Drug developed in part by MUSC holds promise for treating advanced prostate cancer

January 06, 2021
Dr. Michael Lilly stands in the lobby of Hollings Cancer Center
Dr. Michael Lilly is leading a Phase II clinical trial that will hopefully result in additional treatment options for prostate cancer patients. Photo by Emma Vought

With a goal of improving survival for men with metastatic prostate cancer, researchers from MUSC Hollings Cancer Center are testing a new drug that may help to expand treatment options for patients whose disease is progressing despite treatment with standard therapies. The study will also examine patients’ genetic profiles for clues as to which men may be more responsive to the new therapy.

The investigational drug, called opaganib, is no stranger to Hollings researchers, as it was developed in part at the Medical University of South Carolina through the work of Charles Smith, Ph.D., and Besim Ogretmen, Ph.D. The first human trial was also conducted at MUSC, with the results showing that the drug was well-tolerated and provided some clinical benefit.

Opaganib works by selectively targeting an enzyme that regulates the balance between two types of lipids in the body: one that is more likely to help the cancer to grow and spread, and one that is more likely to cause the cancer cells to die. As far as the researchers know, the drug is the only one in development that can shift this balance to create more of the lipids that help to kill the cancer cells.

Because of the way it works, opaganib may provide benefit in multiple cancer types and has already been tested in both gallbladder cancer and multiple myeloma. The drug is also currently being tested as a potential treatment for patients with severe COVID-19-related pneumonia.

In this Phase II trial led by Hollings oncologist Michael Lilly, M.D., men with prostate cancer that has spread to other parts of the body will be enrolled once they have begun to lose benefit from standard treatment with hormone-blocking drugs, which are used to lower the body’s testosterone level and starve the cancer. When the cancer learns to “outsmart” these drugs and grow, despite low levels of testosterone, the hormone-blocking drugs become ineffective, and patients are typically placed on chemotherapy.

“While chemotherapy has benefits, it also has side effects, and most people would rather have a treatment like opaganib that is taken orally than something that requires frequent IV infusions,” said Lilly. “We believe there’s a need for developing additional oral agents, particularly ones that don’t act as hormone-blocking agents.”

Developing new classes of drugs to treat metastatic prostate cancer is critical, said Lilly, because hormone-depleting drugs and chemotherapy are currently the only treatment options for these patients. While both treatments typically provide some benefit to patients, both eventually stop working, often within a few months.

“We hope this study will make a difference by giving patients additional treatments that will reduce the growth of their cancer and thus improve how well and how long they live. It’s an exciting field to be able to work in — to develop something new that will hopefully benefit patients.”
— Dr. Michael Lilly

“There’s a limited amount of new territory you can explore with those agents. There are only so many ways you can reduce testosterone, and while we have dozens of chemo drugs, the majority have little or no activity in prostate cancer,” said Lilly. “We need some fundamentally new drugs that have different targets, different properties and different side effect profiles. We’re delighted to see patients respond to chemotherapy and hormone-blocking drugs, but we need treatments that will work for years.”

The trial will enroll roughly 60 men across multiple sites, including Hollings and Emory University. Participants in the trial will receive opaganib orally twice per day, in addition to continuing the standard hormone-blocking drugs, to determine whether adding this investigational drug into the mix can slow or halt the cancer’s progression. Participants will remain on the drug for a minimum of four months, assuming there are no adverse events, and they can remain on the treatment for as long as there is some benefit and tolerable side effects.

If the drug shows some efficacy in treating prostate cancer, researchers plan to explore other combinations, such as using opaganib earlier in a patient’s treatment or using higher doses.

While the trial is still in its early stages, Lilly is thrilled that the trial’s first patient, who was enrolled more than seven months ago, is doing well and has seen some obvious benefit.

“We hope this study will make a difference by giving patients additional treatments that will reduce the growth of their cancer and thus improve how well and how long they live,” said Lilly. “It’s an exciting field to be able to work in — to develop something new that will hopefully benefit patients.”

The study will also examine the genetic profiles of patients who are enrolled to see if there are any markers that potentially could identify patients who would respond well to the drug. They hypothesize that patients who have a particular genetic mutation may be most sensitive to the drug, but more information is needed to know for sure.

Aside from the benefits the trial could bring to patients with advanced prostate cancer, Lilly is proud to lead this investigator-initiated study as an example of Hollings’ commitment to bringing new discoveries to the bedside.

“A critical mission for the cancer center is bringing in the newest, most innovative types of treatments and making them available to our community,” said Lilly. “This early-phase, novel work is oriented toward identifying a whole new way of treating cancers.”

Anyone interested in learning more about this trial or wishing to participate can contact hcc-clinical-trials@musc.edu.

This research is supported by the National Cancer Institute (grant CA203628).