M9241 in Combination With Hepatic Artery Infusion Pump (HAIP) and Systemic Therapy for Subjects With Metastatic Colorectal Cancer or Intrahepatic Cholangiocarcinoma

Colorectal Cancer Clinical Trial

Official title: Phase II Study Evaluating the Efficacy of M9241 in Combination With Hepatic Artery Infusion Pump (HAIP) and Systemic Therapy for Subjects With Metastatic Colorectal Cancer or Intrahepatic Cholangiocarcinoma

Status Recruiting

Clinical Trial Summary

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 M9241 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 chemotherapy in combination with M9241 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.

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.

Participants will have chemotherapy drugs or heparin with saline infused into the HAIP every 2 weeks. M9241 will be injected under the skin every 4 weeks. They will get systemic chemotherapy through an IV or mediport every 2 weeks. They will receive this treatment until their cancer gets worse or they have bad side effects.

Participants will have 2 study visits 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.

Clinical Trial Description

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.

M9241 (NHS-IL12) 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. M9241 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-y. IFN-y in turn induces a host of immunomodulatory effects that contribute to robust antitumor responses.

Data from a recent Phase I study demonstrate that subcutaneous administration of M9241 is safe and a MTD has been determined. Moreover, preclinical models indicate that M9241 synergizes with therapies able to effectively induce tumor necrosis, which may also

minimize toxicity by limiting off-target exposure.

Objective:

-To determine the overall response rates in participants with unresectable metastatic colorectal cancer (mCRC) and intrahepatic cholangiocarcinoma (ICC) treated with M9241 in combination with HAIP and systemic therapy.

Eligibility:

• Histologically or cytologically confirmed colorectal adenocarcinoma metastatic to the liver (Cohort 1) or unresectable intrahepatic cholangiocarcinoma (Cohort 2).

• 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 ;

Related Conditions & MeSH terms

• Bile Duct Cancer
• Bile Duct Neoplasms
• Cholangiocarcinoma
• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Colorectal Cancer (Mcrc)
• Neoplasms

• NCT number: NCT05286814
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Cathleen E Hannah, C.R.N.P.
• Phone: (240) 858-7006
• Email: cathleen.hannah@nih.gov
• Status: Recruiting
• Phase: Phase 2
• Start date: October 24, 2022
• Completion date: December 31, 2028