Repotrectinib (Augtyro™) Receives FDA Approval for ROS1-Positive Non-Small Cell Lung Cancer

On November 16, 2023, Rendin Pharmaceuticals, in partnership with Pfizer Inc., announced that repotrectinib (Augtyro™) has received approval from the U.S. Food and Drug Administration (FDA) for the treatment of locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) in adult patients.

Approval Based on TRIDENT-1 Study:
The approval was based on data from the open-label Phase 1/2 TRIDENT-1 study, which evaluated repotrectinib in patients who were either treatment-naïve or had received prior tyrosine kinase inhibitor (TKI) therapy. In treatment-naïve patients (n=71), the objective response rate (ORR) was 79%, the progression-free survival (PFS) was 35.7 months, and the median duration of response (mDOR) was 34.1 months. In patients previously treated with one ROS1 TKI and no chemotherapy (n=56), the ORR was 38%, and the mDOR was 14.8 months. Among patients with measurable brain metastases at baseline, 7 out of 8 TKI-naïve patients and 5 out of 12 patients who had received TKI therapy demonstrated intracranial responses.

Significance of Repotrectinib:
Dr. Jessica J. Lin, the principal investigator of the TRIDENT-1 study, thoracic oncologist at Massachusetts General Hospital, Assistant Professor of Medicine at Harvard Medical School, and M.D., commented:

"ROS1 fusion-positive NSCLC patients still need new treatment options to support critical treatment goals, including achieving durable responses."

"Based on the data we have seen in the TRIDENT-1 study, repotrectinib has the potential to become a new standard treatment choice for patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer."

Regulatory Status in China:
In June 2023, the National Medical Products Administration (NMPA) of China accepted the new drug application for repotrectinib for the treatment of locally advanced or metastatic ROS1-positive NSCLC in adult patients. In May 2023, repotrectinib was granted priority review by the NMPA. Currently, repotrectinib has received four breakthrough therapy designations in China.

Note: The mentioned drug and its indications are not yet approved or available in China.

Non-Small Cell Lung Cancer in China:
Lung cancer is the most common cancer type and a leading cause of cancer-related deaths in China. In 2022, there were approximately 871,000 new cases and 767,000 deaths from lung cancer in China. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases, with about 70% of NSCLC cases diagnosed as locally advanced or metastatic at initial presentation. In China, ROS1 rearrangements occur in approximately 2%-3% of advanced NSCLC patients.

The FDA approval of repotrectinib (Augtyro™) for ROS1-positive locally advanced or metastatic NSCLC represents a significant advancement in the treatment options available for this patient population. The promising results from the TRIDENT-1 study and ongoing regulatory processes in China highlight the potential of repotrectinib as a new standard of care for ROS1-positive NSCLC patients. Continued research and development efforts in targeted therapies offer hope for improved outcomes in lung cancer patients.