PDS Biotechnology Corporation announced that its investigational antibody-drug conjugate PDS01ADC has met predefined efficacy criteria in a Phase 2 clinical trial for metastatic colorectal cancer, triggering expansion to the second stage of enrollment. The milestone represents a significant advancement for the novel immunotherapy approach targeting one of the most challenging cancer types.
The National Cancer Institute-led study (NCT05286814) completed Stage 1 patient recruitment, achieving the pre-set RECIST v1.1 criteria required for expansion under the Simon two-stage design. At least 6 of 9 participants in the colorectal cancer cohort experienced an objective response, meeting the threshold for advancing to Stage 2 with enrollment expanding to a total of 22 participants.
Novel Mechanism Targets Tumor Necrosis
PDS01ADC represents a unique approach to IL-12 delivery, composed of two Interleukin-12 heterodimers fused to the NHS76 antibody. This antibody binds to both single- and double-stranded DNA, specifically targeting regions of tumor necrosis where DNA has become exposed. The design aims to deliver IL-12's potent anti-tumor effects directly to cancer sites while avoiding systemic exposure and associated toxicities.
"This novel investigational approach to the targeting and use of IL-12 results in little, or no systemic exposure to IL-12, and may allow patients to reap the benefits of cytokine therapy without the typical treatment-limiting toxicities," said Frank Bedu-Addo, PhD, President and Chief Executive Officer of PDS Biotech.
Addressing Critical Unmet Need
The advancement comes as colorectal cancer remains a leading cause of cancer mortality globally. According to the World Health Organization, more than 930,000 deaths were attributed to colorectal cancer worldwide in 2020. In the United States, over 150,000 new cases are diagnosed annually, with approximately 20% presenting as metastatic disease at diagnosis and an additional 25% of initially localized cases eventually progressing to metastatic disease.
The American Cancer Society identifies colorectal cancer as the second leading cause of cancer-related deaths in the United States, underscoring the urgent need for more effective treatment options.
Multi-Cohort Study Design
The open-label, single-center, non-randomized Phase 2 study includes three cohorts: metastatic colorectal cancer, cholangiocarcinoma, and adrenocortical cancer. Dr. Jonathan Hernandez, Chief of the Surgical Oncology Section at the NCI's Center for Cancer Research, leads the investigation.
The colorectal cancer cohort receives PDS01ADC administered systemically in combination with floxuridine (FUDR) delivered via hepatic artery infusion pump (HAIP). While the colorectal cancer cohort advances to Stage 2, the cholangiocarcinoma and adrenocortical cancer cohorts continue enrolling in Stage 1.
Timeline and Development Pipeline
PDS Biotech anticipates completing patient recruitment for the metastatic colorectal cancer cohort by the fourth quarter of 2025. The study operates under the company's collaborative research and development agreement with the NCI.
Beyond colorectal cancer, PDS01ADC is being evaluated in multiple Phase 2 trials across various cancer indications in combination with standard-of-care treatments. The company's broader pipeline includes Versamune® HPV, its lead investigational targeted immunotherapy being developed for advanced HPV16-positive head and neck squamous cell cancers, both as a combination therapy with immune checkpoint inhibitors and in a triple combination that includes PDS01ADC.
