Researchers at IU School of Medicine have developed a promising combination drug therapy for triple negative breast cancer that was shown to be safe and well-tolerated in early-stage studies. Milan Radovich, PhD, and his colleagues tested a combination of two drugs — gedatolisib (an experimental small molecule) and cofetuzumab pelidotin (an experimental biologic) — as part of an initial safety study for triple negative breast cancer patients. Triple negative breast cancer is one of the most aggressive forms of the disease, with fewer approved treatment options than any other type of breast cancer.

This study, based on years of research, was inspired in part by a popular arcade game, "Whac-A-Mole." In the game, even if a player can accurately hit a disease target (the mole), another one often pops up in a different spot. Preclinical work in Radovich’s laboratory, led by PhD student and laboratory director Jeffrey Solzak, MS, MBA, found this to happen when treating triple negative breast cancers too. They would focus treatment on a specific genomic abnormality commonly seen in triple-negative breast cancer, only to have the cancer rapidly compensate by activating another pro-cancer target. When both were hit, they observed significant anti-cancer synergy. These preclinical results were published by Solzak et al. in Nature Partner Journals Breast Cancer. By performing this clinical trial, Radovich and his colleagues sought to translate these laboratory findings to patients.  

Radovich, who is an associate professor of surgery at IU School of Medicine, says they were pleased with the results. The study team led by Radovich and Kathy Miller, MD, Ballvé Lantero Professor of Oncology at IU School of Medicine, enrolled 18 patients, who received the drug combination. Importantly, the trial first found that the combination was safe. Further, the trial found that about a third of patients had either tumor shrinkage or stable disease for 18 weeks or greater. One patient reported tumor shrinkage by 52 percent after six weeks of treatment. The team was happy to see an early signal of this drug combination having clinical activity in this very hard-to-treat disease.

“Our goal has always been that anything we do in the lab has to have an end-point that focuses on the patient, where the patient will benefit,” said Radovich, who also co-leads the IU Precision Health Initiative triple negative breast cancer disease research team. "We were able to start with an idea and work through the experiments to take this to a clinical trial. At IU, I feel like we do an exceptional job of crossing the divide between basic science and clinical research, and this is just another example of that."

Radovich presented the findings during a virtual poster session at the San Antonio Breast Cancer Symposium (SABCS) in December 2020. SABCS is the most influential gathering of breast cancer researchers and physicians in the world. Radovich also gave a plenary presentation about triple negative breast cancer research during the symposium in 2019.

This drug combination was developed through early work of analyzing triple negative breast cancer tumors and comparing them with healthy, non-cancerous breast tissue from the Komen Tissue Bank at IU Simon Comprehensive Cancer Center, the world’s only healthy breast tissue bank. Miller was the co-primary investigator of this study with Radovich. In addition to Radovich, Solzak, and Miller, other investigators from the Indiana University Melvin and Bren Simon Comprehensive Cancer Center included, Sunil Badve, MD; Anna Maria V. Storniolo, MD; Tarah J. Ballinger, MD, and Bryan P. Schneider, MD. Chao Wang, MS; Bradley A. Hancock, BS, MT; and Sandra K. Althouse, PhD are contributing researchers at IU School of Medicine.

Radovich and his colleagues are now working on the next stage of research, which will be a phase II study. This phase will build on these findings, involving even more triple negative breast cancer patients.

This study was supported by the IU Grand Challenge Precision Health Initiative, Breast Cancer Research Foundation, Vera Bradley Foundation for Breast Cancer, 100 Voices of Hope, The Catherine Peachey Fund and Pfizer.