Dual-target ADC shows promising PFS signal in mCRPC | ASCO 2026

For patients with metastatic castration-resistant prostate cancer (mCRPC), the treatment landscape has grown increasingly complex. Despite meaningful advances in recent years, including novel hormone agents, taxane chemotherapy, and PSMA-targeted radioligand therapy, many patients continue to progress and face limited options with each subsequent line of treatment.

At the 2026 American Society of Clinical Oncology (ASCO) annual meeting, results from a first-in-human phase 1 dose escalation study of ABBV-969 demonstrated significant potential in mCRPC. ABBV-969 is a first-in-class antibody drug conjugate that takes a dual-targeting approach, going after both PSMA and STEAP1, two antigens overexpressed in more than 80% of metastatic prostate cancer tumors. The payload is a topoisomerase 1 inhibitor, a mechanism now demonstrating broad utility across ADC development in oncology.

What set these early data apart was not just the mechanism but the depth and durability of response observed in a patient population that had already been heavily pretreated. With a median of five prior lines of therapy and nearly half of patients having previously received lutetium-177 PSMA-617, the activity signal is exciting, lead author Tanya Dorff, M.D., FASCO, division chief of the Genitourinary Disease Program at City of Hope, told Managed Healthcare Executive^®.

Among patients with RECIST-evaluable disease, the confirmed objective response rate came in at 45%, including a 17% complete response rate. Radiographic progression-free survival data, also presented, added further weight to the findings.

“Here, we're seeing radiographic progression-free survival over 15 months,” Dorff said. “That is really striking to me. And then the RECIST objective responses — to have 29 of our 41 patients evaluable, and in that setting, 45% having a confirmed objective RECIST response — that just speaks volumes to the efficacy, including 17% complete response, which is challenging when you have bone metastases. I think we'll need to drill down into that for patients with mixed soft tissue and bone [metastases], but to me, the efficacy results are really exciting.”