Allocetra Plus Chemotherapy Receives Green Light to Continue Investigation in Solid Tumors With Peritoneal Metastasis

The phase 1/2 trial (NCT05431907) evaluating the addition of Allocetra to standard chemotherapy administered via pressurized intraperitoneal aerosol chemotherapy (PIPAC) received regulatory clearance to continue evaluation and launch the dose-escalation cohort in patients with advanced-stage peritoneal metastasis arising from solid tumors following the completion of an interim data review by an Independent Data and Safety Monitoring Board (DSMB) and the Israeli Ministry of Health (IMOH).¹

With the exception of a protocol amendment, in which patients in the dose-escalation cohort will receive a higher starting dose of Allocetra following the DSMB’s recommendation, the study will continue as planned. Earlier, the company received IMOH clearance for its phase 1/2 trial (NCT05581719) evaluating Allocetra alone or in combination with PD-1 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, in which no deaths or DSMB-identified safety signals occurred.

“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,” Einat Galamidi, MD, medical vice president of Enlivex, stated in a press release.

Allocetra is a universal, off-the-shelf cellular therapy designed to reprogram macrophages into their homeostatic state. Non-homeostatic macrophages, which are generated in solid cancers, sepsis, and other diseases, influence the severity of each disease. By restoring macrophage homeostasis, Allocetra may provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications.

In November 2022, the FDA cleared an investigational new drug (IND) application to study Allocetra in patients with advanced solid malignancies. The IND was based on preclinical studies conducted in collaboration with Yale Cancer Center that showed a statistically significant improvement in survival when Allocetra was combined with a PD-1 inhibitor in a murine model of ovarian cancer, as well as a PD-1 or CTLA-4 inhibitor in a murine model of peritoneal mesothelioma.²

The open-label, dose-escalation and -expansion trial is expected to enroll approximately 12 patients across four cohorts.1 The primary objective in the first patient cohort was to establish the safety profile of the agent. The agent is given once every six weeks in combination with chemotherapy delivered to the peritoneum. The dose and schedule of chemotherapy will be left to the treating physician. 

The study was designed to first evaluate the maximum feasible dose of Allocetra in two intra-patient and intra-cohort dose-escalation cohorts, followed by two additional cohorts comparing the selected dose of Allocetra both before and after chemotherapy. Chemotherapy will be delivered through PIPAC, which is typically used when patients are not eligible to receive standard therapy due to large tumor bulk, large volume of persistent ascites, or other circumstances.

The primary end point of the study is the number and severity of Allocetra-related adverse effects (AEs) and serious AEs during the 16-week assessment period, which will begin after the first dose of treatment is administered. Secondary end points include 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 evaluated as exploratory end points.

References

1. Enlivex receives positive DSMB recommendation and IMOH clearance to continue phase I/II trial of Allocetra combined with chemotherapy in patients with peritoneal metastases arising from solid cancers. News release. Enlivex Therapeutics. March 20, 2023. Accessed March 20, 2023. https://enlivex.com/investor-relations/#latest-news
2. Enlivex Receives Allocetra IND Clearance From The U.S. Food And Drug Administration For Treatment Of Patients with Advanced Solid Malignancies. News release. Enlivex Therapeutics. November 28, 2022. Accessed March 20, 2023. https://www.globenewswire.com/en/news-release/2022/