The phase 3 results of the study, known as ASCENT, were published in the New England Journal of Medicine. SG, which was developed and is manufactured by Immunomedics, a subsidiary of Gilead Sciences, received accelerated approval by the U.S. Food and Drug Administration in April 2020 on the basis of favorable phase 1/2 clinical trials, with full approval contingent on the confirmatory phase 3 results.
ASCENT is a global study to evaluate the safety and efficacy of the antibody drug conjugate compared to chemotherapy in 529 patients with metastatic triple-negative breast cancer whose cancer had relapsed or was resistant to at least two other forms of therapy.
The investigators found that median progression-free survival with the ADC agent was 5.6 months compared to 1.7 months with chemotherapy, and that median overall survival was 12.1 months with the ADC agent compared to 6.7 months with chemotherapy. The study also found that the response rate – that is, shrinkage in the size of the metastatic tumor sites – was 35% after administration of ADC compared to 5% with chemotherapy.
No clear response ends early-stage Daiichi Sankyo ADC program
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. While the function of GPR20 in GIST is unknown, Daiichi hypothesized that over-expression 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 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.
Seagenbets its newly acquired HER2-ADC disitamabvedotin can challenge Enhertu
Talking about the competitor product, Enhertu, Seagen CEO Clay Siegall said the molecule internalizes, but it’s kind of a middle of the road internalization. The antibody used in RC48, which is what we licensed from RemeGen, was selected based on incredibly rapid internalization.But both Enhertu and Kadcyla are cut from the same cloth, as they use Herceptin as their antibody. Meanwhile, the antibody component for Seagen’s new drug, disitamab, is a novel medicine. Compared to Enhertu and Kadcyla, disitamabvedotin has superior tumor-binding ability and tumor uptake, Seagen says. That’s what was attractive to Seagen, which has established itself as perhaps the premier developer of ADCs thanks largely to its payload-linker technology.