Phase 1 Trial: ROR1-Targeting ADC HDM2005 Shows Early Antitumor Activity in Heavily Pretreated Prostate Cancer

Early results presented at ESMO 2026 suggest that HDM2005, an experimental antibody-drug conjugate (ADC) targeting ROR1, may have antitumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC) who have exhausted several established treatment options.

HDM2005 is designed to recognize ROR1, a protein expressed by certain cancer cells, and deliver the chemotherapy agent monomethyl auristatin E (MMAE) directly to the tumor. This approach aims to concentrate the cytotoxic drug in cancer tissue, although toxicity to healthy cells remains possible.

The multicenter, open-label phase I study enrolled patients whose disease had progressed following at least one androgen receptor pathway inhibitor and one taxane-based chemotherapy regimen.

As of March 25, 2026, 17 patients had received treatment, and nearly 95% had undergone at least three previous lines of therapy.

Among the 10 patients evaluable for tumor response, three achieved a partial response (30%) and five had stable disease, resulting in a disease control rate of 80%. Three patients with stable disease also experienced reductions in the size of their target tumors.

PSA responses were observed as well. Among 16 evaluable patients, nine (56.3%) experienced a PSA reduction of at least 30%, while four (25%) achieved a reduction of at least 50%.

However, toxicity was substantial. All 17 patients experienced treatment-related adverse events, with grade 3 or higher events occurring in 59%. Severe neutropenia was particularly frequent, affecting 41% of patients. Treatment-related serious adverse events occurred in 41%, and 29% required dose reductions. No treatment-related discontinuations or deaths were reported.

These results provide an early indication that targeting ROR1 could represent another therapeutic strategy for advanced prostate cancer, including patients previously exposed to both hormonal therapies and chemotherapy.

Source.