Day One Biopharmaceuticals on Sunday announced that its targeted therapy, tovorafenib, shrank tumors by at least 50% in most children diagnosed with the most common type of pediatric brain cancer, setting the stage for the approval of a new treatment for a rare, chronic disease, Jason Mast writes for STAT+.

New therapy shrinks trial participants' tumors by at least 50%

On Sunday, Day One released new data that expand on trial results released last year from 22 patients who received the targeted therapy tovorafenib. Among the trial participants, which now includes 69 pediatric low-grade glioma patients, 64% had their tumors shrink to less than half their original size—and three of those patients' tumors disappeared entirely. 

Along with the 44 patients whose tumors shrank significantly, 19 patients had stable disease, with their tumors declining by less than 50% or not experiencing significant growth. 

According to a press release, the patients' responses to the drug lasted 8.4 months, on average, though that number could increase as the trial continues. When the trial data were collected on Sept. 28, 77% of patients were still taking the drug.

The company said the response rate could also change. Among the 41 patients whose tumors decreased in size but did not disappear, 10 were still waiting for follow-up, confirmatory scans.

Before joining the trial, most patients had already been on an average of three different therapies—and almost 60% took a targeted therapy that functions on the same genetic pathway as tovorafenib.

"I think that it truly is promising," said Ira Dunkel, a pediatric oncologist at Memorial Sloan Kettering and chair of the Pediatric Brain Tumor Consortium, who was not involved in the work. Still, Dunkel noted that it is "important we get more details."

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With low-grade glioma, which is a chronic condition, patients' tumors often spontaneously recess sometime in their 20s, making the goal of treatment to minimize long-term complications until then.

While there are currently no targeted drugs specifically approved to treat low-grade glioma patients, two targeted therapies are frequently administered to patients who progress after chemotherapy. According to Dunkel, the exact importance of the drug will depend on how it compares to those therapies and how well it works on patients who did not respond to them.

"These data hint at, but don't provide complete answers to, those questions. In a best-case scenario, the drug could provide a new treatment for patients who have exhausted every other door," Mast writes.

"The most remarkable thing about this study is that most of the patients had received numerous prior lines of therapy," said Craig Erker, a pediatric oncologist at Dalhousie University in Halifax, Nova Scotia, who is not associated with the trial. "And they still see a good overall response."

The trial results suggest that the drug could prevent children from having to receive radiation, which is typically seen as a last resort since it has the potential to cause cognitive damage and can sometimes accelerate tumors. 

"For those patients, the clinical options really are limited," said Day One CEO Jeremy Bender. 

However, Dunkel noted that Day One's press release does not specify how many trial patients exhausted other treatment options. While many patients had taken another targeted drug, their cancer did not have to fail to respond to other treatments for them join the trial. 

"Doctors, for example, will often have patients take a drug for a couple of years and then remove treatment if the tumor is at bay," Mast writes. "The glioma of some patients on the trial may have progressed after stopping an earlier targeted drug."

"It's possible that these patients were all in the worst-case scenario and responded, which would be a big feather in the cap of the drug," Dunkel said. "Or it's possible that many of these patients were not in quite as dire a situation."

According to a spokesperson for Day One, the company's assumption is that another targeted therapy had an impact on most patients' cancer only for a period of time or not at all.

Meanwhile, Bender and Erker noted the importance of the stable disease rates, which are often dismissed in adult cancer trials.

"There is real value to being able to keep a tumor in check and prevent some of the effects that tumor growth can have, whether that's motor effects, cognitive, visual," said Bender. "That is different than what you see in other oncology settings.

During the first half of 2023, Day One plans to submit the drug for U.S. approval. "An OK from the [FDA] would not only make a new treatment available for young patients, but also offer an important validation point for Day One's thesis about how to develop drugs for kids with cancer," Mast writes. (Mast, STAT+ [subscription required], 1/8)