Enlivex Receives Positive DSMB Recommendation & IMOH Clearance to Continue Phase 1/2 Trial

Enlivex Therapeutics Ltd. recently announced an independent Data and Safety Monitoring Board (DSMB) has completed an interim data review for the first cohort of patients in the company’s ongoing Phase 1/2 clinical trial of Allocetra in patients with advanced-stage peritoneal metastasis arising from solid tumors as an add-on to the standard of care (SoC) chemotherapy administered via Pressurized Intraperitoneal Aerosol Chemotherapy (clinicaltrials.gov Identifier: NCT05431907). The Israeli Ministry of Health (IMOH) also reviewed the interim data and provided regulatory clearance to continue the study and open the study’s next cohort. In addition, the safety profile supported a protocol amendment to start new patients in the second cohort with higher initial doses of Allocetra. This IMOH clearance follows a previously-reported IMOH clearance to the company’s second Phase 1/2 clinical trial, which is evaluating Allocetra as monotherapy and in combination with anti-PD1 checkpoint inhibitors in patients with advanced-stage solid tumors.

The DSMB based its review on available safety data for the three enrolled patients in the first cohort, in which two patients received three escalating doses of Allocetra, and one received two escalating doses of Allocetra, once every 6 weeks as an add-on to SoC chemotherapy delivered to the peritoneum. The primary purpose of the dosing regimen for the first cohort was to establish a safety profile that may enable an increase in the Allocetra dosing level administered to additional patients in the study and potentially associate dose levels with indications of effect.

There were no mortalities nor DSMB-identified safety signals in the first cohort, and the DSMB recommended that the study continue to further dose escalation and additionally agreed to increase the starting dose of Allocetra in the next cohort. Following the DSMB recommendation, the IMOH reviewed the available safety data for the first cohort and provided regulatory clearance to initiate the recruitment of patients into the second cohort.

Einat Galamidi, MD, Medical Vice President of Enlivex, said “We are delighted with the safety profile of Allocetra when administered directly into the peritoneal cavity, as demonstrated in the first three patients in this trial. This is the first time Allocetra has been injected locally into the peritoneum cavity, a route of administration that may be relevant to various alternatives of local administration of Allocetra™ in different oncological indications.”

The Phase 1/2 trial is a company-sponsored, open-label, dose escalation and expansion trial that is expected to enroll a total of approximately 12 patients across four cohorts. It is designed to evaluate the safety and potential preliminary efficacy of Allocetra combined with SoC chemotherapy in patients with peritoneal metastases arising from solid cancer. The study begins with two cohorts of intra-patient and intra-cohort dose escalation to determine the maximum feasible dose (MFD) of Allocetra in this population, followed by two additional cohorts comparing administration of Allocetra at the selected dose either before or after administration of SoC via a pressurized intraperitoneal aerosol chemotherapy procedure (PIPAC; a technique applied when patients are not eligible to receive the standard treatment due to a considerable tumor load, large quantities of persistent ascites, or other circumstances).

Intraperitoneally delivered Allocetra and SoC chemotherapy administered via PIPAC will be given to patients every 6 weeks. Systemic chemotherapy will also be administered per the treating oncologist’s plan. The primary endpoint is the number and severity of Allocetra-related adverse events and serious adverse events during the 16-week assessment period, starting from the first administration of study treatment. Secondary endpoints include efficacy assessments, such as best overall response rate, progression-free survival, and overall survival. Changes from baseline in macrophage and immune cell characteristics in peritoneal fluid and tissues will also be assessed as an exploratory endpoint.

Allocetra is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as “unmet medical needs”, as a stand-alone therapy or in combination with leading therapeutic agents.

Enlivex is a clinical stage macrophage reprogramming immunotherapy company developing Allocetra, a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Resetting non-homeostatic macrophages into their homeostatic state is critical for immune system rebalancing and resolution of life-threatening conditions. For more information, visit  http://www.enlivex.com.