Meeting
2023 ASCO Annual Meeting
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.
Authors
Jessica Jiyeong Lin
Massachusetts General Hospital Cancer Center, Boston, MA
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
Organizations
Massachusetts General Hospital Cancer Center, Boston, MA, Memorial Sloan Kettering Cancer Center, New York, NY, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Netherlands Cancer Institute, Amsterdam, Netherlands, Lung & Gastrointestinal Oncology Department, Hunan Cancer Hospital, Changsha, China, Asan Medical Center, University of Ulsan Medical College, Songpa-Gu, South Korea, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China, Chris O'Brien Lifehouse, Camperdown, Australia, NYU Laura & Isaac Perlmutter Cancer Center, New York, NY, Centre Hospitalier Universitaire de Grenoble (France), Grenoble, France, Peter MacCallum Cancer Centre, Melbourne, Australia, Medical University of Gdansk, Gdansk, Poland, University of Manchester and The Christie NHS Foundation Trust, Manchester, United Kingdom, William Osler Health System, University of Toronto, Brampton, ON, Canada, University Hospitals Leuven, Leuven, Belgium, Turning Point Therapeutics Inc, a wholly owned subsidiary of Bristol Myers Squibb Company, San Diego, CA, Bristol Myers Squibb, Princeton, NJ, University of Colorado Anschutz Medical Center, Aurora, CO
Research Funding
Pharmaceutical/Biotech Company
Turning Point Therapeutics Inc, a wholly owned subsidiary of Bristol Myers Squibb Company
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.
| ROS1 TKI naïve n = 71 | 1 TKI and no chemo n = 56 | 1 TKI and 1 chemo n = 26 | 2 TKIs and no chemo n = 18 | |
|---|---|---|---|---|
| Median follow-up, mo | 18.1 | 15.5 | 21.3 | 14.1 |
| Pts with CNS mets, n (%) | 18 (25) | 24 (43) | 10 (38) | 8 (44) |
| cORR, % 95% CI | 89 65-99 | 33 16-55 | 40 12-74 | 13 0.3-53 |
| 6-mo DOR 95% CI | 100 100-100 | 63 29-96 | 50 1-99 | 100 100-100 |
| 12-mo DOR 95% CIa | 93 79-100 | - | - | - |
| Pts without CNS mets, n (%) | 53 (75) | 32 (57) | 16 (62) | 10 (56) |
| cORR, % 95% CI | 76 62-86 | 41 24-59 | 44 20-70 | 40 12-74 |
| 6-mo DOR 95% CI | 87 77-98 | 92 76-100 | 71 38-100 | 50 1-99 |
| 12-mo DOR 95% CIa | 84 72-96 | - | - | - |
aNot reported for TKI-pretreated cohorts due to small n’s at risk.
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Details
Session Type
Poster Discussion Session
Session Title
Lung Cancer—Non-Small Cell Metastatic
Track
Lung Cancer
Sub Track
Metastatic Non–Small Cell Lung Cancer
Clinical Trial Registration Number
NCT03093116
Citation
J Clin Oncol 41, 2023 (suppl 16; abstr 9017)
DOI
10.1200/JCO.2023.41.16_suppl.9017
Abstract #
9017
Poster Bd #
5
Abstract Disclosures
Similar Abstracts
Abstract
2024 ASCO Annual Meeting
REZILIENT3: Phase 3 study of zipalertinib plus chemotherapy in patients with previously untreated, advanced nonsquamous non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertions (ex20ins) mutations.
First Author: Helena Alexandra Yu
Abstract
2020 ASCO Virtual Scientific Program
TRIDENT-1: A global, multicenter, open-label Phase II study investigating the activity of repotrectinib in advanced solid tumors harboring ROS1 or NTRK1-3 rearrangements.
First Author: Robert Charles Doebele
Abstract
2024 ASCO Annual Meeting
FDA analysis of immune checkpoint inhibitors in combination with vascular endothelial growth factor tyrosine kinase inhibitors in the second-line treatment of patients with advanced non-small cell lung cancer.
First Author: Justin Nathaniel Malinou
Abstract
2023 ASCO Annual Meeting
Clinical efficacy analysis of furmonertinib and structural insights into sensitivity to diverse TKIs for NSCLC with EGFR exon 20 insertion.
First Author: Xiao Zhang