US - FDA Approves BMS’ Augtyro (repotrectinib) for ROS1+ Non-Small Cell Lung Cancer (NSCLC)

On Nov. 15, 2023, US FDA approved BMS’ Augtyro (repotrectinib) for locally advanced or metastatic non-small cell lung cancer (NSCLC) with ROS1 gene rearrangement(s) (ROS1+). This is the first FDA approval that includes ROS1+ NSCLC patients who have previously received a ROS1 tyrosine kinase inhibitor (TKI), in addition to patients who are TKI naïve.

Background: ROS1 gene fusions are rare and occur in about 1-2% of patients with NSCLC.

This application was granted Priority Review, Breakthrough Designation, and Fast Track Designation. Assessment Aid, a voluntary submission from the applicant, was used to facilitate FDA review.

TRIDENT-1 (NCT03093116) is a global, multicenter, single-arm, open-label, multi-cohort Phase 1/2 clinical trial in ROS1+ locally advanced or metastatic NSCLC.

Both ROS1 TKI-naïve and ROS1 TKI-pretreated patient subsets were included for efficacy evaluation:

·       71 ROS1 TKI-naïve patients who received up to 1 prior line of platinum-based chemotherapy and/or immunotherapy

·       56 patients who received 1 prior ROS1 TKI with no prior platinum-based chemotherapy or immunotherapy

The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR) according to RECIST v1.1 as assessed by blinded independent central review.

ORR in the ROS1 TKI-naïve group was 79% (95% CI: 68, 88) and 38% (95% CI: 25, 52) in the ROS1 TKI-pretreated group.

Median DOR was 34.1 months (95% CI: 25.6, not evaluable) in the ROS1 TKI-naïve group and 14.8 months (95% CI: 7.6, not evaluable) in the ROS1 TKI-pretreated group.

Responses were observed in intracranial lesions in patients with measurable central nervous system metastases, and in patients with resistance mutations following TKI therapy.

The most common (>20%) adverse reactions were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness.

Augtyro (repotrectinib) is expected to be available in the US in mid-December 2023. 

An FDA-approved test to detect ROS1 rearrangements for selecting patients for treatment with Augtyro (repotrectinib) is not currently available.

Link to FDA approval announcement

Link to BMS press release

Link to Augtyro prescribing information

Link to OncLive news