Study protocol: targeted delivery of interleukin-12 in combination with hepatic artery infusion pump therapy for patients with adrenocortical carcinoma liver metastases.

Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy often detected at an advanced stage with limited effective treatment options beyond first-line chemotherapy. The liver is a common site of metastasis, and patients frequently present with substantial hepatic disease burden that precludes complete resection. Locoregional therapies, including hepatic artery infusion pump (HAIP) delivery of floxuridine, have not been thoroughly evaluated for treatment of ACC liver metastasis, likely due to its rare incidence and highly aggressive nature. PDS01ADC (previously referred to as NHS-IL12) is a novel antibody-drug conjugate designed to deliver the immunomodulatory cytokine interleukin-12 to areas of tumor necrosis and modulate the tumor microenvironment to support immune surveillance and cytotoxic tumor responses.

Combination of PDS01ADC with HAIP therapy (HAIP-delivered floxuridine plus systemic chemotherapy) was recently found to be feasible for clinical evaluation by an interim analysis in patients with colorectal liver metastases. Patients who received PDS01ADC with HAIP therapy had extended overall survival compared to patients who received HAIP therapy alone in a nonrandomized prior sequential study. We discuss herein the rationale and initiation of a new clinical trial arm to evaluate HAIP therapy with PDS01ADC for patients with ACC liver metastasis who have failed standard of care therapy. Patients with unresectable ACC liver metastasis and either resectable or no progressive extrahepatic disease will receive combination therapy including HAIP floxuridine and subcutaneous injection of PDS01ADC administered concurrently with systemic gemcitabine and oxaliplatin in 28-day cycles.

The primary outcome measured is overall response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria. Secondary outcomes measured in this study include intrahepatic and extrahepatic progression-free survival, overall survival, and safety of PDS01ADC combination therapy with HAIP-delivered floxuridine. For select patients with ACC liver metastasis, HAIP therapy with PDS01ADC may improve disease control and thereby prolong survival. Study ID NCT05286814 version 2026-05-04; https://clinicaltrials.gov/study/NCT05286814.

Adrenocortical carcinoma (ACC) is a highly lethal malignancy with few treatment options, especially in the setting of distant metastases. The liver is a common site of disease spread, with numerous metastases frequently limiting locoregional therapy options that specifically target the liver.

This study protocol describes the rationale for a new clinical trial arm for patients with ACC liver metastasis, evaluating high dose chemotherapy (HAIP floxuridine) delivered directly to the liver in combination with a targeted immunotherapy (PDS01ADC) designed to enhance immune responses within the tumor microenvironment. Combined with systemic chemotherapy (gemcitabine plus oxaliplatin), this approach leverages both liver-targeted and systemic (whole body) mechanisms to overcome treatment resistance and reduce tumor burden. The rationale to test this therapy for patients with ACC liver metastasis includes promising case studies using HAIP floxuridine for ACC liver metastasis as well as recent clinical data evaluating the safety and early efficacy of HAIP floxuridine combined with PDS01ADC in patients with colorectal liver metastases. It is important to expand this treatment evaluation to patients with ACC liver metastasis as this disease is highly aggressive with few options for effective treatment.