PDS01ADC in Combination With Hepatic Artery Infusion Pump (HAIP) and Systemic Therapy for Subjects With Metastatic Colorectal Cancer, Intrahepatic Cholangiocarcinoma, or Metastatic Adrenocortical Carcinoma

Adrenal Cortex Neoplasms, Adrenal Cortical Carcinoma, Adrenal Gland Cancer, Adrenal Gland Neoplasms, Adrenocortical Carcinoma (ACC), Bile Duct Cancer, Bile Duct Neoplasms, Cholangiocarcinoma, Colorectal Cancer, Colorectal Neoplasms, Intrahepatic Bile Duct Cancer, Intrahepatic Cholangiocarcinoma (Icc), Metastatic Colorectal Cancer (Mcrc)

Unresectable Liver Tumor, SMART System, Response Rates, Progression Free Survival (Pfs), Patient Survival, Overall Survival (Os), NHS-IL12, Mcrc, Icc, ACC

Background: One way to treat liver cancer is to deliver chemotherapy drugs only to the liver (and not to the whole body). Researchers want to see if adding the drug PDS01ADC can improve the treatment. The drug triggers the immune system to fight cancer.\<TAB\> Objective: To see if treatment with HAIPs to deliver liver-directed FUDR and Dexamethasone chemotherapy in combination with PDS01ADC is effective for certain cancers. Eligibility: People aged 18 and older who have cancer of the bile ducts that is only in the liver, or colorectal cancer that has spread to the liver, or cancer of the adrenal glands that has spread to the liver, who are also receiving or planning to receive standard systemic chemotherapy for their disease. Design: Participants will be screened with: Medical history Physical exam Blood tests Pregnancy test (if needed) Tumor biopsy (if needed) Electrocardiogram Computed tomography (CT) scans Participants will have an abdominal operation. A catheter will be placed into an artery that feeds blood to the liver. The catheter will then be attached to the HAIP. The HAIP will lay under the skin on the left side of the abdomen. All participants will have liver-directed FUDR and Dexamethasone chemotherapy drugs or heparin with saline infused into the HAIP every 2 weeks. PDS01ADC will be injected under the skin every 4 weeks. They will receive this treatment until their cancer gets worse or they have bad side effects. Participants will also receive standard systemic chemotherapy for their disease, assigned based on diagnosis, through an IV by their medical oncologist (at NIH or by a local provider) every 2 weeks. Participants will have 2 study visits at NIH each month. They will have CT scans every 8 weeks. At visits, they will repeat some screening tests. Participants will have a follow-up visit 1 month after treatment ends. Then they will be contacted every 6 months for 5 years.

Background: Regional chemotherapy for hepatic malignancies takes advantage of the fact that tumors are perfused almost exclusively by the hepatic artery and, that the agent used (Floxuridine, FUDR) has a 95% first-pass metabolism by the liver. Early clinical trials performed during the 1970's and 1980's demonstrated impressive response rates that led to the adoption of hepatic artery infusion pump chemotherapy (HAIP) at select centers; however, little has changed in the ensuing decades with respect to regional therapy for the liver, although there has been continued and even renewed interest. Dose reductions of FUDR are common after several treatments, which has limited both the magnitude and duration of treatment responses in many cases. We posit that the logical and much-needed "next step" in regional therapy is to take advantage of the FUDR-induced tumor necrosis with an agent able to activate local tumor immunity for a synergistic effect. PDS01ADC is an immunocytokine composed of two IL-12 heterodimers, each fused to the H-chain of the NHS76 antibody. The NHS76 IgG1 antibody has affinity for both single- and double-stranded DNA (dsDNA), and targets regions of tumor necrosis where DNA has become exposed. PDS01ADC targets necrotic areas of the tumor and activates immune cells in the tumor microenvironment to induce a Th1 polarization of lymphocytes and the release of IFN-gamma. IFN-gamma in turn induces a host of immunomodulatory effects that contribute to robust antitumor responses that are localized within the tumor microenvironment, with no systemic distribution or exposure to IL-12. Data from a recent Phase I study demonstrate that subcutaneous administration of PDS01ADC is safe and a MTD has been determined. Moreover, preclinical models indicate that PDS01ADC synergizes with therapies able to effectively induce tumor necrosis, which may also minimize toxicity by limiting off-target exposure. Objective: -To determine the objective response rate (ORR) in participants with unresectable metastatic colorectal cancer (mCRC), intrahepatic cholangiocarcinoma (ICC), or adrenocortical carcinoma (ACC) with liver dominant disease treated with PDS01ADC in combination with HAIP in participants receiving systemic therapy Eligibility: * Histologically or cytologically confirmed, unresectable, colorectal adenocarcinoma metastatic to the liver (Cohort 1), intrahepatic cholangiocarcinoma (Cohort 2) or adrenocortical carcinoma with liver dominant disease (Cohort 3) * No evidence of extrahepatic metastases * Participants must have received first-line systemic chemotherapy. * Age \>= 18 years Design: -Open label, single center, non-randomized Phase II study

United States