Taletrectinib can produce durable responses in patients with ROS1-positive non-small cell lung cancer (NSCLC), a phase 2 trial suggests.

Researchers found that taletrectinib produced responses in patients who were naïve to tyrosine kinase inhibitors (TKIs), those who had received prior treatment with crizotinib, and those who had brain metastases. 

These results were presented at the European Lung Cancer Congress 2023 by Dr Wei Li of Shanghai Pulmonary Hospital and Thoracic Cancer Institute at Tongji University School of Medicine in China. 

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The phase 2 trial (TRUST-I, Clinical Trials Identifier: NCT04395677) enrolled 109 patients with locally advanced or metastatic, ROS1-positive NSCLC who were either TKI-naïve or had received prior treatment with crizotinib. 

The patients’ median age was 54 (range, 26-77) years, 93.5% of patients had adenocarcinoma, 26.6% had received chemotherapy, and 22.0% had brain metastases. 

Patients received taletrectinib at 400 mg or 600 mg daily. The primary endpoint was the objective response rate (ORR), and the median follow-up was about 1.5 years.  

In the TKI-naïve patients (n=67), the ORR was 92.5%, and the disease control rate was 95.5%. The median time to response was 1.4 months, the median duration of response was not reached, and the median progression-free survival (PFS) was not reached.

In the crizotinib-pretreated patients (n=38), the ORR was 52.6%, and the disease control rate was 81.6%. The median time to response was 1.4 months, the median duration of response was not reached, and the median PFS was 9.8 months. Among patients with a ROS1 G2032R resistance mutation, the ORR was 80% (4/5).

There were 12 patients with brain metastases — 7 who had received crizotinib and 5 who were TKI-naïve. The intracranial ORR in this group was 91.7%, and the intracranial disease control rate was 100%. 

Dr Li also presented a pooled analysis of phase 1 and phase 2 data. In this cohort, the median PFS was 33.2 months for TKI-naïve patients (n=78) and 11.8 months for crizotinib-pretreated patients (n=46).

Dr Li presented safety results from pooled phase 1 and 2 data for 178 patients who received taletrectinib at 600 mg daily. The median duration of treatment exposure was 7.6 months. 

The most common treatment-emergent adverse events (TEAEs) were increased aspartate aminotransferase (70.8%), increased alanine aminotransferase (64.0%), and diarrhea (61.2%). The rate of TEAEs leading to a dose reduction was 20.2%, and the rate of TEAEs leading to treatment discontinuation was 5.1%. There were no fatal TEAEs.

Based on these results, Dr Li concluded that taletrectinib demonstrated “tolerable safety” and “meaningful clinical efficacy” in both TKI-naïve and crizotinib-pretreated, ROS1-positive NSCLC.

Disclosures: This research was supported by AnHeart Therapeutics, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Li W, Li K, Fan H, et al. Updated efficacy and safety of taletrectinib in patients (pts) with ROS1+ non-small cell lung cancer (NSCLC). ELCC 2023. March 29 – April 1, 2023. Abstract 14MO.