977P Phase II study of brigatinib in patients with tyrosine kinase inhibitor (TKI)-naïve ROS1-rearranged advanced non-small cell lung cancer (NSCLC): Barossa cohort 1

Abstract

Barossa is a multicenter, phase II basket study of brigatinib in patients with ROS1-rearranged solid tumors. We report the results of the cohort 1, in which TKI-naïve ROS1-rearranged NSCLC patients were enrolled. Patients with advanced, TKI-naïve ROS1-rearranged advanced NSCLC received brigatinib at a dose of 180 mg once daily with a 7-day lead-in period at 90 mg. The primary end point was objective response rate (ORR; RECIST 1.1) by independent review. Key secondary endpoints were PFS, OS, and safety. The sample size was set at 28 patients, with a one-sided alpha of 0.05, beta of 0.2, and threshold and expected values for primary endpoint of 50% and 75%, respectively. Between September 2019 and May 2020, 28 patients were enrolled from 9 institutions. Baseline characteristics as follows: median age (range): 65 (38-81) years; women, n=18 (64%); ECOG PS of 0-1, n=28 (100%); never smoker, n= 16 (57%); tumor histopathological type: adenocarcinoma, n=27 (96%); brain metastasis, n=8 (29%). The median duration of follow-up for PFS was 9.3 months. Seventeen patients (61%) continued study treatment at the data cutoff date of 30 Nov 2021. The primary endpoint was met as 19 patients achieved PR with ORR at 67.9% (90%CI, 50.6-82.1%). Another 3 patients achieved SD and the disease control rate was 78.6% (95%CI, 59.0-91.7%). The PFS and OS were not yet mature: the median PFS was 12.0 months (95% CI, 5.8-not evaluable). Twenty-five out of the 28 patients remained alive at the data cutoff. Grade 3 pneumonitis, which was considered treatment-related, was observed in 3 patients (10.7%), and all 3 cases resulted in treatment discontinuation. Pneumonitis was improved with steroid therapy in all 3 patients. Other grade ≥3 TRAEs were CPK increased (28.6%), hypertension (21.4%), AST increased (10.7%), ALT increased (7.1%), nausea (3.6%), hyperglycemia (3.6%). No treatment-related deaths were observed. Brigatinib demonstrated encouraging antitumor activity in patients with TKI-naïve ROS1-rearranged advanced NSCLC. The safety profile of brigatinib was consistent with previous studies.