Abstract 11P
Background
Tolerable therapies are needed for previously treated pts with advanced EGFRm NSCLC. The ph 2 HERTHENA-Lung01 trial (NCT04619004) showed meaningful efficacy and a manageable safety profile. To extend these safety observations, we present data with an additional 6 mo of follow-up.
Methods
Pts (N=225) previously treated with EGFR TKI and platinum-based chemotherapy received HER3-DXd 5.6 mg/kg IV Q3W.
Results
Median treatment (TX) duration was 5.5 (range, 0.7-23.7) mo. 224 pts (99.6%) had any-grade (G) TEAEs; 147 (65.3%) had G ≥3. Most common any-G TEAEs were nausea (66.2%), thrombocytopenia (43.6%), and decreased appetite (42.2%); most common G ≥3 were thrombocytopenia (20.9%), neutropenia (19.1%), and anemia (15.1%). 88.9% of pts had a GI TEAE; 8% had a G ≥3 event. Incidence of GI TEAEs generally decreased over the course of TX. 2 pts (0.9%) experienced G ≥3 bleeding unrelated to TX within ±14 d of G ≥3 decreased platelet count. 2 pts (0.9%) experienced G ≥3 infections unrelated to TX within ±14 d of G ≥3 decreased neutrophil count. Febrile neutropenia occurred in 7 pts (3.1%; all G ≥3). G-CSF was used to manage neutropenia in 23 pts (10.2%). 14 pts (6.2%) had centrally adjudicated TX-related interstitial lung disease (G 1/2, n=9; G 3, n=4; G 5, n=1); 2 events occurred in the 6-mo follow-up. Median time to onset and duration were 70.5 (range, 9-474) and 40 (range, 6-207) d. 4 pts had TX-related TEAEs associated with death (pneumonitis, GI perforation, pneumonia, respiratory failure [n=1 each]). TEAEs associated with dose interruption occurred in 41.3% of pts, dose reduction in 22.2%, and discontinuation in 8.4%. Hematologic AEs occurred early in TX, were transient, and managed by dose modifications and supportive care. No pts discontinued TX due to thrombocytopenia; 20 (8.9%) received platelet transfusions. Anemia was associated with TX discontinuation in 1 pt (0.4%); 28 (12.4%) received RBC transfusions.
Conclusions
HER3-DXd demonstrated a manageable safety profile, consistent with previous reports. Hematologic and GI TEAEs typically occurred in early TX cycles. No additional safety signals were observed.
Clinical trial identification
NCT04619004.
Editorial acknowledgement
Medical editorial assistance was provided by Allison Lytle, PhD, CMPP (Nucleus Global).
Legal entity responsible for the study
Daiichi Sankyo, Inc.
Funding
Daiichi Sankyo, Inc.
Disclosure
H. Hayashi: Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical, Bristol Myers Squibb Japan, Lilly, Boehringer Ingelheim, AstraZeneca Japan, Chugai Pharma, Pfizer, MSD, Novartis, Merck Serono, Amgen, Daiichi Sankyo/UCB Japan, Guardant Health, Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo/UCB Japan, Janssen; Financial Interests, Personal, Research Grant: Ono Pharmaceutical, Boehringer Ingelheim, AstraZeneca; Financial Interests, Institutional, Research Grant: AbbVie, AC Medical, Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Lilly Japan, EPS Associates Co., Ltd, GSK, Japan Clinical Research Operations, Kyowa Hakko Kirin, Merck Serono, Novartis, Otsuka, PAREXEL, Pfizer, PPD-SNBL, Quintiles Inc, Taiho Pharmaceutical, Takeda, Yakult Honsha, Chugai Pharma, Sysmex; Financial Interests, Personal, Royalties: Sysmex. 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, Personal, Other, Travel Grant: Daiichi Sankyo; 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; Non-Financial Interests, Personal, Member of Board of Directors: Cancer Net Japan, JAMT. H.A. Yu: Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi Sankyo, Blueprint Medicines, Janssen, C4 Therapeutics, Cullinan Oncology, Black Diamond Therapeutics, Taiho Oncology, AbbVie; Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas Pharma, Lilly, Novartis, Pfizer, Daiichi Sankyo, Cullinan Oncology, Janssen Oncology, Erasca, Inc, Blueprint Medicines, Black Diamond Therapeutics; Financial Interests, Personal, Other: Astellas Pharma. 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, Duality Biologics; Financial Interests, Personal, Advisory Board, Consulting fees for advice on diagnostic development: Biocartis; Financial Interests, Personal, Advisory Board, Consulting fee for advice on drug development: Merus, Frontier Medicines; Financial Interests, Personal, Advisory Board, Consulting fees for advice on drug development.: Hongyun Biotechnology; 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. J.C. Yang: Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim, Roche, MSD, AstraZeneca, Novartis, Bristol Myers Squibb, Ono Pharmaceutical, Takeda, Lilly, Pfizer; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Novartis, AstraZeneca, