Tumor-Targeted IL-12 (PDS01ADC) with Hepatic Artery Infusion Pump Therapy for Colorectal Liver Metastases: Interim Analysis of a Non-randomized Phase II Trial.

Abstract

Most patients with metastatic colorectal cancer have microsatellite stable or mismatch repair-proficient tumors, which are resistant to immunotherapy especially in cases of liver metastases. We sought to determine if tumor-targeted interleukin-12 (PDS01ADC) can improve outcomes for patients with colorectal cancer liver metastases managed with hepatic artery infusion pump (HAIP) chemotherapy. NCT05286814 is a phase II non-randomized trial evaluating subcutaneous PDS01ADC in combination with HAIP floxuridine and systemic chemotherapy (FOLFOX or FOLFIRI) in patients with unresectable microsatellite stable or mismatch repair-proficient colorectal liver metastases previously treated with at least one line of systemic chemotherapy. Primary endpoints for the planned interim analysis were overall response rate and safety. Nine patients were included in this planned interim analysis. 78% (7/9) of patients receiving PDS01ADC with HAIP therapy had partial or complete responses at 6 months. Median hepatic progression-free survival for patients receiving PDS01ADC + HAIP therapy was 12.7 months with minimum follow-up of 13.1 months. Grade ≥3 toxicities occurred in 78% but were manageable and did not limit HAIP therapy. No patients developed a biliary stricture within 6 months of initiating treatment. Clinical responders to PDS01ADC demonstrated enhanced peripheral immune activation, including elevated levels of circulating T cell subsets with stem-like features, and increased CD8+ T cell:T regulatory cell ratio in tissue biopsies. 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 endpoints.