Enlivex, Beigene Collaborate To Test A New Combination Treatment To Fight Advanced-Stage Solid Tumors

This month, Enlivex Therapeutics Ltd. ENLV announced a new clinical collaboration agreement with Beigene Ltd BGNE to test a new combination treatment to fight advanced-stage solid tumors. The therapy will combine Allocetra, Enlivex’s novel macrophage reprogramming immunotherapy with tislelizumab, Beigene’s anti-PD-1 immune checkpoint inhibitor, with the goal of creating an even more potent cancer-fighting treatment than either immunotherapy on its own. 

Enlivex’s Updated Phase 1/2a Trial Will Add A Second Stage To Study The Allocetra- Tislelizumab Combination Therapy

Under the new agreement, Enlivex is amending its ongoing Phase 1/2a trial to now include tislelizumab in stage 2 of the clinical trial,  one that will evaluate Allocetra and tislelizumab as a combination therapy. 

The multicenter, open-label trial will enroll approximately 48 patients with advanced-stage solid tumors across both trial stages. They will each get three escalating doses of either Allocetra alone or the combined Allocetra and tislelizumab.

The ongoing Phase I/II trial is expected to complete enrollment for the standalone Allocetra stage and the initial low-dose combination therapy stage, with another anti-PD1 immune checkpoint,  by the end of the second quarter. Once fully enrolled, the study’s primary goal is to measure the safety of Allocetra alone and as a combination therapy. But researchers will also track overall response rate, progression-free survival, overall survival and other measures of how effective the therapies were over a 12-month span following dosing. 

Allocetra And Tislelizumab Both Aim To Enhance The Immune System’s Ability To Fight Cancer

Allocetra is a novel immunotherapy that works by entering a patient’s own macrophages and reprogramming them to fight cancer. Macrophages are a type of white blood cell that act as a first line of defense for the immune system. They patrol the body for potential pathogens, dead cells and other unwanted toxins and microorganisms. When they find one, they engulf it and destroy it. 

While cancer cells should be high on their priority list of targets, the disease has evolved unique defense mechanisms to evade detection and trick macrophages into defending the cancer cells against other immune cells that try to target them. These manipulated macrophages interfere with the body’s own ability to fight cancer and can block some of the leading immunotherapies researchers have developed from working at their full potential.

Allocetra’s goal is to get inside those macrophages and reverse that manipulation, returning them to their homeostatic state so that they can recognize cancer cells for the threat that they pose and potentially clear the path for other immunotherapies to fight the disease without interference.  

In the current Phase 1/2a trial, the other immunotherapy is tislelizumab. Beigene’s drug candidate is an anti-PD-1 checkpoint inhibitor, which means it blocks that particular checkpoint on a cell which is used like an “off switch” to tell the immune system to leave that cell alone. Using this “off switch” is one of the key ways cancer evades detection by the patient’s immune system. By blocking it, tislelizumab is meant to remove cancer’s ability to hide from the immune system. 

In combination, the two immunotherapies would take away two of cancer’s best defense mechanisms and make the disease much more vulnerable to the patient’s own immune system, including the army of newly reprogrammed macrophages. 

Earlier preclinical trials that used a combination of Allocetra and an anti-PD1 immune checkpoint have already yielded promising results. In a study of ovarian cancer, conducted at the Yale Cancer Center, for example, mice that received the combination therapy saw an 83% increase in survival duration and significantly improved overall survival rates. 

Featured photo by Olga Kononenko via Unsplash

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