For more than 20 years, Dr. Laura Soucek, from the Vall d'Hebron Institute of Oncology (VHIO), has been working to inhibit the Myc gene, key in the development and maintenance of most tumors. Despite the widespread belief that it was untreatable, due to issues such as its location in the nucleus of cancer cells, Soucek persisted in research that is increasingly closer to reaching the market. The method the doctor found to inhibit this oncogene was through Omomyc, a therapeutic mini-protein that prevents Myc from binding to DNA. In cancer patients, when Myc manages to bind to DNA, it causes diseased cells to multiply uncontrollably. With Omomyc, Myc is unable to promote tumor growth.
After demonstrating in the preclinical phase that the protein developed at VHIO was capable of entering cells and reaching their nucleus, where the Myc oncoprotein is found, as well as stopping it, a clinical trial began in April 2021 at the Vall d'Hebron hospitals in Barcelona, San Chinarro and the Giménez Díaz Foundation, the latter two in Madrid. In the trial, 22 patients participated who were administered the drug intravenously once a week to check its safety and see if there were signs of cancer control. Participants had various solid tumors ---located in organs and not in the blood--- with metastases, including sarcomas, pancreatic, colon, and lung cancers, and had received at least three previous treatments, exhausting all possible therapeutic solutions.
Omomyc has successfully completed the phase I clinical trial and is ready to move on to a phase II trial, becoming the first Myc inhibitor to achieve this. "This drug is the first mini-protein targeting Myc to be tested in a phase I trial and demonstrates that it is capable of inhibiting the function of this oncogene in a safe and effective way," says Dr. Elena Garralda, director of the Cancer Molecular Therapy Research Unit (UITM) – CaixaResearch at VHIO.
According to the results of the trial, which could only be evaluated in 12 patients, eight patients ---more than half--- showed stable disease in which tumor growth had stopped after nine weeks of treatment. "It is still too early to evaluate the drug's activity, but we are seeing disease stabilization in some patients," adds the doctor.
Garralda highlights the case of a patient with pancreatic cancer, one of the most difficult, who remained in the study for more than six months, and in whom the tumor was reduced by 8% and there was an 83% reduction in tumor-derived DNA circulating in the bloodstream. There is also a patient with a salivary gland tumor whose disease remains stable and is still in the study after 16 months, and a patient with sarcoma, who had responded very little to previous treatments, who remained stable for 8 months.
The study to test Omomyc also had to evaluate the possible side effects of the new drug. The most common adverse effects were mild reactions to the intravenous infusion, such as chills, fever, nausea, rashes, and low blood pressure. As higher doses were tested, more reactions occurred, but they could be easily treated. "The most exciting thing is that biological markers clearly show that we are successfully inhibiting Myc. In addition, the adverse side effects are mostly mild, which is important when we start thinking about the next steps and combining Omomyc with chemotherapy or other therapies," explains Dr. Garralda.
Another important aspect has focused on evaluating the drug's life in the patient's body and seeing if it was sufficient to have an impact on the tumor. It has been concluded that Omomyc remained for at least 50 hours in the blood, and possibly even longer in the tumors.
The combination of Omomyc with existing treatments will serve to evaluate its efficacy in phase II, after obtaining very promising preliminary results in phase I. According to Dr. Laura Soucek, they are in talks with pharmaceutical companies to develop a new trial. They expect it to start between spring and summer of next year.