Abstract 976P
Background
In the primary analysis of DESTINY-Lung01 (NCT03505710; data cutoff May 3, 2021), T-DXd (a HER2-targeting antibody–drug conjugate) in pts with previously treated HER2m NSCLC had a confirmed objective response rate (ORR) of 55% (95% CI, 44-65) and a safety profile generally consistent with previous reports (Li N Engl J Med 2021). This update provides additional subgroup analyses and longer follow-up in all pts.
Methods
Pts with HER2m NSCLC refractory to standard therapy received T-DXd 6.4 mg/kg IV Q3W. Primary endpoint was ORR per RECIST v1.1 by independent central review (ICR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety.
Results
At data cutoff (December 3, 2021), 91 pts with HER2m NSCLC were assessed. At baseline, 36.3% had asymptomatic central nervous system metastasis (CNS met); 33.0% had >2 prior therapies; 94.5% had prior platinum-based chemotherapy (CT). Median follow-up and treatment duration were 16.7 and 6.9 mo, respectively. The table shows primary endpoint for the overall and subgroup populations, including pts with CNS met. In the overall population, median PFS was 8.2 mo (95% CI, 6.0-11.9); median OS was 18.6 mo (95% CI, 13.8-25.8); median DOR was 10.6 mo (5.8-17.7); DCR was 92.3% (95% CI, 84.8-96.9). Drug-related treatment-emergent adverse events (TEAEs) occurred in 88 (96.7%) pts. The most common TEAEs were nausea (76.9%), vomiting (47.3%), and alopecia (46.2%). Adjudicated drug-related interstitial lung disease occurred in 25 (27.5%) pts (3 grade [G] 1, 16 G 2, 4 G 3, 2 G 5). Table: 976P
T-DXd efficacy in HER2m NSCLC
| Overall N = 91 | Prior therapy | CT n = 86 | CT and anti–PD-(L)1 n = 57 | CNS met | HER2 KD mut n = 85 | |||
| ≤2 lines n = 61 | >2 lines n = 30 | Yes n = 33 | No n = 58 | |||||
| ORR by ICR, n (%) 95% CI | 50 (54.9) 44.2-65.4 | 34 (55.7) 42.5-68.5 | 16 (53.3)34.3-71.7 | 46 (53.5) 42.4-64.3 | 37 (64.9) 51.1-77.1 | 18 (54.5) 36.4-71.9 | 32 (55.2) 41.5-68.3 | 49 (57.6) 46.5-68.3 |
| Complete response | 1 (1.1) | NA | 1 (1.2) | 0 | 0 | 1 (1.7) | NA | |
| Partial response | 49 (53.8) | 45 (52.3) | 37 (64.9) | 18 (54.5) | 31 (53.4) | |||
| Stable disease | 34 (37.4) | 34 (39.5) | 16 (28.1) | 14 (42.4) | 20 (34.5) | |||
| Progressive disease | 3 (3.3) | 2 (2.3) | 1 (1.8) | 0 | 3 (5.2) | |||
| Nonevaluable | 4 (4.4) | 4 (4.7) | 3 (5.3) | 1 (3.0) | 3 (5.2) | |||
| DOR, median, mo 95% CI | 10.6 5.8-17.7 | 12.0 5.7-18.3 | 10.6 5.6-18.3 | NA |
NA, not available.
Conclusions
T-DXd showed durable anticancer activity that was consistent across subgroups including pts with >2 prior therapies and pts with CNS met. The updated results show no new safety signals and provide further evidence supporting T-DXd as a new treatment standard in pts with previously treated HER2m NSCLC.
Clinical trial identification
NCT03505710.
Editorial acknowledgement
Under the guidance of authors, medical writing and editorial support was provided by Selene Jarrett, PhD of ApotheCom and was funded by Daiichi Sankyo.
Legal entity responsible for the study
Daiichi Sankyo and AstraZeneca.
Funding
Daiichi Sankyo and AstraZeneca.
Disclosure
B.T. Li: Non-Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Genentech, Lilly; Financial Interests, Institutional, Other, academic travel support: Jiangsu Hengrui Medicine, MORE Health ; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Bolt Biotherapeutics, Daiichi Sankyo, Genentech, Hengrui USA, Eli Lilly; Financial Interests, Personal, Royalties, intellectual property rights as a book author: Karger Publishers, Shanghai Jiao Tong University Press. 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. Y. Goto: Financial Interests, Personal, Other, Honoraria: Chugai, Taiho, Boehringer Ingelheim, Ono, Bristol Myers Squibb, Pfizer, MSD, Novartis, Merck, Thermo Fischer, Creative Therapeutical, GSK, Taiho, Novartis, Eli Lilly, Johnson & Johnson, Guardant, Nippon Kayaku, Daiichi Sankyo, BMS, Janssen, Towa, Takeda; Financial Interests, Institutional, Other, Honoraria: AstraZeneca, Kyowa Kirin; Financial Interests, Personal, Advisory Role: AstraZeneca, Chugai, Boehringer Ingelheim, Taiho, Pfizer, Novartis, Illumina, Daiichi Sankyo, Ono Pharmaceutical, Bristol Myers Squibb, MSD; Financial Interests, Personal, Advisory Role, : Guardant Health Inc.; Financial Interests, Personal, Leadership Role: Cancer Net Japan, JAMT; Financial Interests, Personal, Research Grant: IQVIA, MSD, Novartis, Mebix, CReS, Kyushu, Daiichi Sankyo, Chugai; Financial Interests, Personal, Research Grant, : Pfizer; Financial Interests, Institutional, Research Grant: IQVIA, MSD, AstraZeneca, AbbVie, Amgen, CReS Kyushu, Ono, Cmic, Daiichi Sankyo, Takeda, Chugai, Eli Lilly, Novartis, Pfizer, Mebix, BMS, Medpace, Merck BioPharma, Janssen, Preferred Network. 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. 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. J. Mazieres: Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, BMS; Financial Interests, Institutional, Research Grant: Pierre Fabre; Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Pierre Fabre, Takeda, BMS, MSD, Jiangsu Hengruii, Blueprint, Daiichi Sankyo, Novartis, Amgen. D. Uprety: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, AstraZeneca. A. Saltos: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Eli Lilly; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Novartis, Genentech, BioAtla, Memgen, Turning Point Therapeutics, AstraZeneca, Genmab; Financial Interests, Institutional, Research Grant: Mersana. 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). J. Pacheco: Financial Interests, Personal, Other, Honoraria: Sanofi; Financial Interests, Personal, Advisory Role: AstraZeneca, Gerson Lehrman Group, Hengrui Pharmaceuticals, Jazz Pharmaceuticals, Silverback Therapeutics, Novartis, Pfizer, Takeda; Financial Interests, Personal, Other, Travel Expenses: Daichii Sanyko, Checkmate Pharmaceuticals; Financial Interests, Personal, Research Grant, Honoraria: Pfizer; Financial Interests, Institutional, Other, Honoraria: Genentech, Takeda. M. Pérol: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GlaxoSmithKline; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, MBS, Boehringer Ingelheim, Takeda, Illumina, Pfizer, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Takeda, Boehringer Ingelheim. 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. K. Saxena: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. R. Shiga: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Cheng: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Q. Yan: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. 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, Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo, Janssen, AbbVie; Financial Interests, Personal, Other, Advisory/Consultancy: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Janssen, AbbVie; Financial Interests, Personal, Other, Travel expenses, including accommodations: AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer. 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. All other authors have declared no conflicts of interest.