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: Not yet recruiting
• Trial end date: 2028-12-31

Summary

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-gamma. IFN-gamma 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 subjects with unresectable metastatic colorectal cancer (mCRC) and intrahepatic cholangiocarcinoma (ICC) treated with M9241 in combination with HAIP 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

• Subjects must have received first-line systemic chemotherapy.

• Age >= 18 years.

Design:

-Open label, single center, non-randomize Phase II study

• Phase: Phase 2

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Dexamethasone; Floxuridine; Fluorouracil; Gemcitabine; Irinotecan; Leucovorin; Oxaliplatin