A Phase 1/2a clinical trial is seeking patients with metastatic solid tumors who are unfit for surgery to participate in a study of BioLineRx‘s immunotherapy AGI-134.
The trial (NCT03593226) is expected to enroll 70 patients in the United Kingdom and Israel who have received all available therapies for their disease. It will test AGI-134 alone and in combination with the immune checkpoint inhibitor Keytruda (pembrolizumab).
AGI-134 is a synthetic fatty molecule that takes advantage of the body’s defense mechanisms against bacteria to cause cancer cells to die.
Humans do not produce anti-alpha-Gal (αGal), but bacterias and other mammals do. So, our immune system produces high levels of anti-αGal antibodies to fight these bacteria. AGI-134 is a molecule that binds to cancer cells, and labels them with the αGal, triggering an immune response against these cells.
While AGI-134 is injected directly into the tumor site, the treatment also induces durable responses against metastasis (cancer cells that have spread to distant organs). This happens because immune cells become primed against the cancer’s own molecules.
In mice with melanoma, AGI-134 completely eliminated tumors in more than half of the animals. The effects were even more pronounced when the drug was given in combination with medicines that unleash the immune system, like Keytruda.
“Numerous pre-clinical studies to date have demonstrated that treatment with AGI-134 leads to regression of established primary tumors, prevents growth of untreated distal secondary tumors, and triggers a vaccine effect that may prevent the development of future metastases,” Philip Serlin, BioLineRx’s CEO, said in a press release. “We are pleased to enter the clinic with our second lead oncology project.”
The clinical trial will be conducted in two parts. First, patients will receive escalating doses of intratumoral (injected into the tumor) AGI-134, to determine its safety and tolerability.
In the second part, researchers will continue to assess AGI-134’s safety and tolerability in multiple solid tumor types. Two additional groups — including patients with metastatic colorectal cancer and head and neck squamous cell carcinoma — will examine the combination of AGI-134 with Keytruda.
The trial will be conducted in several clinical sites across Israel and the U.K., and may be expanded to the U.S and some countries in Europe in 2019. More information is available on the trial page.
“We are very excited to be launching a first-in-human clinical trial assessing AGI-134 for the treatment of solid tumors,” said Mark Middleton, MD, professor at the University of Oxford and principal investigator of the trial. “AGI-134 represents a new mechanistic class of cancer immunotherapies, with a unique and highly differentiated mode of action.”