Abstract PR008: Docetaxel and the Tumor Targeting Interleukin-12 (IL-12) PDS01ADC in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)

Abstract Background: Although immune checkpoint inhibitors have not demonstrated clinical efficacy in unselected prostate cancer patients, there is a rationale to explore other immunotherapy strategies, including those that can activate natural killer (NK) cells. PDS01ADC is a tumor-targeting IL-12 that recognizes DNA-histone epitopes exposed on necrotic regions of tumors Preliminary clinical data have demonstrated the ability to activate NK and associated cytokines in prostate cancer patients (pts). Furthermore, in a small cohort, PDS01ADC treatment was associated with PSA declines. (Meininger, ASCO GU 2022) Preclinical modeling suggested therapeutic synergy between PDS01ADC and docetaxel. (Franks, Cancer Immunol Immunother 2023) These data provided the rationale for clinical trial NCT04633252. Phase 1 data at 3 doses of PDS01ADC demonstrated preliminary evidence of immune synergy, regardless of dose level. Herein, we present preliminary data from all mCRPC pts enrolled on the phase 1 and 2 portions of NCT04633252. (Madan, Cytokines 2023) Methods: NCT04633252 is an ongoing Phase I/II study enrolling up to 24 pts with mCRPC with progressive disease following prior therapy including androgen deprivation and an androgen pathway inhibitor. Participants in the phase 2 portion are treated with standard-of-care docetaxel (75 mg/m2 every 3 weeks) with the addition of PDS01ADC at a dose of 12 mcg/kg, given as a subcutaneous injection with each cycle of chemotherapy starting with cycle 2. The primary endpoint of the single arm, phase 2 study is to increase expected median progression free survival (PFS) on docetaxel from 4. 5 months (mo) to 9 mo with the addition of PDS01ADC. Results: Thus far, 16 mCRPC pts have enrolled on both the phase 1 and 2 portions of the study with a median age of 68 (range: 45-82) and a median baseline PSA of 150 ng/dL (range: 14. 2-2251 ng/dL). All pts were previously treated with enzalutamide and/or abiraterone acetate, and 6/16 pts had previous docetaxel in the castrate-sensitive setting. The median PFS of these mCPRC pts is 9. 6 mo (range: 4. 3 to 32. 2 mo). The median PSA response was a 40% decrease from pre-treatment baseline, with 13/16 pts experiencing a PSA decline and 6/16 pts with a 50% PSA decline. Treatment has been well-tolerated with expected adverse events consistent with phase 1 results, without new safety signals. The most common treatment-related adverse event, beyond known docetaxel side effects, is transient fever/flu-like symptoms following PDS01ADC. Discussion: The preliminary data from the NCT04633252 study suggest that the combination of docetaxel and PDS01ADC is tolerable with emerging evidence of activity in mCRPC. This trial continues to enroll at the National Cancer Institute (NCI), Bethesda, MD. Additional NCI studies are also exploring cytokine-based strategies that can impact the pleiotropic tumor immune microenvironment in prostate cancer. Citation Format: Melissa Lauren. Abel, Aanika Warner, Renee Donahue, Yo-ting Tsai, Jennifer Marte, Ruchi Patel, Lisa Cordes, Megan Hausler, Amy Hankin, Nikki Williams, Philip Arlen, William D. Figg, James Hodge, Jeffrey Schlom, James Gulley, Fatima Karzai, Ravi Madan. Docetaxel and the Tumor Targeting Interleukin-12 (IL-12) PDS01ADC in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC) abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86 (2Suppl): Abstract nr PR008.