Augtyro Approved in NTRK-Positive Cancers, Pediatric Research Continues

With its June approval of Augtyro (repotrectinib) for patients with solid tumors harboring an NTRK gene fusion, the agency has made another treatment option available for adult and some pediatric patients alike.

The approval was for patients 12 years old and older with locally advanced disease, meaning it has grown beyond its initial location but not to other body parts, or metastatic (the cancer spread elsewhere in the body). In this patient population, resection (surgical removal) would be likely to result in severe morbidity or health complications. Patients must have received prior treatments and have no other satisfactory therapies available to them.

The application for the approval was supported by findings from two clinical trials, the phase 1/2 TRIDENT-1 study of adult patients and the phase 1/2 CARE study of pediatric patients, according to a news release from manufacturer Bristol Myers Squibb.

CURE® spoke with one of the investigators of CARE, Dr. Theodore Laetsch, a pediatric oncologist who leads the Development Therapeutics Program and Very Rare Malignant Tumors Program at the Children’s Hospital of Philadelphia, about Augtyro and what unmet questions remain for this pediatric patient population as research continues.

CARE, Laetsch noted, is still recruiting patients and researchers hope to share data from the trial in the near future.

CURE®: What is the basic science behind how Augtyro works?

Laetsch: This drug blocks specific signaling pathways that can be turned on abnormally in some cancers. These signaling pathways are turned on when two genes that are not supposed to be attached in a cancer cell stick together in what we call a gene fusion, and that drives those cells to become cancer. [Augytro] blocks the signaling from these fusion proteins, and therefore turns off the program that's turning those cells into cancer. This causes the cancer cells to die or to stop growing for a long period of time.

It works very differently than traditional chemotherapy which tries to kill cells by damaging DNA. This is a much more targeted therapy that blocks a specific genetic change that we see in an individual patient’s cancer cells — it’s a precision medicine.

How common is it that an approval comes through citing findings of two different studies, approving a drug for both the adult and pediatric population as well?

The FDA has really focused on ensuring children are included in drug development for the last several years. Two prior drugs in this class of drugs called TRK inhibitors, [Vitrakvi (larotrectinib)] and [Rozlytrek (entrectinib)], were approved previously. Both of those approvals include children, and both approvals were based on evaluating data across multiple studies that included adult and pediatric patients.

There has been a lot of advocacy that has resulted in legislation that encourages and in many cases requires earlier clinical trials of new drugs in children. I think we're starting to see some of the results of that work through approvals like this. It has been much more common recently to see approvals of new drugs that specifically include patients 12 and older.

For this patient population of pediatric patients 12 and older, what was the prior standard of care in this patient population before this approval?

I mentioned, there are two other FDA-approved TRK inhibitors, both of which are now approved for pediatric and adult patients. This class of drugs has become the standard of care for TRK-fusion-driven cancers.

What's unique about [Augtyro] is that it can block some of the ways cancer cells become resistant to those other medications. Prior to this approval, there weren’t good standard of care options for patients whose cancers progress on a different TRK inhibitor.

What are some potential unmet needs that still remain for this patient population?

There are a lot of questions that still remain about how best to use TRK inhibitors including [Augtyro]. Some of these are being studied in ongoing clinical trials: Can we replace chemotherapy with these drugs? How do we integrate them with other treatments? For example, for patients with thyroid cancer, should we combine these drugs with radioiodine, which is the current standard of care?

And then, of course, it's especially important to understand the long-term side effects of these medications in children. These medications are very effective and we hope many of our patients will have a very long life following treatment.

Transcription has been edited for clarity and conciseness.

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