PDS Biotechnology Targets Phase III Trial for PDS0301 in Metastatic Colorectal Cancer

Key Points

• PDS Biotechnology plans to advance PDS0301 into a Phase III trial for heavily pretreated metastatic colorectal cancer with liver metastases, targeting a trial start around the first quarter of 2027 after submitting a protocol to the FDA.
• In an NCI-led Phase II study combining PDS0301 with hepatic artery infusion therapy, the company reported that the treatment was well tolerated and appeared to produce more durable responses, including a reported six-month objective response rate above 70% versus 35% for the comparator cohort.
• PDS0301 is designed to deliver IL-12 directly to tumors while limiting the systemic toxicity associated with traditional IL-12 treatments; the company expects additional data from multiple cancer programs over the next six to 18 months.

PDS Biotechnology NASDAQ: PDSB outlined plans to advance its investigational immunocytokine PDS0301 into a Phase III study for heavily pretreated metastatic colorectal cancer with liver metastases, following discussions with the U.S. Food and Drug Administration and clinical findings from a National Cancer Institute-led study.

During a virtual key opinion leader event, Chief Executive Officer Frank Bedu-Addo said PDS0301 is designed to deliver interleukin-12, or IL-12, to tumors. The treatment fuses two IL-12 molecules to the NHS76 antibody, which binds to DNA released by damaged or dying cells. The company’s premise is that chemotherapy-induced tumor damage creates binding sites that may help localize IL-12 in tumors while limiting the systemic inflammatory toxicity historically associated with recombinant IL-12.

Bedu-Addo said PDS0301 is administered through a subcutaneous injection and has been used in nearly 400 patients at the National Cancer Institute, where it has been “well-tolerated” without the high toxicities traditionally associated with IL-12, according to the company.

Unmet Need in Metastatic Colorectal Cancer

Chief Medical Officer Kirk Shepard said colorectal cancer represented about 1.9 million new cases and 900,000 deaths globally in 2022. He noted that patients with metastatic disease who have proficient mismatch repair or microsatellite-stable tumors account for roughly 95% of metastatic colorectal cancers and generally do not respond to immunotherapy.

Liver metastases occur in about half of patients with metastatic colorectal cancer and are a major contributor to morbidity and mortality, Shepard said. He also cited trial benchmarks showing that objective response rates decline substantially with successive treatment lines, falling to roughly 1% to 6% in the third-line setting.

Shepard said controlled third- and fourth-line studies have produced an average objective response rate of about 2.5% in experimental arms and median overall survival of 7.9 months, though he cautioned that cross-trial comparisons are descriptive and patient populations differ.

NCI Study Combined PDS0301 With Hepatic Artery Infusion

Jonathan Hernandez, chief of the Surgical Oncology Section at the National Cancer Institute, reviewed an ongoing Phase II study evaluating PDS0301 with hepatic artery infusion pump therapy in patients with colorectal cancer liver metastases.

Hepatic artery infusion pump therapy uses floxuridine, a chemotherapy drug administered directly to the hepatic artery through an implanted pump. Hernandez said liver tumors are supplied primarily by arterial blood, while much of the normal liver is supported by portal venous blood flow. The approach permits substantially higher local exposure to floxuridine than systemic administration, he said.

Hernandez described the PDS0301 study as sequential and non-randomized. An earlier cohort included 20 patients receiving hepatic artery infusion pump therapy, while the subsequent cohort added PDS0301 and enrolled 22 patients. He said the patients were heavily pretreated, with many having previously received oxaliplatin and irinotecan.

According to Hernandez, adding PDS0301 did not reduce the amount of floxuridine patients could receive. The combination was also “super well-tolerated,” he said, with manageable diarrhea the principal notable toxicity. He said the study did not show increased damage to the biliary system, a concern because the hepatic artery supplies the bile ducts.

At three months, Hernandez said both the pump-only and PDS0301 combination cohorts showed substantial tumor responses. By six months, however, he said patients receiving PDS0301 appeared to have more durable responses and less disease progression. Bedu-Addo said there were no complete responses at three months but three complete responders at six months in the PDS0301-treated group.

In a later discussion, company executives cited objective response rates above 70% at six months for patients receiving PDS0301, compared with 35% for the comparator cohort. Hernandez said updated survival data will be presented at the Society of Surgical Oncology annual meeting in March, followed by publication of full results and spatial transcriptomic analyses.

Phase III Planning and Regulatory Discussions

Shepard said the company has held discussions with the FDA regarding the proposed Phase III trial’s design and endpoints. He said the agency’s feedback did not prevent the company from moving forward, and PDS Biotechnology plans to submit a protocol to the FDA during the current quarter.

The proposed study is expected to include a small third arm to address the contribution of treatment components, Bedu-Addo said. Potential endpoints under consideration include objective response rate, progression-free survival and overall survival. Shepard said the company expects the study will not need to be large because of the response-rate differences observed in the earlier study, and management is targeting a trial start around the first quarter of 2027.

Hernandez said enrollment could be supported by the growing adoption of hepatic artery infusion pump therapy at cancer centers and by the limited treatment options available after patients have received oxaliplatin and irinotecan. Bedu-Addo added that the company believes sites participating in an ongoing national ECOG hepatic artery infusion study could provide familiarity with the procedure for a later-line PDS0301 trial.

The company said it has Phase III drug supply available and expects to report maturing results from PDS0301 programs across several tumor types over the next six to 18 months.

About PDS Biotechnology (NASDAQ:PDSB)

PDS Biotechnology Corporation NASDAQ: PDSB is a clinical-stage biopharmaceutical company focused on developing targeted immunotherapies for cancer and infectious diseases. The company's technology is designed to stimulate the immune system and generate antigen-specific T-cell responses against diseased cells.

PDS Biotech's lead investigational product is PDS0101, an immunotherapy designed to target human papillomavirus type 16 (HPV16) antigens E6 and E7. The product is being evaluated in combination with other treatments for HPV16-associated cancers, including cervical, anal, and certain head and neck cancers.

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