Preliminary Data From a Phase 1/2 Trial of PDS01ADC Plus Docetaxel in mCRPC

Preliminary results from an ongoing phase 1/2 trial combining docetaxel with the tumor-targeting IL-12 immunocytokine PDS01ADC  (aka M9241) indicate promising early activity in patients with metastatic castration-resistant prostate cancer (mCRPC).

The single-arm study, presented at the American Association for Cancer Research special conference on prostate cancer research, enrolled 16 patients with progressive mCRPC, most of whom had tumors that progressed after second-line therapy including androgen deprivation and an androgen receptor pathway inhibitor. PDS01ADC is designed to recognize DNA-histone epitopes exposed in necrotic regions of tumors, leveraging the necrosis induced by docetaxel (a standard chemotherapeutic) to enhance targeted delivery and immune activation.

Among the 16 patients, with a median age of 68 years (range 45-82) and median baseline PSA of 150 ng/dL (range 14.2-2251), the median progression-free survival reached 9.6 months (range 4.3-32.2). Notably, 13 patients experienced PSA declines, with a median reduction of 40% from baseline, and 6 achieved greater than 50% declines, signals of efficacy in this heavily pretreated, third-line population.

Treatment was well-tolerated, with adverse events aligning with known docetaxel effects plus transient fever or flu-like symptoms after PDS01ADC dosing; no new safety signals emerged beyond phase 1 findings. The trial, which aims to enroll up to 24 patients total, continues with completion anticipated by late 2026, potentially offering insights into IL-12-based combinations as a strategy to boost chemotherapy responses in advanced prostate cancer.

Source.

Clinical trial.