Abstract 1361TiP
Background
HER2 mutations are an established molecular target in NSCLC; however, there are no approved therapies for pts with HER2m NSCLC. T-DXd is an antibody-drug conjugate consisting of an anti-HER2 antibody, cleavable linker, and topoisomerase I inhibitor payload. T-DXd is approved globally at a dose of 5.4 mg/kg every 3 weeks (Q3W) in patients with HER2+ metastatic breast cancer and in the US/Japan at 6.4 mg/kg Q3W in patients with HER2+ metastatic gastric cancer. In a ph 2 trial (DESTINY-Lung01; NCT03505710) in pts with relapsed/refractory HER2m NSCLC, who received T-DXd 6.4 mg/kg Q3W, the confirmed objective response rate (ORR) was 61.9% and the median progression-free survival (PFS) was 14 months at the interim analysis (Smit ASCO 2020). Here we describe a ph 2 study to evaluate the efficacy and safety of 2 doses of T-DXd (5.4 mg/kg and 6.4 mg/kg) in pts with relapsed/refractory HER2m NSCLC. This study will further evaluate the 6.4-mg/kg dose and provide the first data on the 5.4-mg/kg dose in this pt population, with a primary objective of confirmed ORR.
Trial design
DESTINY-Lung02 (NCT04644237) is a multicenter, randomized, ph 2 study of T-DXd in pts with HER2m NSCLC. Eligible pts will have metastatic NSCLC with a known activating HER2 mutation (archival or fresh tumor tissue samples), received previous treatment including platinum-based therapy, an ECOG PS of 0 or 1, and ≥1 measurable lesion by RECIST v1.1. Prior anti-HER2 therapies are allowed. Pts are excluded if they have a known driver mutation other than a HER2 mutation (eg, EGFR or BRAF mutation or ALK or ROS1 fusion) or a history of interstitial lung disease. Pts will be randomly assigned (2:1) to receive T-DXd, 5.4 mg/kg Q3W or 6.4 mg/kg Q3W, respectively. Randomization will be stratified by pts who received prior anti−PD-1/PD-L1 treatment (yes/no). Enrollment began in March 2021, with ∼150 pts planned to be enrolled at ∼45 sites. The primary endpoint is confirmed ORR based on blinded independent central review. Additional endpoints include ORR based on investigator assessment, duration of response, disease control rate, PFS, overall survival, safety, pharmacokinetics, immunogenicity, and health-related quality of life.
Clinical trial identification
NCT04644237.
Editorial acknowledgement
Under the guidance of authors, assistance in medical writing and editorial support was provided by Cindy M. Rigby, PhD, of ApotheCom and funded by Daiichi Sankyo, Inc.
Legal entity responsible for the study
Daiichi Sankyo, Inc.
Funding
Daiichi Sankyo, Inc., and AstraZeneca.
Disclosure
E.F.F. Smit: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Bayer, Celgene, DSI, Eli Lilly, MSD, Merck, Novartis, Pfizer, Takeda, Regeneron, Roche Genentech, Roche Diagnostics. All institutional; Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Merck, MSD, Roche, Genentech. B.T. Li: Non-Financial Interests, Personal, Advisory Role: Daiichi Sankyo, AstraZeneca, Amgen, Genentech, Boehringer Ingelheim, Lilly; Financial Interests, Institutional, Research Grant: Amgen, Genentech, AstraZeneca, Daiichi Sankyo, Lilly, Illumina, GRAIL, Guardant Health, Hengrui Therapeutics, MORE Health and Bolt Biotherapeutics; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Resolution Bioscience, MORE Health, and Jiangsu Hengrui Medicine; Financial Interests, Personal, Licensing Fees: at Karger Publishers, Shanghai Jiao Tong University Press. J. Mazieres: Financial Interests, Personal, Other, Honoraria: Roche, BMS, MSD, AstraZeneca, Takeda, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche, Pierre Fabre, AstraZeneca. D. Planchard: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Samsung; Financial Interests, Institutional, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Samsung; Financial Interests, Personal, Other, Travel expenses: AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer. K. Nakagawa: Financial Interests, Personal, Other, Honoraria: Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Nanzando Co., Ltd, AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Roche Diagnostics K.K., MSD K.K., Eli Lilly Japan K.K., Nippon Kayaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer; Financial Interests, Personal, Advisory Role: Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc., KYORIN Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Research