FDA Approves FoundationOne CDx Diagnostic for Tovorafenib in Brain Tumors

The approval marks Foundation Medicine’s first companion diagnostic indication to exclusively support pediatric patients with brain tumors.

The FDA has approved FoundationOne CDx for use as a companion diagnostic for tovorafenib (Ojemda), a type II RAF inhibitor, to treat patients 6 months of age or older with relapsed/refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation, according to a press release from the diagnostic’s developer, Foundation Medicine, Inc.¹

Supporting data for the approval in this indication came from the phase 2 FIREFLY-1 trial (NCT04775485) published in Nature Medicine, in which tovorafenib elicited an overall response rate (ORR) of 67% (95% CI, 54%-78%) among 76 patients with BRAF-altered, relapsed or refractory pLGG, including 17% attaining a complete response and 49% attaining a partial response.² Furthermore, the clinical benefit rate (CBR) was 93%, with 26% of patients achieving a best overall response of stable disease. For patients with tumors harboring BRAF fusions the ORR was 69% (95% CI, 56%-81%) vs 50% (95% CI, 19%-81%) in those harboring BRAF V600E mutations.

In arm 1 of the trial, patients were given 420 to 600 mg^-2 oral tovorafenib once weekly, on days 1, 8, 15, and 22 of 28-day cycles. Treatment cycles were repeated until disease progression, unacceptable toxicity, drug holiday decision, or patient withdrawal. The primary trial end point was ORR, and secondary end points for arm 1 were CBR, PFS, DOR and TTR.

“Foundation Medicine is proud to partner with Day One to help healthcare providers connect pediatric patients and families with this treatment option,” Mia Levy, MD, PhD, chief medical officer at Foundation Medicine, said in the news release.¹ “Our high-quality tissue-based companion diagnostic test is uniquely capable of detecting both BRAF V600 mutations and fusions which enables providers to gain the complete genomic picture of their patient’s tumor and guide treatment decision making.”

The FDA previously granted accelerated approval to tovorafenib as a treatment for patients 6 months or older with relapsed/refractory pediatric low-grade glioma harboring a BRAF fusion or rearrangement in April 2024.³

Over 2200 pediatric central nervous system (CNS) tumors have been sequenced by Foundation Medicine, according to the press release, and is the only company to offer FDA-approved tissue and blood-based comprehensive genomic profiling tests. The FoundationOne CDx diagnostic test analyzes more than 300 cancer-related genes in a tumor tissue sample, which may determine whether tovorafenib is a suitable therapy for patients with BRAF-altered tumors.

“Historically, pediatric patients with pLGG have faced overwhelming [adverse] effects, both near- and long-term, from aggressive treatments like chemotherapy and radiation,” David Arons, president and chief executive officer at the National Brain Tumor Society, said in the press release.¹ “We are thrilled to see that there are now additional treatment options available for these children, as well as an FDA-approved companion diagnostic test to help identify more patients who may benefit from Day One’s therapy.”

The FoundationOne CDx diagnostic test is intended for prescription use only. It is intended to provide tumor mutation profiling for use by qualified health care professionals based on oncology guidelines for patients with solid malignant neoplasms. Furthermore, developers advise that test use does not guarantee a patient will be matched to treatment and that a negative test does not preclude that an alteration may be present. Additionally, patients may require a biopsy following the use with the assay.

References

1. U.S. Food and Drug Administration approves FoundationOne®CDx as a companion diagnostic for OJEMDA™ (tovorafenib) to treat the most common form of childhood brain tumor in pediatric patients. News release. Foundation Medicine, Inc. January 17, 2025. Accessed January 20, 2025. https://tinyurl.com/55jrpzdz
2. Kilburn LB, Khuong-Quang DA, Hansford JR, et al. The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. Nat Med. 2024;30(1):207-217. doi:10.1038/s41591-023-02668-y
3. FDA grants accelerated approval to tovorafenib for patients with relapsed or refractory BRAF-altered pediatric low-grade glioma. US FDA. April 23, 2024. Accessed January 20, 2025. https://tinyurl.com/yef2r5sk