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FDA Grants Accelerated Approval to Bristol Myers Squibb’s Augtyro for the Treatment of NTRK-Positive Locally Advanced or Metastatic Solid Tumors

Image Credit: Adobe Stock Images/Oksana Smyshliaeva

The FDA has granted accelerated approval to Bristol Myers Squibb’s (BMS) Augtyro (repotrectinib), a tyrosine kinase inhibitor (TKI), for treating adult and pediatric patients over 12 years of age with neurotrophic tyrosine receptor kinase (NTRK)-positive locally advanced or metastatic solid tumors. According to the company, the approval of Augtyro was based on encouraging data from the Phase I/II TRIDENT-1 trial, which showed meaningful response rates in both TKI-naïve and TKI-pretreated patients.1

“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, chief of the Early Drug Development Service, Memorial Sloan Kettering Cancer Center, in a press release “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.”

Previously approved indications for Augtyro include for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer, and adult and pediatric patients over 12 years of age with solid tumors that have a NTRK gene fusion, locally advanced or metastatic, or where surgical resection is likely to result in severe morbidity, and tumors that have progressed following treatment or that have no satisfactory alternative therapy.

TRIDENT-1 is a global, multicenter, single-arm, open-label, multi-cohort clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of Augtyro in 426 patients with locally advanced or metastatic NTRK gene fusion-positive (NTRK1/2/3) solid. Results were also able to determine the dosage level for the Phase II trial.

TKI-naïve patients exhibited a confirmed objective response rate (cORR) of 58%, with 43% partial responses (PR) and 15% complete responses (CR). After a year of treatment, 83% of patients were still responding to therapy. This included a median follow up of 17.8 months, although the median duration of response (mDOR) has not yet been reached. With a median follow up of 20.1 months in TKI-pretreated patients, there was a cORR of 50%, all PRs, with 42% maintaining response after a year, and a mDOR of 9.9 months.

Treatment with Augtyro was disrupted due to adverse events (AEs) in 50% of trial participants, with serious AEs reported in 35% of participants. Serious AEs included pneumonia, pneumonia aspiration, cardiac arrest, sudden cardiac death, cardiac failure, hypoxia, dyspnea, respiratory failure, tremor, and disseminated intravascular coagulation. The most common AEs were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.

As Phase II begins, the primary endpoint of the trial will be objective response rate (ORR) as evaluated by BICR. Secondary endpoints include DOR according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by BICR, and intracranial response in patients with measurable brain metastases.1

“Today’s 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, SVP, medical oncology, Bristol Myers Squibb, in the press release. “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.”


U.S. Food and Drug Administration Approves Augtyro™ (repotrectinib), a Next-Generation Tyrosine Kinase Inhibitor (TKI), for the Treatment of Patients with NTRK-Positive Locally Advanced or Metastatic Solid Tumors. BMS. June 13, 2024. Accessed June 14, 2024.