Grant: MSD K.K., AstraZeneca K.K., Pfizer Japan Inc., ICON Japan K.K., Astellas Pharma Inc., Bayer Yakuhin, Ltd., Takeda Pharmaceutical Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., EPS International Co., Ltd., Bayer Yakuhin, Ltd., Bri. K. Goto: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo Co., Ltd.; Financial Interests, Personal, Research Grant: Daiichi Sankyo Co., Ltd. L. Paz-Ares: Financial Interests, Personal, Speaker’s Bureau: Roche, MSD, Merck Serono, BMS, AstraZeneca, Eli Lilly, Pfizer, PharmaMar, Bayer, AbbVie, Amgen, Janssen, GSK, Novartis, Ipsen, Boehringer Ingelheim, Takeda, Sanofi, Blueprint, Mirati; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, PharmaMar. S. Novello: Financial Interests, Personal, Advisory Role: AstraZeneca, BI, Beigene, MSD, Eli Lilly, Takeda, Pfizer, Roche, Amgen, Sanofi, BMS; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, BI, Beigene, MSD, Eli Lilly, Takeda, Pfizer, Roche, Amgen, Sanofi, BMS. J.C-H Yang: Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Roche, MSD, Pfizer, Novartis, BMS, AstraZeneca, Takeda Oncology; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Eli Lilly, Bayer, Roche, MSD, Pfizer, Novartis, BMS, Ono Pharmaceutical, AstraZeneca, Merck Serono, Yuhan Pharmaceutical, Daiichi Sankyo, Takeda Oncology, Amgen, Janssen, Eisai. M-J. Ahn: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Takeda, MSD, Ono, BMS, Lilly, Amgen, Merck, Roche; Financial Interests, Institutional, Advisory Role: AstraZeneca, Takeda, MSD, Ono, BMS, Lilly, Amgen, Merck, Roche, Alpha Pharmaceuticals; Financial Interests, Personal, Research Grant: AstraZeneca, Roche. G. Liu: Financial Interests, Personal, Advisory Role: Pfizer, Novartis, AstraZeneca, Takeda, BMS, Roche, Bayer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Takeda, Pfizer; Financial Interests, Institutional, Research Grant: Takeda, AstraZeneca, Boehringer Ingelheim. K. O'Byrne: Financial Interests, Personal, Other, Honoraria: Pfizer, Roche, AZ, Boehringer Ingelheim, BMS, MSD, Novartis, Teva, Janssen, Natera, Yuhan; Financial Interests, Personal, Advisory Role: Pfizer, Roche, AZ, Boehringer Ingelheim, BMS, MSD, Novartis, Teva, Janssen, Natera, Yuhan, TriStar; Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, BMS, Boehringer Ingelheim, MSD, Pfizer, Foundation Medicine; Financial Interests, Personal, Stocks/Shares: Carpe Vitae Pharmaceuticals, RepLuca Pharmaceuticals and DGC Diagnostics; Financial Interests, Institutional, Research Grant: Carpe Vitae Pharmaceuticals, RepLuca Pharmaceuticals; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Roche, BMS, MSD, Boehringer Ingelheim (conference attendance/presentations); Financial Interests, Personal, Licensing Fees: Carpe Vitae Pharmaceuticals, RepLuca Pharmaceuticals (Intellectual property/patents); Financial Interests, Personal, Member of the Board of Directors: Carpe Vitae Pharmaceuticals Board Member; Financial Interests, Personal, Other, Non-remunerated activity/ies: Convenor and co-convenor of academic meetings supported by pharm and biotech companies. M. Aregay: Financial Interests, Personal, Other, Full/Part-time employment: Daiichi Sankyo Co., Ltd.; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo Co., Ltd. R. Shiga: Financial Interests, Personal, Other, Full/Part-time employment: Daiichi Sankyo, Inc. K. Saxena: Financial Interests, Personal, Other, Full/Part-time employment: Daiichi Sankyo, Inc. G. Meinhardt: Financial Interests, Personal, Other, Full/Part-time employment: Daiichi Sankyo, Inc.; Financial Interests, Personal, Stocks/Shares: Bayer, Daiichi Sankyo. P.A. Jänne: Financial Interests, Personal, Advisory Role: Pfizer, Boehringer Ingelheim, AstraZeneca, Merrimack, Chugai Pharma, Roche/Genentech, Loxo, Mirati Therapeutics, Araxes Pharma, Ignyta, Lilly, Takeda, Novartis, Biocartis, Voronoi Health Analytics, SFJ Pharmaceuticals Group, Sanofi, Biocartis, Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Gatekeeper Pharmaceuticals, Loxo; Financial Interests, Personal, Research Grant: AstraZeneca, Astellas Pharma, Daiichi Sankyo, Lilly, Boehringer Ingelheim, Puma Biotechnology, Takeda, Revolution Medicines; Financial Interests, Personal, Licensing Fees: I am a co-inventor of DFCI owned patent on EGFR mutations licensed to Lab Corp. I receive post-marketing royalties from this invention.