AstraZeneca has shared an early look at the performance of its in-house antibody-drug conjugate (ADC) technology, publishing phase 1 data on candidates that could compete with molecules from AbbVie and Pfizer.
The Anglo-Swedish drugmaker is a leading light in the hot ADC space, but its successes to date have come from deals with Daiichi Sankyo, not its own labs. That could change in the future. AstraZeneca has used its in-house linker and topoisomerase I payload technologies to create a set of internal ADCs, including a candidate aimed at B7-H4, called AZD8205, and at folate receptor alpha (FRα), called AZD5335.
Both those prospects are in phase 1/2a clinical trials. The European Society for Medical Oncology 2024 Congress gave AstraZeneca an opportunity to discuss what it has seen so far in the early-phase studies.
AstraZeneca presented data on 47 patients who received one of four doses of AZD8205. The candidate is designed to deliver a payload to cells that express B7-H4, a receptor found in endometrial, ovarian and breast cancers as well as in cholangiocarcinoma. Pfizer acquired a rival ADC, which entered the clinic just after AZD8205, as part of its takeover of Seagen.
In the heavily pretreated study population, AstraZeneca saw nine partial responses split evenly across endometrial, ovarian and breast cancers. There were no responses in the cholangiocarcinoma cohort. The benefits were durable in some patients, with responses and stable disease continuing for up to 76 weeks as of the data cutoff.
AstraZeneca is continuing to study AZD8205 as a monotherapy in dose optimization expansion cohorts of patients with endometrial, ovarian, breast and biliary tract cancers. Investigators are also testing the ADC in combination with the PD-1xTIGIT bispecific rilvegostomig in a dose escalation study.
A poster on AZD5335 offered another opportunity to gauge the progress of AstraZeneca’s internal ADCs. That candidate hits the same target as Elahere, the ADC that AbbVie acquired in its $10 billion takeover of ImmunoGen. Elahere received full FDA approval in ovarian cancer this year, but AstraZeneca believes its candidate may have activity at lower levels of FRα expression than AbbVie’s drug.
The poster features data on 39 ovarian cancer patients who received one of five doses of AZD5335. In the 38 dosed patients with an available on-treatment scan at data cutoff, AstraZeneca reported a 34.2% response rate. The response rate was 46.2% in participants with high FRα and 35.7% in patients with low FRα. Excluding the lowest dose boosted the response rates to 55.6% and 41.7%, respectively.
The cohorts are small—there were nine people in the analysis that yielded the 41.7% response rate—but there are early signs AZD5335 may be competitive. Elahere achieved (PDF) a response rate of 31.7% in the trial that supported its approval. That trial enrolled patients who were positive for FRα expression.
AstraZeneca’s updates also include results that offer encouragement for its broader effort to develop ADCs in-house. The pharmacokinetic profiles of both candidates support dosing every three weeks. That is the same dosing schedule as approved ADCs including Elahere and AstraZeneca and Daiichi’s Enhertu, suggesting the candidates have acceptable linker-payload stability in plasma.