PRINCETON, NJ — Bristol Myers Squibb announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval of Augtyro™ (repotrectinib) for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy. The approval is based on results from the Phase 1/2 TRIDENT-1 study, which evaluated Augtyro in adult patients with NTRK-positive solid tumors. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

“NTRK fusion-positive tumors can present challenges in the clinical setting, which is why it is important that we have additional treatment options for these patients,” said Alexander Drilon, MD, TRIDENT-1 global trial lead and Chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center. “The FDA approval of repotrectinib adds an important tool to our toolbox, offering oncologists a next-generation TKI that can be used across a broad range of NTRK fusion-positive solid tumors for both TKI-naïve and TKI-pretreated patients.”

The TRIDENT-1 trial included both TKI-naïve (n=40) and TKI-pretreated (n=48) patients with NTRK-positive locally advanced/metastatic solid tumors collectively representing 15 different types of cancer. In TKI-naïve patients, with a median follow up of 17.8 months, 58% (95% CI: 41 to 73) had a confirmed objective response rate (cORR); of those, 43% experienced partial responses (PR) and 15% had complete responses (CR). Of the TKI-naïve responding patients, 83% were still in response at one year with Augtyro. The median duration of response (mDOR) was not yet reached. In TKI-pretreated patients, with a median follow up of 20.1 months, the cORR was 50% (95% CI: 35 to 65); of those, 50% experienced PR and no patients achieved CR. Additionally, 42% of TKI-pretreated responding patients were still in response at one year with Augtyro. The mDOR was 9.9 months (95% CI: 7.4 to 13.0). Among those who had measurable central nervous system (CNS) metastases at baseline, intracranial response was observed in 2 out of 2 TKI-naïve patients and in 3 out of 3 TKI-pretreated patients.

Augtyro is associated with the following Warnings & Precautions: central nervous system (CNS) effects, interstitial lung disease (ILD)/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, skeletal fractures, and embryo-fetal toxicity.

“FDA approval of Augtyro for patients with NTRK-positive tumors adds to its indication in ROS1-positive NSCLC, showing its clinical value for more people across multiple genetic markers,” said Nick Botwood, senior vice president of Medical Oncology at Bristol Myers Squibb. “Previously, there was not an FDA approved treatment option for NTRK-positive cancers that was studied in both TKI-naïve and TKI-pretreated patients across solid tumors. This milestone helps address this area of unmet need and builds on Bristol Myers Squibb’s longstanding legacy of bringing innovations to individuals who are facing cancer and urgently seeking new treatment options.”

“Cancer can be frightening regardless of the type, but having a rare gene fusion driving it can be especially stressful and isolating,” said Susan Spinosa, president and patient co-founder of NTRKers, a patient advocacy group. “It’s exciting to know that there’s a new targeted therapy option for patients with NTRK-positive gene fusions, as this may offer hope to patients and their loved ones navigating this difficult journey.”

Based on clinical and pharmacokinetic data, the recommended dose for Augtyro for pediatric patients aged 12 years and older is the same as for adults, 160 mg orally once daily for 14 days followed by 160 mg twice daily until disease progression or unacceptable toxicity. The safety and effectiveness of Augtyro have not been established in pediatric patients younger than 12 years of age with solid tumors who have an NTRK gene fusion. This is the second indication for Augtyro in the U.S., following its full approval for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC in November 2023.

Disclosure: Dr. Drilon has provided advisory and speaking services to Bristol Myers Squibb.