Docetaxel plus tumor-targeting IL-12 yields promising activity in mCRPC

Preliminary results from a phase 1/2 trial (NCT04633252) of docetaxel plus the IL-12 antibody drug conjugate, PDS01ADC, were recently presented at the American Association of Cancer Research (AACR) special conference on prostate cancer research, showing encouraging early activity in patients with metastatic castration-resistant prostate cancer (mCRPC).¹

According to the authors, PDS01ADC is “a tumor-targeting IL-12 that recognizes DNA-histone epitopes exposed on necrotic regions of tumors.” Preclinical modeling studies indicated potential synergy between PDS01ADC and docetaxel, a necrosis inducing chemotherapeutic agent.

"These findings reinforce the potential of our tumor-targeting IL-12 immunocytokine to enhance the efficacy of existing therapies across multiple solid tumor types," said Frank Bedu-Addo, PhD, president and CEO of PDS Biotech, in a news release on the findings.²

In total, the single-arm study is enrolling up to 24 adult patients with mCRPC with progressive disease. For the study, patients receive standard-of-care docetaxel at 75 mg/m² every 3 weeks in combination with subcutaneous PDS01ADC at 12 mcg/kg with each cycle of chemotherapy starting with cycle 2. The primary end point is progression-free survival (PFS).

At the time of data presentation, the trial had enrolled 16 patients with mCRPC across both the phase 1 and phase 2 portions of the study. The majority of patients had tumors that had progressed following second-line therapy with androgen deprivation therapy and an androgen receptor pathway inhibitor. The median age of participants was 68 years (range, 45 to 82), and the median baseline prostate-specific antigen (PSA) was 150 ng/dL (range, 14.2 to 2251).

Overall, the median PFS with the combination was 9.6 months (range, 4.3 to 32.2). Thirteen of sixteen patients experienced a decline in PSA levels, with a median decline from pre-treatment baseline of 40%. Additionally, 6 of 16 patients experienced a PSA decline greater than 50%.

According to the authors, treatment was also well-tolerated, with adverse events (AEs) consistent with the results from the phase 1 portion of the study. The most common treatment-related adverse effect aside from the known AEs with docetaxel was transient fever/flu-like symptoms following PDS01ADC.

Enrollment in the trial is ongoing. The study is expected to reach completion by the end of 2026.³

Bedu-Addo concluded in the news release, "We are encouraged by the progression-free survival and PSA declines observed in this difficult-to-treat population and remain focused on advancing PDS01ADC as a key component of our immuno-oncology pipeline."

REFERENCES

1. Abel ML, Warner A, Donahue R, et al. Docetaxel and the Tumor Targeting Interleukin-12 (IL-12) PDS01ADC in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC). Cancer Res. 2026;86(2_suppl). PR008. doi: 10.1158/1538-7445.PROSTATECA26-PR008

2. PDS Biotech announces presentation of preliminary results from phase 2 study of IL-12 tumor targeted immunocytokine (PDS01ADC) in 3rd line metastatic castration resistant prostate cancer by the NCI. News release. PDS Biotechnology Corporation. January 28, 2026. Accessed January 28, 2026. https://www.pdsbiotech.com/index.php/investors/news-center/press-releases/press-releases1/132-2025-news/1029-pds-biotech-announces-presentation-of-preliminary-results-fr2026-01-28-055002

3. M9241 in combination with docetaxel in adults with metastatic castration sensitive and castration resistant prostate cancer. ClinicalTrials.gov. Last updated January 16, 2026. Accessed January 28, 2026. https://clinicaltrials.gov/study/NCT04633252