Repotrectinib monotherapy resulted in high objective response rates (ORR) in a cohort of patients with advanced ROS1 fusion-positive non-small cell lung cancer (NSCLC), according to updated results from the phase 2 expansion 1 (EXP-1) cohort of the  TRIDENT-1 study. The data were presented at the 2020 World Conference on Lung Cancer in Singapore.

“Preliminary TRIDENT-1 data support repotrectinib as a potential best-in-class treatment in ROS1-positive advanced NSCLC,” said lead author Byuong Chul Cho, MD, PhD, who presented the findings.

In the phase 1/2 TRIDENT-1 study (NCT03093116), investigators administered repotrectinib to patients with advanced ROS1-positive NSCLC across 4 cohorts. Previously reported phase 1 data demonstrated an ORR of 91% and a median duration of response (DOR) of 23.1 months with the monotherapy. The updated analysis included 15 patients who received the phase 2 dose of repotrectinib.

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At baseline, the median patient age was 58 years and 60% of patients had an Eastern Cooperative Oncology Group performance status of 1. Twenty percent of the cohort received prior chemotherapy.

At the data cutoff of December 31, 2020, the confirmed ORR was 93% (95% CI, 68-100), which included 1 unconfirmed partial response (PR). A second post-baseline scan is awaited to confirm the PR.

Repotrectinib was found to be well-tolerated. The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2 in nature, and the most common TRAEs were dizziness (58.4%, all grades) and dysgeusia (43.2%, all grades). There were no grade 5 TEAEs. TEAEs led to the discontinuation of the study drug among 8.6% of patients; 17.8% required a dose reduction.

On December 8, 2020, Turning Point Therapeutics Inc., repotrectinib’s developer, announced that the U.S. Food and Drug Administration had granted the agent a breakthrough therapy designation for patients with metastatic, ROS1-positive NSCLC who had not received prior tyrosine kinase inhibitor therapy.

The “updated phase 2 data continues to support strong clinical activity in TKI-naïve patients,” Cho concluded.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.


Cho BC, Doebele RC, Lin JJ, et al. Phase 1/2 TRIDENT-1 study of repotrectinib in patients with ROS1+ or NTRK+ advanced solid tumors. Presented at: 2020 World Conference on Lung Cancer Singapore; January 28-31, 2020. Abstract MA11.07.