Phase I Trial Shows Experimental Mini-Protein May Be Able to Inhibit the Cancer-Driving MYC Gene

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Researchers have found that a new drug may be able to target—and for the first time, inhibit—the function of the MYC gene. Until now, no other drug has been able to do this safely and effectively, according to findings from a phase I clinical trial published by Garralda et al in the European Journal of Cancer.

MYC is one of the ‘most wanted’ targets in cancer because it plays a key role in driving and maintaining many common human cancers, such as breast, prostate, lung, and ovarian cancer[s]. To date, no drug that inhibits MYC has been approved for clinical use,” first study author Elena Garralda, MD, Director of the Early Drug Development Unit at the Vall d’Hebron Institute of Oncology, said of the new research, which was also presented at the 34th European Organisation for Research and Treatment of Cancer (EORTC)–National Cancer Institute (NCI)–American Association for Cancer Research (AACR) Symposium on Molecular Targets and Cancer Therapeutics (Abstract 7).

Research Background

The researchers developed a mini-protein called OMO-103 that can enter cells and reach the nucleus. In experiments in the lab and in mice, they had shown that the protein may have successfully inhibited the ability of MYC to promote tumor growth by blocking the gene’s ability to control the flow of information from many common genetic mutations found in cancer.

After this preliminary research, Dr. Garralda and her colleagues enrolled 22 patients in a phase I clinical trial to assess the safety of OMO-103 and to validate its ability to control cancer. The patients had a range of solid tumors, including pancreatic, colon, and non–small cell lung cancers (NSCLC). They had all been heavily pretreated, having received a range of 3 to 13 other treatments previously.

Study Methods and Results

OMO-103 was given intravenously once a week at six dose levels ranging from 0.48 to 9.72 mg/kg. The researchers took biopsies from the tumors at the start of the study and after 3 weeks of treatment to assess levels of MYC gene activity and other biological indicators for cancer.

After 9 weeks, computed tomography (CT) scans showed stable disease and halted cancer growth in 8 out of 12 patients. Of these, two had pancreatic cancer, three had colon cancer, one had NSCLC, one had sarcoma, and one had salivary gland cancer.

“It’s still very early … to assess [the effectiveness] of the drug, but we are seeing stabilization of disease in some patients. Remarkably, one patient with pancreatic cancer stayed on the study for over 6 months; his tumor shrank by [8%] and there was a reduction in tumor-derived DNA circulating in the bloodstream. The patient with a salivary gland tumor has stable disease and is still in the study after 15 months,” highlighted Dr. Garralda. “The most exciting thing is that biological markers show that we are targeting MYC successfully. In addition, the adverse side effects are mostly mild, which is important when we start to think about next steps and combining OMO-103 with chemotherapy or other therapies,” she continued.

The most common treatment-related adverse side effects were mild reactions to the intravenous infusion, such as chills, fever, nausea, rash, and low blood pressure. Higher dose levels were associated with more reactions to the infusion but were easily treated. Inflammation of the pancreas, which occurred in one patient, was the only dose-limiting reaction.

Analysis of how OMO-103 was absorbed and processed in the body indicated that it remained in the blood serum for at least 50 hours.

“We have experimental evidence that this could be a significant underestimat[ion] of how long the drug remains in the tumor. Evidence from our work in mice suggests drug concentrations in the tumor that are at least fourfold higher than in the blood. In addition, even after long-term treatment, we could not detect any antidrug antibodies, which can decrease the amount of [the] drug available and therefore make it less effective,” Dr. Garralda emphasized, concluding that, “OMO-103 is the first MYC inhibitor to successfully complete a phase I clinical trial and to be ready to proceed to a phase II trial. We have determined the recommended dose for phase II to be 6.48 mg/kg.”


MYC plays an important role in many cell-signaling pathways that promote a range of different cancers but has long been perceived as an ‘undruggable’ target. Researchers have spent much time and energy on the search for drugs that target MYC successfully, but it has proven hard to develop therapies that are effective but don’t have side effects that are too severe for patients to tolerate. These results showing that patients typically experienced mild adverse side effects to OMO-103 are important when considering next steps and how it might be combined with chemotherapy. We look forward to the results from the phase II trial with interest,” said James L. Gulley, MD, PhD, Co-Director of the Center for Immuno-Oncology and Director of the Medical Oncology Service at the Center for Cancer Research at the NCI, and Co-Chair of the 34th EORTC–NCI–AACR Symposium on Molecular Targets and Cancer Therapeutics, who was not involved in the study.

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