. The results came in second-line unresectable and/or metastatic HER2-positive breast cancerHER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo. Median progression-free survival for Enhertu as determined by a blinded independent review committee had not been reached at 15.5- and 13.9-month check-ins, the partners said, compared with a median PFS of 6.8 months for Kadcyla, otherwise known as T-DM1. But on a secondary endpoint determining PFS by investigator review, Enhertu posted a jaw-dropping three-fold increase over Kadcyla at 25.1 months versus 7.2 months, respectively. Enhertu was approved as a third-line or later treatment for HER2-positive metastatic breast cancerHER2-positive metastatic breast cancer back in late 2019, putting wind in the sails of the Daiichi pact for the drug and a follow-up ADC dubbed Dato-DXd targeting the TROP2 protein. Enhertu is one of a group of “third-gen” ADCs that are showing promise in early-line cancers given their targeted efficacy and less onerous safety profiles than their older counterparts.
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