The Alexandrov National Cancer Centre in Belarus has initiated a Phase 2 clinical trial to test a new DNA vaccine, Elenagen, in patients with inoperable, late-stage cancers affecting the breast, ovaries, stomach, or prostate.
Patients in the trial will receive either standard chemotherapy plus Elenagen, or standard chemotherapy alone. The analysis will compare these two approaches for the time it takes for the cancer to progress, overall survival, and tumor regression.
Elenagen, developed by Boston, Massachusetts-based CureLab Oncology, which also provided the product to colleagues in Belarus, is a DNA vaccine made of a circular piece of DNA (plasmid) that when injected, triggers the production of the encoded protein in cancer cells, stimulating the immune system to attack those cells as a foreign invader.
The protein encoded by Elenagen is ubiquitin-binding protein p62, alternatively called sequestosome-1 (p62/SQSTM1). This protein, which is elevated and required for growth and metastases in almost all human tumors, usually is involved in the cellular process of eliminating unnecessary and abnormal products from cells. That process is known as autophagy.
Elenagen is meant to induce an immune response against this protein, eventually leading to cancer cell death. Importantly, p62 is dispensable for healthy cells, which reduces the risk of toxicity.
“We assessed hundreds of potential products according to the following criteria: high safety as demonstrated in phase I/IIa clinical trial, encouraging first signs of synergistic effects with chemo-, radio- and immunotherapies, the economic feasibility of the future product and its accessibility for the healthcare system, and scientific novelty. Elenagen satisfied all of these criteria,” Oleg Sukonko MD, PhD, said in a press release. Sukonko is head of the Alexandrov National Cancer Centre.
The Phase 1/2b clinical trial supporting Elenagen treatment enrolled 27 patients with advanced solid tumors, including breast, colon, kidney, lung, and ovarian cancers, and the skin cancer melanoma.
The trial, conducted at four clinical sites in Russia, first treated a group of 15 patients with increasing doses of Elenagen (from 1 to 5 mg weekly doses) to determine an optimal dose. After showing no dose-response effect, which is common for DNA vaccines, an additional 12 patients received the lowest, 1 mg dose. Patients whose cancer had progressed after Elenagen then were treated with standard chemotherapy.
Overall, 12 patients achieved stable disease for at least eight weeks. Four of those patients showed more durable tumor control, increasing from 24 to 32 weeks. Interestingly, patients who had failed to respond to several prior rounds of chemotherapy, were now responsive to that same chemotherapy regimen after receiving Elenagen, suggesting the vaccine was able to restore tumor sensitivity to chemotherapy.
The trial reported only mild adverse side effects, with the most common being rash or swelling at the injection site, nausea, fatigue, and fever, all resolved without the need for additional treatment. No patient discontinued treatment.
According to CureLab’s website, clinical trials in the U.S. are expected to begin this year.
“Although in the coming year we are planning to start phase II clinical trials of Elenagen in breast and ovarian cancers in the US and multiple other countries, it was very important for us to begin with Belarus, the country which was the most hit by Chernobyl,” said Alex Shneider, PhD, founder and CEO of CureLab Oncology. Shneider was referring to the disastrous 1986 nuclear power plant accident in Ukraine.