Background

DESTINY-Lung01 (NCT03505710) is a multicenter, phase II study evaluating the safety and efficacy of T-DXd (HER2 antibody-drug conjugate) in pts with HER2-OE or HER2-mutated unresectable and/or metastatic NSCLC. We report the results of T-DXd in pts with HER2-OE NSCLC.

Methods

Pts with pretreated metastatic NSCLC with HER2 immunohistochemistry (IHC) 3+ or 2+ (without known HER2 mutation) received T-DXd 6.4 mg/kg (cohort 1) or 5.4 mg/kg (cohort 1a) every 3 weeks. Primary endpoint was confirmed objective response rate (ORR) by independent central review (ICR). Additional endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and evaluation of safety.

Results

As of Dec 3, 2021, 49 and 41 pts were enrolled in cohorts 1 and 1a. Central nervous system metastases at baseline were present in 17 (34.7%; cohort 1) and 12 (29.3%; cohort 1a) pts. Median number of prior treatment regimens was 3 (range, 1-8 [cohort 1] and 1-5 [cohort 1a]); median treatment duration was 4.1 months (mo) (range, 0.7-27.8) and 5.5 mo (range, 0.7-16.5) in cohorts 1 and 1a, respectively. ORR by ICR was 26.5% and 34.1% (table), median PFS was 5.7 mo and 6.7 mo, and median OS was 12.4 mo and 11.2 mo in cohorts 1 and 1a, respectively. All pts had at least 1 treatment-emergent adverse event (TEAE) and the most common were nausea (59.2% and 73.2%), decreased appetite (44.9.% and 46.3%), and fatigue (32.7% and 51.2%); grade (G) ≥3 TEAEs occurred in 81.6% and 51.2% of pts (drug-related, 53.1% and 22.0%) in cohorts 1 and 1a, respectively. Independently adjudicated drug-related interstitial lung disease (ILD) (any G) occurred in 20.4% (2 G1, 5 G2, 3 G5; cohort 1) and 4.9% (1 G1, 1 G5; cohort 1a) of pts. Table: 975P

Efficacy and safety of T-DXd in pts with HER2-OE NSCLC

Conclusions

Both T-DXd doses had encouraging and consistent antitumor activity in heavily pretreated pts with HER2-OE NSCLC. T-DXd 5.4 mg/kg was associated with a better safety profile vs the 6.4-mg/kg dose.

Clinical trial identification

NCT03505710.

Editorial acknowledgement

Under the guidance of authors, medical writing and editorial support was provided by Toinette Labuschagné, MSc, and Andre Wang, PharmD, of ApotheCom and was funded by Daiichi Sankyo.

Legal entity responsible for the study

Daiichi Sankyo and AstraZeneca.

Funding

Daiichi Sankyo and AstraZeneca.

