Tumor-Targeted IL-12 Plus HAIP Chemo Shows Promise for CRC With Liver Metastases

Combining the tumor-targeted interleukin-12 immunocytokine PDS01ADC with hepatic artery infusion pump (HAIP) chemotherapy elicited strong antitumor activity in patients with microsatellite stable or mismatch repair–proficient metastatic colorectal cancer with liver metastases, according to data from a phase 2 trial (NCT05286814) published in JCO Oncology Advances.^1,2

Findings of an interim analysis from a stage 1 of a nonrandomized phase 2 trial showed an objective response rate (ORR) of 77.8% (7 of 9 patients) by RECIST v1.1 at 6 months among patients who received PDS01ADC plus HAIP-delivered floxuridine.¹ The robust ORR observed with the combination was considerably higher than the 35% (7 of 20 patients) ORR previously observed with HAIP chemotherapy alone in a similar trial. However, no head-to-head comparison has been conducted at this point.

The 24-month survival rate with the PDS01ADC combination was approximately 85%, compared with roughly 40% in with HAIP-only in the parallel trial. Extrahepatic progression-free survival (PFS) had not been reached at a minimum follow-up of 13.1 months with the PDS01ADC combination; the parallel trial showed a median PFS of 8.1 months with HAIP alone.¹ 

Over three-fourths (78%) of patients had grade ≥3 toxicities, but they were manageable and did not lead to reduction of HAIP therapy. There were no cases of biliary stricture in the first 6 months following the start of treatment.

“Addition of PDS01ADC is not detrimental to HAIP therapy and is associated with both systemic and intratumoral immune modulation. Initial results warrant continuation to full enrollment for further evaluation of clinical and scientific end points,” wrote the clinical trial authors, who were led by Jonathan Hernandez, MD, investigator in the Surgical Oncology Program at the National Cancer Institute.²

Trial Design and Patient Characteristics

Overall, the phase 2 trial explored PDS01ADC in combination with HAIP floxuridine and systemic chemotherapy (leucovorin, 5-fluorouracil, and oxaliplatin or leucovorin, 5-fluorouracil, and irinotecan) in patients with unresectable microsatellite stable or mismatch repair-proficient colorectal liver metastases that had previously been treated with a minimum of 1 line of systemic chemotherapy. The primary end points for the planned interim analysis were ORR and safety.

The 9-patient cohort receiving the combination of PDS01ADC and HAIP had a median age of 47 years (range, 31-58). The group was composed of 5 men and 4 women. In terms of racial background, 77.8% of participants were White, while the race for the remaining 22.2% was unknown or not reported. Ethnicity data indicated that 77.8% were not Hispanic or Latino, while 22.2% identified as Hispanic or Latino.

Regarding their oncological history, all 9 patients had previously undergone systemic chemotherapy with 5-FU and oxaliplatin, and 33.3% had received prior irinotecan. Furthermore, 77.8% of the cohort had been treated with bevacizumab (Avastin), but none had received prior immunotherapy.

At the time of HAIP surgery, 14.3% of the patients were found to have positive regional lymph nodes. Genetic profiling of the tumors revealed that 44.4% carried a pathogenic mutation in KRAS, while 11.1% had a BRAF mutation. Notably, all 9 patients in this treatment arm had microsatellite stable disease.

“HAIP was approved by the FDA in 2024 and is gaining prominence at leading oncology centers. Despite many meaningful advances in oncology, metastatic colorectal cancer remains an area of significant unmet need. These early results showing strong tumor response rates and promising patient survival are encouraging and support our approach of subcutaneously administering PDS01ADC to activate the immune system against the cancer,” Frank Bedu-Addo, PhD, president and chief executive officer of PDS Biotech, stated in a news release.¹ “We believe these findings represent a meaningful step toward more precise immune-based treatments without the significant side effects that have historically limited traditional recombinant cytokine therapies.”

REFERENCES

1. PDS Biotechnology Corporation. PDS Biotech announces publication of positive PDS01ADC interim phase 2 clinical trial data from stage 1 of NCI-led metastatic colorectal cancer (mCRC) trial. News release. April 15, 2026. https://tinyurl.com/3y4dzvxp

2. Hernandez J, et al. Tumor-targeted IL-12 (PDS01ADC) with hepatic artery infusion pump therapy for colorectal liver metastases: interim analysis of a nonrandomized phase II trial. JCO Oncol Adv. 2026;3:e2500173. ascopubs.org/journal/jcoa