Where did this thing come from?
Daiichi Sankyo shared phase 1 data from its investigational HER2-targeted ADC DS-8201a at ESMO this weekend: no DLTs, and among the 20 patients evaluable for response, there was an ORR of 35% and a DCR of 90%.
DS seemed to be taking all comers for this dose escalation cohort: 22 breast and gastric subjects, high HER2-expressing and low. I winced at the patient selection criteria, but that 35% ORR is worth a look. Apparently the 15 subjects with with traditionally-defined HER2+ disease (HER2 expression of IHC3+ or IHC2+/FISH+) had a DCR of 100%.
Median PFS has not been reached, and 17 subjects are still on treatment.
There is one HER2+ targeted ADC on the market now, T-DM1 (Kadcyla). T-DM1 has been a disappointment for Roche: there was a drawn-out road to market, during which time the FDA was mobbed by pitchfork-wielding villagers who accused the agency of murdering HER2+ patients who needed the drug to live. Once T-DM1 was finally approved, it turned out to perform just okay in the metastatic setting and was hugely overshadowed by Perjeta (the UK Cancer Drugs Fund actually tried to cut T-DM1 from the list in 2015, a decision that was ultimately reversed). So it should be noted that outperforming T-DM1 is not such a game-changer, but DS does report that, for DS-8201a, “In 12 evaluable HER2+ breast cancer patients previously treated with [T-DM1], the objective response rate was 42% with a disease control rate of 92%.”
So what is DS-8201a? The press release describes it as a “humanized anti-HER2 antibody attached by a peptide linker to a novel topoisomerase I inhibitor (DXd) payload, utilizing Daiichi Sankyo’s proprietary payload and linker-payload technology.”
Well, that’s specific.
It sounds a little like the Immunomedics ADC IMMU-132, which targets surface antigen Trop-2 and has an irinotecan (also a top I inhibitor) payload. The drug is in development for TNBC and SCLC/NSCLC, and we haven’t seen any new data on it in a while (though Immunomedics doesn’t mind passing off old data as new data, ahem.)
Without much happening in HER2+ drug development, this DS agent may be one to watch. Trial information is here: NCT02564900.