The newest cancer treatment on the market owes something to one of the earliest advocates for modern science. In his work Novum Organum, which is widely credited with introducing the scientific method, Francis Bacon wrote of the need for creative thinking to achieve anything new, saying that it would be a mistake, “to expect that things which have never yet been done can be done except by means which have never yet been tried.” There’s a lesson in that quote when it comes to applying the scientific method to the search for new cancer treatments. By following it, researchers in the Abramson Cancer Center of the University of Pennsylvania (ACC) just helped bring new hope to patients with multiple myeloma who are out of all other options.

Earlier this month, the U.S Food and Drug Administration (FDA) granted accelerated approval to a drug called selinexor (Xpovio). It’s a cancer drug that’s unlike anything else oncologists have ever tried before. It’s not an immunotherapy, and it doesn’t target any specific mutation in a tumor. Instead, it’s a pill known as a selective inhibitor of nuclear export, and it targets the systems that cells have to keep some molecules in the nucleus – the command center of the cell – and others out. Cancer cells, in particular, need to export tumor suppressing proteins from the nucleus so the tumor itself can grow and survive. Selinexor works by blocking the protein that shuttles the tumor suppressants out of the nucleus; a protein known as XPO1.

“The medication actually goes into the nucleus of the cell and affects where proteins are located, which is not something we’ve ever targeted before,” said Dan Vogl, MD, MSCE, an associate professor of Hematology-Oncology in the Perelman School of Medicine and a member of the ACC. Vogl led the first part of the Phase II trial on selinexor – published in the Journal of Clinical Oncology in 2018 – and advocated to the FDA for its approval after completion of the second part of that trial.

The trial showed that 25 percent of multiple myeloma patients respond to treatment with a combination of selinexor and the steroid medication dexamethasone, in a population of patients who had already received and were no longer benefitting from all of the other highly effective myeloma medications available. That data led the FDA to conditionally approve the drug for multiple myeloma patients who have undergone four or more prior therapies for their disease. Still, the approach is not without risk. The drug also targets the nuclei of healthy cells, meaning patients can experience serious and potentially deadly side effects.

“The concerns about side effects are real. It’s not an easy drug to take as a patient or to give is a physician,” Vogl said. “But this approval is properly placed. This is a drug we can give patients later in treatment when all other options have failed.”

Vogl cited two such patients, one of whom testified to an FDA committee about how important this drug was for its ability to extend her life and even increase her quality of life. Another patient, Vogl said, had as little as a week to live, took the drug and lived for another year and a half, surviving long enough to see her granddaughter get engaged.

“We are a cancer center that fights for all patients,” said ACC Director Robert Vonderheide, MD, DPhil. “This accelerated FDA approval shows that the science we pursue provides hope for patients who might otherwise have no other treatment options.”

Vogl echoed that sentiment, saying that while outcomes have improved in multiple myeloma overall, there are still too many patients who develop disease that is resistant to all available therapies. When that happens – whether it means a fourth line therapy, fifth, sixth, or beyond – patients need a new treatment option with a different mechanism of action to beat cancer’s resistance.

“Because this drug has that new mechanism of action, its effectiveness does not depend on what previous treatments a patient may have gotten, how aggressive the cancer is, or how high risk the cancer is based on genetic profiling: this drug led to responses across the board,” Vogl said.

This is the latest approval tied to research at the ACC, from the groundbreaking approval of CAR T therapy in August 2017, to AZEDRA for rare neuroendocrine tumors in July 2018, to XOSPATA for acute myeloid leukemia with a FLT3 mutation in November 2018. Despite the conditional FDA approval for selinexor, the drug’s long term fate could be decided by several ongoing studies. One of those is a Phase 3 trial looking at a lower dose of the drug combined with another standard myeloma therapy. Other studies are investigating selinexor in lymphoma, leukemia, and sarcoma – the last of which is ongoing at Penn.

In the meantime, it’s now an option doctors can offer to their sickest myeloma patients, a reality that exists because of the work of scientists who realized that to achieve something that’s never been done, you need to think of something no one else has tried.

Editor’s Note: Vogl has served as a scientific consultant for Karyopharm and has received honoraria for his work.