Repotrectinib in <i>ROS1</i> Fusion–Positive Non–Small-Cell Lung Cancer

Репотрецтиниб при немелкоклеточном раке легкого с ROS1-реаранжировкой
Rafał Dziadziuszko, Enriqueta Felip, Shun Lü, Byoung Chul Cho, Misako Nagasaka, Nong Yang, D. Ross Camidge, Benjamin Solomon, Ki Hyeong Lee, Alexander Drilon, Matthew Krebs, W. Marston Linehan, Vamsidhar Velcheti, Sanjay Popat, Minal Mehta, Jürgen Wolf, Muhammad Shaalan Beg, Yong Yuan, Kōichi Goto, Christoph Springfeld, Denis Moro‐Sibilot, Benjamin Besse, Sang‐We Kim, Christophe Dooms, Parneet Cheema, Steven Kao, Adrianus J. de Langen, Wenxiu Yao, Xiufeng Hu, Shanna Stopatschinskaja, Denise Trone, Armin Graber, Gregory E. Sims
2024-01-10

G2032R mutationPhase 2 TRIDENT-1 trial (NCT03093116)ROS1 fusion–positive non–small-cell lung cancerRepotrectinibTreatment-related adverse events (dizziness, dysgeusia, paresthesia)
BACKGROUND: G2032R. METHODS: fusion-positive NSCLC. The primary efficacy end point in the phase 2 trial was confirmed objective response; efficacy analyses included patients from phase 1 and phase 2. Duration of response, progression-free survival, and safety were secondary end points in phase 2. RESULTS: G2032R mutation had a response. A total of 426 patients received the phase 2 dose; the most common treatment-related adverse events were dizziness (in 58% of the patients), dysgeusia (in 50%), and paresthesia (in 30%), and 3% discontinued repotrectinib owing to treatment-related adverse events. CONCLUSIONS: fusion-positive NSCLC, regardless of whether they had previously received a ROS1 TKI. Adverse events were mainly of low grade and compatible with long-term administration. (Funded by Turning Point Therapeutics, a wholly owned subsidiary of Bristol Myers Squibb; TRIDENT-1 ClinicalTrials.gov number, NCT03093116.).
1
Among 426 patients receiving the phase 2 dose, the most common treatment-related adverse events were dizziness (58%), dysgeusia (50%), and paresthesia (30%).
2
Efficacy analyses pooled patients from phase 1 and phase 2, with secondary end points including duration of response and progression-free survival.
3
Repotrectinib demonstrated activity in ROS1 fusion–positive NSCLC regardless of prior receipt of a ROS1 tyrosine kinase inhibitor.
4
Repotrectinib induced responses in tumors harboring the ROS1 G2032R resistance mutation.
5
Repotrectinib showed confirmed objective responses in patients with ROS1 fusion–positive non–small-cell lung cancer enrolled in the trial.
6
Treatment-related adverse events led to discontinuation of repotrectinib in 3% of patients, and most adverse events were low grade and compatible with long-term administration.

Repotrectinib treatment in ROS1 fusion–positive non–small-cell lung cancer patients

Efficacy (confirmed objective response, duration of response, progression-free survival) and safety (treatment-related adverse events, discontinuation rates) of repotrectinib in ROS1 fusion–positive NSCLC, including patients with prior ROS1 TKI exposure and G2032R mutation responses

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2024-01-10
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Authors
Rafał Dziadziuszko
Enriqueta Felip
Shun Lü
Byoung Chul Cho
Misako Nagasaka
Nong Yang
D. Ross Camidge
Benjamin Solomon
Ki Hyeong Lee
Alexander Drilon
Matthew Krebs
W. Marston Linehan
Vamsidhar Velcheti
Sanjay Popat
Minal Mehta
Jürgen Wolf
Muhammad Shaalan Beg
Yong Yuan
Kōichi Goto
Christoph Springfeld
Denis Moro‐Sibilot
Benjamin Besse
Sang‐We Kim
Christophe Dooms
Parneet Cheema
Steven Kao
Adrianus J. de Langen
Wenxiu Yao
Xiufeng Hu
Shanna Stopatschinskaja
Denise Trone
Armin Graber
Gregory E. Sims
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