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Allocetra Combination Therapy to Be Assessed in Solid Tumors

In an ovarian cancer mouse model, the combination therapy group showed an 83% increase in survival duration compared to an untreated group.

The Israeli Ministry of Health (MOH) has approved the initiation of a phase 1/2 clinical trial to investigate Enlivex’s Allocetra cell therapy, both alone and in combination with a PD-1 checkpoint inhibitor, for the treatment of solid tumors.1 

Allocetra is an investigational cell therapy intended to reprogram macrophages that have become "pro-tumor" tumor associated macrophages (TAMs) back into a homeostatic state. The therapy previously demonstrated promising results in a preclinical study conducted by Enlivex and Yale Cancer Center, data from which was presented at the American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL, June 3-7, 2022.2 In an ovarian cancer mouse model, the combination therapy group showed an 83% increase in survival duration compared to an untreated group. Additionally, the combination therapy group had a survival probability up to 50%, compared to 0% in the untreated group.

"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,” Einat Galamidi, MD, vice president, medical, Enlivex, said in a statement regarding the news.1 “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 1/2 trial and are pleased that the Israeli MOH has cleared it for initiation."

The preclinical study also demonstrated that Allocetra and an anti-PD1 inhibitor, administered as monotherapies, increased survival duration compared to untreated mice by 42% and 58% respectively.2 However, the 2 monotherapy groups did not display any significant difference in overall survival probability compared to the untreated group. The investigators who authored the poster on the preclinical study noted that Allocetra previously showed a positive safety profile in clinical trials for two other indications, sepsis and covid-19.3

"I am highly encouraged by these preclinical findings, which clearly demonstrate Allocetra's potential to address a long-standing unmet need,” Marcus Bosenberg, MD, PhD, professor of Dermatology, Pathology, and Immunobiology and director of the Center for Precision Cancer Modeling at Yale Cancer Center, said in a statement regarding the preclinical data published in May 2022.2 “The immunosuppressive microenvironments of ovarian tumors have limited the clinical benefits of checkpoint inhibition in this indication. Allocetra may reverse immunosuppressive tumor microenvironments and may ultimately improve patient outcomes by synergistically enhancing checkpoint inhibitor efficacy in clinical trials."

The multicenter, open-label, dose-escalation trial will seek to enroll up to 48 adult patients with advanced, unresectable, or metastatic solid tumors.1 Participants must be relapsed or refractory to available approved therapies or must be ineligible for or declined standard-of-care systemic therapy.

In the first stage, patients will receive Allocentra intravenously (IV) or intraperitoneally (IP) as a monotherapy. In the second stage, patients will receive Allocentra via IV or IP combined with anti-PD1 therapy. The primary end point is safety and tolerability, measured throughout the treatment period and through 1 week after the final dose of Allocentra. Secondary end points include best overall response rate, progression-free survival, and overall survival, and an exploratory end point will evaluate changes in immune cell and cytokine profiling in peritoneal fluid. The clinical trial is expected to begin by the end of 2022.2

REFERENCES
1. Enlivex receives Israeli Ministry of Health approval for the initiation of a phase I/II trial evaluating Allocetra alone and in combination with a PD1 checkpoint inhibitor in patients with advanced solid tumors. News release. Enlivex Therapeutics Ltd. August 17, 2022. https://www.globenewswire.com/news-release/2022/08/17/2499939/0/en/Enlivex-Receives-Israeli-Ministry-of-Health-Approval-for-the-Initiation-of-a-Phase-I-II-Trial-Evaluating-Allocetra-Alone-and-in-Combination-with-a-PD1-Checkpoint-Inhibitor-in-Patie.html 
2. Enlivex announces new preclinical data in ovarian cancer showing a substantial survival benefit when Allocetra is combined with PD-1 checkpoint inhibition at the American Society of Clinical Oncology (ASCO) annual meeting. News release. Enlivex Therapeutics Ltd. May 31, 2022. https://www.globenewswire.com/en/news-release/2022/05/31/2453221/0/en/Enlivex-Announces-New-Preclinical-Data-in-Ovarian-Cancer-Showing-a-Substantial-Survival-Benefit-when-Allocetra-is-Combined-with-PD-1-Checkpoint-Inhibition-at-the-American-Society-o.html
3. Mevorach D, Shabat Y, Regev E, Yalon E, Karbian N, Reicher B. In-vivo reprogramming macrophages and dendritic cells with Allocetra-OTS: Successful mono- and combination-antitumor therapy. J. Clin. Oncol. 2022;40(16_suppl):2532-2532. doi: 10.1200/JCO.2022.40.16_suppl.2532