Novel Treatment with Intraperitoneal MOC31PE Immunotoxin in Colorectal Peritoneal Metastasis: Results From the ImmunoPeCa Phase 1 Trial
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Published on: February 10, 2023
Ida S Frøysnes1,2, Yvonne Andersson1, Stein G Larsen3
1Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Background:
MOC31PE immunotoxin was developed to rapidly kill cells expressing the tumor-associated epithelial cell adhesion molecule, which is highly expressed in colorectal cancer. Although cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may offer long-term survival to patients with peritoneal metastasis from colorectal cancer (PM-CRC), most patients experience disease relapse and novel therapeutic options are needed. On this basis, MOC31PE is being developed as a novel therapeutic principle to target PM-CRC.
Methods:
This was a dose-escalating phase I trial to evaluate the safety and toxicity (primary endpoint), pharmacokinetic profile, and neutralizing antibody response (secondary endpoints) upon intraperitoneal administration of MOC31PE in patients with PM-CRC undergoing CRS-HIPEC with Mitomycin C. Fifteen patients received the study drug at four dose levels (3+3+3+6), administered intraperitoneally as a single dose the day after CRS-HIPEC.
Results:
No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. There was negligible systemic absorption of the study drug. Drug concentrations in peritoneal fluid samples were in the cytotoxic range and increased in a dose-dependent manner. MOC31PE recovered from peritoneal cavity retained its cytotoxic activity in cell-based assays. All patients developed neutralizing antibodies.
Conclusions:
Intraperitoneal administration of MOC31PE was safe and well tolerated, and combined with low systemic uptake, MOC31PE seems ideal for local intraperitoneal treatment. The drug will be further evaluated in an ongoing phase II expansion cohort.
Insights
MOC31PE immunotoxin is a safe and well-tolerated treatment for peritoneal metastasis from colorectal cancer (PM-CRC). It shows promising local efficacy with minimal systemic absorption, warranting further investigation in phase II trials.
Area of Science:
- Oncology
- Immunotherapy
- Colorectal Cancer Research
Background:
- Colorectal cancer (CRC) with peritoneal metastasis (PM-CRC) has limited treatment options beyond surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).
- MOC31PE immunotoxin targets the epithelial cell adhesion molecule (EpCAM), highly expressed in CRC, offering a novel therapeutic strategy for PM-CRC.
Purpose of the Study:
- To evaluate the safety, toxicity, pharmacokinetics, and immunogenicity of intraperitoneal MOC31PE in patients with PM-CRC undergoing CRS-HIPEC.
- To determine the maximum tolerated dose (MTD) and assess MOC31PE's local activity within the peritoneal cavity.
Main Methods:
- A dose-escalating phase I clinical trial involving 15 patients with PM-CRC.
- MOC31PE was administered intraperitoneally as a single dose post-cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).
- Safety, toxicity, drug concentrations in peritoneal fluid, and systemic absorption were monitored.
Main Results:
- No dose-limiting toxicities were observed; the MTD was not reached.
- MOC31PE demonstrated negligible systemic absorption, with cytotoxic concentrations achieved in peritoneal fluid.
- Recovered MOC31PE retained its cytotoxic activity, and all patients developed neutralizing antibodies.
Conclusions:
- Intraperitoneal MOC31PE is safe and well-tolerated for PM-CRC treatment.
- Its low systemic uptake makes it suitable for local intraperitoneal therapy.
- Further evaluation in a phase II expansion cohort is ongoing.
