On August 16, 2022 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company, reported that the Israeli Ministry of Health (MOH) authorized the initiation of a company-sponsored Phase I/II clinical trial designed to evaluate the safety, tolerability and preliminary efficacy of Allocetra alone, and in combination with a PD1 checkpoint inhibitor, in patients with advanced solid tumors (Press release, Enlivex Therapeutics, AUG 16, 2022, View Source [SID1234618454]).
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Einat Galamidi, M.D., Vice President, Medical of Enlivex, stated, "With Allocetra treatment, we aim to change the balance of macrophage populations surrounding the solid tumor environment in favor of anti-cancer activity in order to overcome the biological mechanisms underlying checkpoint inhibitor resistance. Collaborative studies with Yale Cancer Center have generated meaningful preclinical data, suggesting we may be successful in these efforts, with Allocetra and an anti-PD1 agent synergistically combining, which delivered a statistically significant survival benefit in a murine model of ovarian cancer. We aim to build on these results in our upcoming Phase I/II trial and are pleased that the Israeli Ministry of Health has cleared it for initiation."
The planned Phase I/II trial is a multicenter, open-label, dose escalation trial that is expected to enroll up to 48 patients with advanced solid tumors across two trial stages. Stage 1 of the trial will examine escalating doses of Allocetra monotherapy administered intravenously (IV) or intraperitoneally (IP) once a week for three consecutive weeks. Stage 2 will evaluate escalating doses of Allocetra administered IV or IP and combined with anti-PD1 therapy. Patients in Stage 2 will receive three injections of Allocetra concomitantly with the studied anti-PD1 agent. The primary objective of the study is to evaluate safety and tolerability throughout the treatment period and through one week after the last administration of Allocetra. Key secondary endpoints include efficacy assessments, such as best overall response rate, progression-free survival, and overall survival. Changes in immune cell/cytokine profiling in peritoneal fluid will also be assessed as an exploratory endpoint.
The planned study population will be adult patients with advanced, unresectable or metastatic solid tumors that have relapsed or have been refractory to available approved therapies, or patients who are not eligible for, or have declined additional standard-of-care systemic therapy.
Though commercially successful, checkpoint inhibitors have limited efficacy in many cancers, with a 2019 study estimating less than 13% of all U.S. cancer patients responded to these therapies1. This limited efficacy of checkpoint inhibitors in certain solid cancers is linked to tumor mechanisms that facilitate the recruitment of macrophages which become "pro-tumor" tumor associated macrophages (TAMs). The TAMs typically form a physical layer on top of the solid tumor and induce immunosuppression in the solid tumor microenvironment. This hampers the ability of immune cells, which are the effectors of checkpoint inhibitor therapy, to efficiently attack the tumor cells. Moreover, TAMs promote tumor growth and metastasis through various additional mechanisms that contribute to poor clinical outcomes and response to therapy. Previously reported preclinical data from solid tumor models suggest that Allocetra has the potential to reprogram pro-tumor macrophages back to their homeostatic state and may thereby promote disease resolution and enhance the efficacy of checkpoint inhibitors and other immunotherapeutic agents.
REFERENCE
1. Haslam A, Prasad V. Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs. JAMA Netw Open. 2019 May 3;2(5):e192535. doi: 10.1001/jamanetworkopen.2019.2535. PMID: 31050774; PMCID: PMC6503493.
ABOUT ALLOCETRA
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.