Abstract 977P
Background
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.
Methods
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.
Results
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.
Conclusions
Brigatinib demonstrated encouraging antitumor activity in patients with TKI-naïve ROS1-rearranged advanced NSCLC. The safety profile of brigatinib was consistent with previous studies.
Clinical trial identification
Clinical trial information: JapicCTI-194851.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
AMED.
Disclosure
R. Toyozawa: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical, Eli Lilly Japan, Taiho Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical; Financial Interests, Personal, Other, honoraria: AstraZeneca, Takeda Pharmaceutical, MSD, Pfizer Japan; Financial Interests, Institutional, Invited Speaker: AbbVie, Amgen, Takeda Pharmaceutical, Pfizer Japan, Daiichi Sankyo, Eli Lilly Japan, Novartis Pharma. S. Niho: Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Ono, Chugai, Eli Lilly, Takeda. Y. Goto: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant Health Inc., Illumina, MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho, Johnson and Johnson, D3bio; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, MSD, Merck, Novartis, Ono Pharmaceutical, Pfizer, Taiho, Thermo Fischer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Guardant Health, Preferred Network; Financial Interests, Personal and Institutional, Invited Speaker: Chugai, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Prefered Network. T. Takahashi: Financial Interests, Personal, Invited Speaker: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Boehringer Ingelheim Japan, INC, Takeda Pharmaceutical Co Ltd., Yakult Honsha Co. Ltd; Financial Interests, Institutional, Invited Speaker: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Amgen Inc., Merck Biopharma CO., Ltd. K. Ohashi: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Eli Lilly, Novartis Japan; Financial Interests, Personal, Funding: AstraZeneca, Daiichi Sankyo, Eli Lilly; Financial Interests, Personal, Research Grant: Boehringer Ingelheim, Chugai. H. Daga: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, AstraZeneca. H. Tanaka: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Eli Lilly, MSD, Ono Pharmaceutical, Merck, Novartis, Takeda Pharmaceutical, Pfizer, Daiichi Sankyo Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Chugai Pharmaceutical, Merck, AstraZeneca, MSD, Eli Lilly, Ono Pharmaceutical, Bristol Myers Squibb, Merck, Takeda Pharmaceutical, Taiho Pharmaceutical, Pfizer, Daiichi Sankyo Pharmaceutical, AbbVie. Y. Hattori: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Chugai, Eli Lilly, MSD, Nippon Kayaku, Novartis, Ono, Taiho; Financial Interests, Institutional, Invited Speaker: Chugai, Daiichi Sankyo, Janssen Pharmaceutical, MSD, ONO, Takeda. M. Morise: Financial Interests, Personal, Invited Speaker: Chugai, MSD; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Eli Lilly. S. Matsumoto: Financial Interests, Personal, Invited Speaker: Merck Biopharma, Eli Lilly, AstraZeneca, Chugai, Novartis; Financial Interests, Institutional, Invited Speaker: Merck Biopharma, Janssen Pharmaceutical K.K. K. Yoh: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Janssen, Lilly, Taiho, Novartis, Kyowa Kirin, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Lilly, Pfizer, Daiichi Sankyo, AbbVie, Taiho, MSD, Takeda. S. Nomura: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Kyowa Hakko Bio; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca. K. Goto: Financial Interests, Personal, Invited Speaker: Amgen Inc., Amgen K.K., Amoy Diagnostics Co., Ltd., AstraZeneca K.K., Bayer U.S., Boehringer Ingelheim Japan, Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Guardant Health Inc., Merck Biopharma Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K.; Financial Interests, Personal, Expert Testimony: Medpace Japan K.K.; Financial Interests, Personal and Institutional, Funding: Amgen Inc., Amgen K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Haihe Biopharma Co., Ltd., Ignyta, Inc., Janssen Pharmaceutical K.K., Kissei Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Loxo Oncology, Inc., Medical & Biological Laboratories Co., Ltd., Merck Biopharma Co., Ltd., Merus N.V., MSD K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sumitomo Dainippon Pharma Co., Ltd., Spectrum Pharmaceuticals, Inc., Sysmex Corporation., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics, Inc.; Non-Financial Interests, Member: American Society of Clinical Oncology, The Japan Lung Cancer Society, Japanese Society of Medical Oncology, The Japanese Cancer Association. All other authors have declared no conflicts of interest.