Reference Detail

Ref Type

abstract

PMID

Authors

Jessica Jiyeong Lin, Alexander E. Drilon, Byoung Chul Cho, Enriqueta Felip, Adrianus De Langen, Nong Yang, Sang-We Kim, Shun Lu, Steven Chuan-Hao Kao, Vamsidhar Velcheti, Denis Lucien MORO SIBILOT, Benjamin J. Solomon, Rafal Dziadziuszko, Matthew G Krebs, Parneet Kaur Cheema, Christophe Alfons Dooms, Shanna Stopatschinskaja, Denise Trone, Felipe Ades, D. Ross Camidge

Title

Intracranial and systemic efficacy of repotrectinib in advanced ROS1 fusion-positive (ROS1+) non-small cell lung cancer (NSCLC) and central nervous system metastases (CNS mets) in the phase 1/2 TRIDENT-1.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of Clinical Oncology	41	16_suppl	2023

URL

https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.9017

Abstract Text

Background: Repotrectinib is a next-generation ROS1 and TRK tyrosine kinase inhibitor (TKI) that has demonstrated durable activity with a manageable safety profile in TKI-naïve and TKI-pretreated patients (pts) with advanced ROS1+ NSCLC. We report the first analysis of outcomes on repotrectinib in pts with ROS1+ NSCLC by baseline (BL) CNS met status in the global pivotal phase 1/2 TRIDENT-1 trial (NCT03093116). Methods: Pts with ROS1+ NSCLC were assigned to 4 cohorts by treatment history: ROS1 TKI-naïve, 1 ROS1 TKI and no chemotherapy (chemo), 1 ROS1 TKI and 1 platinum-based chemo, and 2 ROS1 TKIs and no chemo. Treated or untreated asymptomatic CNS mets were permitted. Brain scans were mandated for all pts in phase 2 at screening and at protocol-specified intervals until progression. Endpoints included confirmed objective response rate (cORR) and duration of response (DOR) by blinded independent central review (BICR; RECIST v1.1); intracranial ORR (icORR) in pts with measurable brain mets at BL by BICR per mRECIST v1.1; and safety. Results: In pts with BL measurable CNS mets who were TKI-naïve (n = 8) and in those with 1 TKI and no chemo (n = 12), icORR (95% CI) was 88% (47-100) and 42% (15-72), respectively. At data cutoff (June 20, 2022), 0 of 7 responders in the TKI-naïve cohort and 2 of 5 in the cohort with 1 prior TKI and no chemo had intracranial progression or death; intracranial DOR range was 1.9-14.8+ mo (TKI-naïve) and 3.0-11.1+ mo (1 TKI and no chemo), with 86% and 80% of pts with an intracranial response remaining on treatment, respectively. Median follow-up and systemic response by CNS met status are shown in the Table. In pts with ROS1+ NSCLC with (n = 118) or without (n = 178) CNS mets, most common any-grade neurologic treatment-emergent adverse events were dizziness (57% / 63%), dysgeusia (42% / 53%), paresthesia (32% / 34%), headache (27% / 12%), ataxia (17% / 22%), and memory impairment (14% / 10%). Conclusions: In TRIDENT-1, repotrectinib showed durable clinical activity in ROS1 TKI-naïve and -pretreated pts with or without BL CNS mets, including intracranial responses. Repotrectinib safety profile was similar in pts with ROS1+ NSCLC with or without CNS mets. Clinical trial information: NCT03093116.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
ROS1 fusion	lung non-small cell carcinoma	sensitive	Repotrectinib	Phase Ib/II	Actionable	In a Phase I/II trial (TRIDENT-1), Augtyro (repotrectinib) treatment resulted in an intracranial objective response rate (icORR) of 88% (7/8) with intracranial duration of response (DOR) ranging from 1.9-14.8 months in non-small cell lung cancer patients harboring ROS1 fusions who were TKI-naive, and an icORR of 42% (5/12) with intracranial DOR ranging from 3.0-11.1 months in those with 1 prior TKI and no chemo (J Clin Oncol 41, 2023 (suppl 16; abstr 9017); NCT03093116).	detail...