LBA45 - Primary data from DESTINY-Lung01: A phase II trial of trastuzumab deruxtecan (T-DXd) in patients (Pts) with HER2-mutated (HER2m) metastatic non-small cell lung cancer (NSCLC)

Background

HER2 mutations occur in ∼3% of NSCLC; there are no HER2-targeted therapies approved for pts with NSCLC, representing a high unmet need. DESTINY-Lung01 (NCT03505710) assessed the efficacy and safety of T-DXd, a HER2 antibody-drug conjugate, in pts with HER2m NSCLC.

Methods

In a multicenter, 2-cohort phase 2 trial, pts with HER2m NSCLC refractory to standard treatment received T-DXd 6.4 mg/kg. Primary endpoint was ORR per RECIST v1.1 by independent central review (ICR). Secondary endpoints include duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory biomarkers of HER2 alterations were analyzed.

Results

Ninety-one pts with HER2m NSCLC were enrolled (data cutoff, May 3, 2021). Median follow-up was 13.1 mo. Median age was 60 years. 93.4% of pts had a HER2 kinase domain mutation; 36.3% had asymptomatic central nervous system (CNS) metastasis not requiring ongoing treatment. Median number of prior cancer therapies was 2 (range, 0-7), including platinum-based therapy (94.5%) and PD-1/PD-L1 therapy (65.9%). Centrally confirmed ORR was 54.9% (95% CI, 44.2-65.4). Efficacy was consistent across subgroups, including pts previously treated with a HER2 TKI or with CNS metastasis. Treatment-related adverse events (TRAEs) occurred in 96.7% pts. Adjudicated drug-related interstitial lung disease (ILD) occurred in 24 pts (3 grade 1, 15 grade 2, 4 grade 3, 2 grade 5). Additional biomarker analyses showed responses across different HER2m subtypes, as well as in pts with no detectable HER2 expression or HER2 gene amplification. Table: LBA45

Efficacy and safety of T-DXd in pts with HER2m NSCLC

Conclusions

T-DXd demonstrated robust and durable activity in pts with previously treated HER2m NSCLC, with a manageable safety profile consistent with previous studies. This study provides compelling evidence of positive benefit/risk balance for T-DXd and supports its establishment as a potential new treatment standard for this population.

Clinical trial identification

NCT03505710.

Editorial acknowledgement

Under the guidance of authors, medical writing and editorial support was provided by Cindy M. Rigby, PhD, and Charlene Rivera, PhD, of ApotheCom and was funded by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo, Inc., and AstraZeneca.

Funding

Daiichi Sankyo, Inc. and AstraZeneca.

