FDA Approves Repotrectinib for Non-Small Cell Lung Cancer

The U.S. Food and Drug Administration (FDA) has approved Bristol Myers Squibb’s repotrectinib (Augtryo) for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer. Repotrectinib is an orally administered tyrosine kinase inhibitor (TKI) that targets ROS1 oncogenic fusions. 

Approval is based on findings from the TRIDENT-1 study, a global, multi-center, single-arm, open-label, multi-cohort Phase I/II clinical trial that evaluated the safety, tolerability, pharmacokinetics and anti-tumor activity of repotrectinib in patients with advanced solid tumors. The primary end point of the study was objective response rate (ORR), or the proportion of patients treated within a certain time frame who experienced either a partial response (tumor size decreased) or complete response (no longer had signs of cancer). The study demonstrated an ORR of 79 percent. The median duration of response (mDOR) was 34.1 months. Additionally, among patients who had been pretreated with one prior ROS1 TKI and no prior chemotherapy (n=56), the ORR was 38 percent, and the mDOR was 14.8 months. Furthermore, among patients who had measurable central nervous system metastases at baseline, responses in intracranial lesions were seen in seven of eight TKI-naïve patients (n=71) and in five of 12 patients who were pretreated with TKIs (n=56). 

The most common adverse reactions that occurred in at least 20 percent of patients were dizziness (63 percent), dysgeusia (48 percent), peripheral neuropathy (47 percent), constipation (36 percent), dyspnea (30 percent), ataxia (28 percent), fatigue (24 percent), cognitive disorders (23 percent) and muscular weakness (21 percent). Permanent discontinuation of repotrectinib occurred in eight percent of patients in the study, with serious adverse events occurring in 33 percent of patients. Serious adverse events occurring in at least two percent of patients included pneumonia (5.7 percent), dyspnea (3.8 percent), pleural effusion (3.4 percent) and hypoxia (3 percent). Furthermore, fatal adverse reactions occurred in 4.2 percent of patients, including death, pneumonia, pneumonia aspiration, cardiac arrest, sudden cardiac death, cardiac failure, sudden death, hypoxia, dyspnea, respiratory failure, tremor and disseminated intravascular coagulation.