PDS01ADC Shows Early Benefit in Metastatic Colorectal Cancer

A novel immunotherapy approach using PDS01ADC has demonstrated early results in patients with metastatic colorectal cancer (mCRC), particularly those with liver metastases who have progressed after prior treatment. Interim findings from a phase 2 clinical trial led by the National Cancer Institute (NCI) showed high response rates and promising survival outcomes, suggesting the treatment may help address a longstanding unmet need in this patient population.

The therapy, when combined with hepatic artery infusion pump (HAIP) chemotherapy, appeared to enhance the immune system’s ability to recognize and attack cancer cells. These findings, although based on a small group of patients, highlight the potential of combining targeted immunotherapy with regional chemotherapy delivery to improve outcomes.

PDS01ADC demonstrates response rates in early study

In the first stage of the phase 2 trial, which included nine patients with metastatic colorectal cancer and liver metastases, treatment with PDS01ADC plus HAIP chemotherapy resulted in an objective response rate (ORR) of 77.8% at six months.

This response rate is notably higher than what has been observed in a parallel study using HAIP therapy alone, where the ORR was approximately 35%.
Survival outcomes were also encouraging. Approximately 85% of patients treated with the combination therapy were alive at two years, compared with approximately 40% in the parallel study without PDS01ADC.

Additionally, extrahepatic progression-free survival — meaning the time before cancer spread outside the liver — had not yet been reached at a minimum follow-up of 13.1 months. In contrast, the comparable group without PDS01ADC experienced a median progression-free survival of 8.1 months.

Together, these findings suggest that adding PDS01ADC may enhance both tumor response and disease control.

Immunotherapy approach targets hard-to-treat mCRC

Metastatic colorectal cancer remains difficult to treat, particularly in patients with microsatellite stable (MSS) or proficient mismatch repair (pMMR) disease. Approximately 95% of patients fall into this category, and these tumors have historically shown limited response to immune checkpoint inhibitors.

PDS01ADC is a tumor-targeted IL-12 immunocytokine designed to activate the immune system directly within the tumor microenvironment. By delivering IL-12 — a potent immune-stimulating molecule — to the tumor site, the therapy aims to boost anti-tumor immune responses without causing widespread systemic toxicity.

When combined with HAIP therapy, which delivers chemotherapy directly to the liver through an implanted pump, this approach may create a more effective and localized attack on cancer cells.

Addressing an unmet need in liver metastases

Patients with metastatic colorectal cancer that has spread to the liver often face limited treatment options after first-line therapies stop working. Although systemic chemotherapy remains a standard approach, outcomes are often poor once the disease progresses.

HAIP therapy has gained increasing attention and was approved by the U.S. Food and Drug Administration in 2024. It allows for high concentrations of chemotherapy to be delivered directly to liver tumors, potentially improving local disease control.

However, even with this approach, many patients experience disease progression, highlighting the need for additional strategies to improve response rates and survival.

The addition of immunotherapy, such as PDS01ADC, represents an effort to enhance the effectiveness of existing treatments by engaging the immune system.

Phase 2 trial design and treatment approach

The ongoing phase 2 trial is an open-label, single-center, non-randomized study using a Simon two-stage design.

The study includes multiple cohorts, including patients with metastatic colorectal cancer, cholangiocarcinoma, and adrenocortical cancer. The current findings focus on the colorectal cancer cohort.

Patients received subcutaneous injections of PDS01ADC in combination with floxuridine (FUDR), delivered via HAIP therapy. The primary goal of the study is to evaluate tumor response, although additional outcomes such as survival and immune response markers are also being assessed.
The trial enrolled patients with metastatic colorectal cancer involving the liver who had previously received at least one line of chemotherapy and experienced disease progression.

This group represents a particularly challenging population, as treatment options are limited and prognosis is often poor after standard therapies fail.
By focusing on patients with MSS or pMMR disease, the study addresses a majority of individuals with metastatic colorectal cancer who typically do not benefit from currently available immunotherapies.

Early results support further study

Although the results are based on a small number of patients and no head-to-head randomized comparison has been conducted, the findings provide a strong rationale for continued investigation.

The study has already progressed beyond Stage 1, with plans to enroll additional patients to further evaluate the safety and effectiveness of the treatment.

Researchers also reported that the combination therapy appears to enhance immune activation, which may contribute to the improved clinical outcomes observed.

If these findings are confirmed in larger studies, PDS01ADC could represent a new therapeutic option for patients with metastatic colorectal cancer, particularly those with liver metastases who have limited alternatives after prior treatment.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

References

1. “PDS Biotech Announces Publication of Positive PDS01ADC Interim Phase 2 Clinical Trial Data from Stage 1 of NCI-led Metastatic Colorectal Cancer (mCRC) Trial,” by PDS Biotechnology Corporation. News Release; April 15, 2026.

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