Disclosure

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: Karger Publishers, Shanghai Jiao Tong University Press (intellectual property as book author). E.F.F. Smit: Financial Interests, Institutional, Advisory Role: AstraZeneca , Bristol Myers Squibb, Bayer, Cellgene, DSI, Eli Lilly, MSD, Merck, Novartis, Pfizer, Takeda, Regeneron, Roche Genentech, Roche Diagnostics; Financial Interests, Institutional, Research Grant: AstraZeneca , Bristol Myers Squibb, Merck, MSD, Roche Genentech. Y. Goto: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Ono Pharmaceutical, Taiho, Chugai, Novartis, Eli Lilly, Pfizer, Daiichi Sankyo, Bristol Myers Squibb, Merck, Thermo Fischer, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Eli Lilly, AstraZeneca, Chugai, Taiho, Boehringer Ingelheim, Ono Pharmaceutical, Bristol Myers Squibb, Pfizer, MSD, Novartis, Daiichi Sankyo, Illumina, Guardant Health Inc.; Non-Financial Interests, Institutional, Research Grant: AbbVie, Eli Lilly, Bristol Myers Squibb, DaiichiSankyo, Prefered Network; Financial Interests, Personal and Institutional, Research Grant: Pfizer, Chugai, Novartis, . 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 Y; 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. J. Mazieres: Financial Interests, Personal, Other, Honoraria: Roche, BMS, MSD, AstraZeneca, Takeda, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche, Pierre Fabre, AstraZeneca. M. Nagasaka: Financial Interests, Personal, Advisory Role: AstraZeneca, Caris, Daiichi Sankyo, Takeda, Novartis, EMD Serono, JNJ, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Blueprint Medicines; Financial Interests, Personal, Other, Travel expenses: An Heart Therapeutics. L. Bazhenova: Financial Interests, Institutional, Other, Honoraria: AstraZeneca, Takeda; Financial Interests, Personal, Advisory Role: Neuvogen, Janssen, Daichi Sankyo, Boehringer Ingelheim, Merck, Regeneron, Bristol Myers Squibb, Novartis; Financial Interests, Institutional, Research Grant: Beyondspring. A.N. Saltos: Financial Interests, Personal, Other, Honoraria: MJH Life Sciences; Financial Interests, Institutional, Research Grant: Novartis, Daiichi Sankyo, Lilly, Mersana, Genmab, AstraZeneca, Turning Point Therapeutics. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Beigene, Boehringer-Ingelheim, BMS, Eli Lilly, F. Hoffman-La Roche, Glaxo Smith Kline, Janssen, Medical Trends, Merck Sharp and Dohme, Merck Serono, Peptomyc, Pfizer, Puma, Regeneron, Sanofi, Syneos Health, Takeda; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, BMS, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Peervoice, Pfizer, Springer, Touch Medical. J.M. Pacheco: Financial Interests, Institutional, Other, Honoraria: Takeda, Genentech; Financial Interests, Personal, Advisory Role: AstraZeneca, Blueprint Medicines, Gerson Lehrman Group, Hengrui Pharmaceuticals, Jazz Pharmaceuticals, Novartis, Pfizer, Takeda, Research America; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Daiichi Sankyo, AstraZeneca, Novartis, Pfizer, Takeda; Financial Interests, Institutional, Research Grant: Pfizer. M. Pérol: Financial Interests, Personal, Other, Honoraria: Roche, Genentech, Eli Lilly, Pfizer, Boehringer-Ingelheim, Clovis Oncology, Merck Sharp & Dome, Bristol Myers Squibb, Novartis, Pierre Fabre, AstraZeneca, Takeda, Sanofi, GlaxoSmithKline, Gritstone; Financial Interests, Personal, Advisory Role: Roche, Genentech, Eli Lilly, Pfizer, Boehringer-Ingelheim, Clovis Oncology, Merck Sharp & Dome, Bristol Myers Squibb, Novartis, Pierre Fabre, AstraZeneca, Takeda, Sanofi, GlaxoSmithKline, Gritstone; Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca; Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, Boehringer-Ingelheim, Takeda, Chugai; Financial Interests, Personal, Other, Travel/Accomodations/Expenses: Roche, Genentech, Eli Lilly, Pfizer, Boehringer-Ingelheim, Merck Sharp & Dome, Bristol Myers Squibb, AstraZeneca, Takeda. L. Paz-Ares: Financial Interests, Personal, Speaker’s Bureau: Roche, MSD, Merck Serono, BMS, AstraZeneca, Lilly, Pfizer, Pharmamar, Bayer, AbbVie, Amgen, Janssen, GSK, Novartis, Ipsen, Boerhinger, Takeda, Sanofi, Blueprint, Mirati; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Pharmamar. K. Saxena: Financial Interests, Personal, Other, Full/Part-time employment: Daiichi Sankyo, Inc. R. Shiga: Financial Interests, Personal, Other, Full/Part-time employment: Daiichi Sankyo, Inc. Y. Cheng: Financial Interests, Personal, Other, Full/Part-time employment: Daiichi Sankyo, Inc. S. Acharyya: Financial Interests, Personal, Other, Full/Part-time employment: Daiichi Sankyo, Inc. J. Shahidi: Financial Interests, Personal, Other, Full/Part-time employment: Daiichi Sankyo, Inc. 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, Medimmun, 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. 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 San; 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, Royalties: I am a co-inventor of DFCI owned patent on EGFR mutations licensed to Lab Corp. I receive post-marketing royalties from this invention. All other authors have declared no conflicts of interest.