2019 ASCO Annual Meeting!
Session: EGFR and ROS1: Targeting Resistance
Type: Clinical Science Symposium
Time: Friday May 31, 1:00 PM to 2:30 PM
Location: Hall D1
Safety and preliminary clinical activity of repotrectinib in patients with advanced ROS1 fusion-positive non-small cell lung cancer (TRIDENT-1 study).
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 9011)
Author(s): Byoung Chul Cho, Alexander E. Drilon, Robert Charles Doebele, Dong-Wan Kim, Jessica Jiyeong Lin, Jeeyun Lee, Myung-Ju Ahn, Viola Weijia Zhu, Samuel Ejadi, D. Ross Camidge, Yuwei Juliet Liu, Shanna Stopatschinskaja, Jingrong Jean Cui, David Michael Hyman, Sai-Hong Ignatius Ou, Alice Tsang Shaw; Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; Memorial Sloan Kettering Cancer Center, New York, NY; University of Colorado, Denver, CO; Seoul National University Hospital, Seoul, South Korea; Massachusetts General Hospital, Harvard Medical School, Boston, MA; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA; Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA, Orange, CA; University of Colorado Cancer Center, Aurora, CO; Turning Point Therapeutics, Inc, San Diego, CA; Turning Point Therapeutics, San Diego, CA; Turning Point Therapeutics, Inc., San Diego, CA; Chao Family Comprehensive Cancer Center, University of California, Orange, CA; Massachusetts General Hospital/Harvard Medical School, Boston, MA
Background: Repotrectinib is a next-generation ROS1/TRK/ALK TKI inhibiting ROS1 with > 90-fold greater potency than crizotinib. Preclinical studies showed robust kinase inhibitory activity of repotrectinib against all known ROS1 fusion positive resistance mutations, including the most common ROS1 solvent-front mutation (SFM) G2032R. Methods: In this ongoing phase 1 study (NCT03093116), TKI-naïve and TKI-refractory (≥1 TKI) patients (pts) with advanced ROS1/TRK/ALK+ solid tumors received repotrectinib treatment. Endpoints include safety, PK, and confirmed overall response (cORR). Safety analysis for all pts (n = 75) and efficacy analysis for ROS1+ NSCLC pts (n = 28) enrolled on the study was conducted. Results: As of 31-Oct-2018, 75 pts were treated with repotrectinib at dose levels from 40 mg QD to 200 mg BID. Most AEs were manageable and grade (Gr) 1-2. Common ( > 20%) treatment-related AEs were dizziness (49%), dysgeusia (48%), paresthesia (28%), and constipation (20%). Four DLTs (Gr3 dyspnea/hypoxia (n = 1); Gr2 (n = 1) and Gr3 (n = 1) dizziness at 160 mg BID, and Gr3 dizziness (n = 1) at 240 mg QD) occurred and were managed with dose modifications. The MTD has not been reached. Median number of prior TKI treatment was 1 (0-3) with all of TKI naïve and 83% of TKI pre-treated pts received prior chemotherapy. Among 10 evaluable TKI-naïve ROS1+ NSCLC pts, confirmed ORR by Blinded Central Review (BCR) was 90% (95% CI 56 - 100) with median duration of response (DOR) not reached ((range 5.5+ – 14.9+ months (mos)). Among 18 TKI-pretreated pts, confirmed ORR by BCR was 28% (95% CI 10 – 54) with DOR of 10.2 mos. Subgroup analysis showed cORR 44% (95% CI 14 - 79) in 9 prior TKI pts and treated at dose levels of 160 mg QD or above. In 7 pts with measurable target CNS lesions at baseline, the intracranial ORR was 3/3 (100%) with DOR (5.5+; 7.2+; 14.85+ mo) in TKI-naïve pts and 2/4 (50%) with DOR (5.5+;14.8+, mo) in TKI-pretreated pts, respectively. Conclusions: Repotrectinib was well tolerated and demonstrated encouraging overall and intracranial clinical activity in pts with ROS1 fusion-positive NSCLC. Enrollment in phase 1 continues until the RP2D is determined. A global phase 2 study is planned. Clinical trial information: NCT03093116