Disclosure

E.F. Smit: Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, MSD, Boehringer Ingelheim, Roche, BMS, Eli Lilly, Takeda, Sanofi, Janssen; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Institutional, Invited Speaker: Pfizer, Gilead, AZ, Genmab. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith Kline, Janssen, Medical Trends, Merck Sharp & Dohme, Pfizer, Puma, Sanofi, Takeda, Merck Serono, Peptomyc, Regeneron, Syneos Health, F. Hoffmann-La Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dome, Peervoice, Pfizer, Springer, Touch Medical, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono; Financial Interests, Personal, Invited Speaker, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme Corp, AstraZeneca AB, Daiichi Sankyo Inc, Exelixis Inc, Merck KGAA, Janssen Cilag International NV, GlaxoSmithKline Research & Development Limited, AbbVie Deutschland GmbH & Co KG, Novartis Farmaceutica SA, Bayer Consumer Care AG, Takeda Pharmaceuticals International, Boehringer Ingelheim International GmbH, Pfizer S.L.U., Amgen Inc, Bristol Myers Squibb International Corporation (BMS), Mirati Therapeutics Inc; Non-Financial Interests, Leadership Role, President Elect (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of ESMO Nominating Committee and Compliance Committee: ESMO; Non-Financial Interests, Leadership Role, Member of Board of Directors and the Executive Committee (2017-Sept 2021): IASLC (International Association for the Study of Lung Cancer); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). D. Uprety: Financial Interests, Personal, Advisory Role, Honoraria: Daiichi Sankyo, AstraZeneca. K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Nippon Kayaku Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., CMIC ShiftZero K.K., Life Technologies Japan Ltd., Neo Communication, Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., 3H Clinical Trial Inc., Care Net, Inc., Medical Review Co., Ltd., Medical Mobile Communications co., Ltd, Yodosha Co., Ltd., Nikkei Business Publications, Inc., Japan Clinical Research Operations, CMIC Co., Ltd., Novartis Pharma K.K., Taiyo Pharma Co., Ltd.; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K.; Financial Interests, Institutional, Other, patents sales fee: Daiichi Sankyo Co., Ltd.; Financial Interests, Institutional, Research Grant: PAREXEL International Corp., PRA Health Sciences, EPS Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co., Ltd,., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., IQVIA Services JAPAN K.K., Syneos Health Clinical K.K., Nippon Kayaku Co., Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan Clinical Research Operations, Takeda Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Sysmex Corporation, Medical Research Support, Eli Lilly Japan K.K., Amgen Inc., Novartis Pharma K.K., Novartis Pharma K.K., SRL, Inc. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daichii, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-Cilag International NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President. ASEICA (Spanish Association of Cancer Research); Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. J. Pacheco: Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Institutional, Other, Honoraria: Genentech, Takeda; Financial Interests, Personal, Advisory Role, Honoraria: AstraZeneca, Gerson Lehrman Group, Hengrui Pharmaceuticals, Silverback Therapeutics, Novartis, Pfizer, Takeda; Financial Interests, Personal, Other, Travel expenses, including accommodations: Daichii Sanyko, Checkmate Pharmaceuticals, Pfizer. B.T. Li: Non-Financial Interests, Personal, Advisory Role, Honoraria: Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Genentech, Lilly; Financial Interests, Personal, Other, Travel expenses, including accommodations: Jiangsu Hengrui Medicine, More Health; Financial Interests, Institutional, Research Grant, Honoraria: Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui USA, Lilly. D. Planchard: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Janssen, AbbVie; Financial Interests, Institutional, Other: AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo, Janssen, AbbVie; Financial Interests, Other, Travel expenses, including accommodations: AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer. C. Baik: Financial Interests, Advisory Role, Honoraria: AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Takeda, Turning Point Therapeutics, Regeneron, Guardant Health, Silverbac Therapeutics; Financial Interests, Research Grant, Honoraria: Loxo, AstraZeneca, Pfizer, Spectrum Pharmaceuticals, Blueprint Medicines, Daiichi Sankyo, Rain Therapeutics, AbbVie, TP Therapeutics, Lilly Oncology, Janssen. Y. Goto: Financial Interests, Personal, Other, Honoraria: Chugai, Taiho, Boehringer Ingelheim, Ono, Bristol Myers Squibb, Pfizer, MSD, Novartis, Merck, Thermo Fischer, AstraZeneca, Kyowa Kirin, MSD, Creative therapeutical, GSK, Taiho, Chugai, Novartis, Eli Lilly, Johnson & Johnson, Guardant, Nippon Kayaku, Daiichi Sankyo, BMS, Janssen, Towa, Takeda; Financial Interests, Institutional, Advisory Role, Honoraria: AstraZeneca, Chugai, Boehringer Ingelheim, Eli Lilly, Taiho, Pfizer, Novartis, Guardant Health Inc., Illumina, Daiichi Sankyo, Ono Pharmaceutical, Bristol Myers Squibb, MSD; Financial Interests, Institutional, Leadership Role, Honoraria: Cancer Net Japan, JAMT; Financial Interests, Institutional, Research Grant, Honoraria: IQVIA, MSD, Novartis, Pfizer, Mebix, CReS Kyushu, Daiichi Sankyo, Chugai. H. Murakami: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Chugai pharma, Takeda, Daiichi Sankyo, AbbVie, Ono Pharmaceutical, Bristol Myers Squibb Japan, MSD, Pfizer, Novartis, Lilly Japan, Taiho Pharmaceutical, Boehringer Ingelheim, Eisai, Nihon Kayaku; Financial Interests, Institutional, Advisory Role, Honoraria: Chugai pharma, GAIA BioMedicine; Financial Interests, Institutional, Research Grant, Honoraria: AstraZeneca, Chugai pharma, Takeda, Daiichi Sankyo, AbbVie, IQvia. A. Saltos: Financial Interests, Personal, Advisory Role, Honoraria: Daiichi Sankyo; Financial Interests, Advisory Role, Honoraria: Eli Lilly; Financial Interests, Institutional, Research Grant, Honoraria: Daiichi Sankyo, Novartis, Genentech, BioAtla, Memgen, Turning Point Therapeutics, AstraZeneca, Mersana, Genmab. K. Saxena: Financial Interests, Personal and Institutional, Full or part-time Employment: Daiichi Sankyo. R. Shiga: Financial Interests, Full or part-time Employment: Daiichi Sankyo. Y. Cheng: Financial Interests, Full or part-time Employment: Daiichi Sankyo. Q. Yan: Financial Interests, Full or part-time Employment: Daiichi Sankyo. W. Feng: Financial Interests, Full or part-time Employment: Daiichi Sankyo. P.A. Jänne: Financial Interests, Personal, Advisory Board, Consulting fees for advice on drug development: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Chugai Pharmaceuticals, Eli Lilly, Voronoi, Daiichi Sankyo, Novartis, Sanofi, Takeda Oncology, Mirati Therapeutics, Transcenta, Silicon Therapeutics, Syndax, Nuvalent, Bayer, Esai, Allorion Therapeutics, Accutar Biotech, AbbVie; Financial Interests, Personal, Advisory Board, Consulting fees for advice on diagnostic development: Biocartis; Financial Interests, Personal, Stocks/Shares: Gatekeeper Pharmaceuticals, Allorion Therapeutics; Financial Interests, Personal, Royalties, I receive post-marketing royalties from being an inventor on a DFCI owned patent on EGFR mutations licensed to Lab Corp: Lab Corp; Financial Interests, Institutional, Research Grant, Sponsored research agreement with my institution: AstraZeneca, Daiichi Sankyo, PUMA, Eli Lilly, Boehringer Ingelheim, Revolution Medicines, Takeda Oncology.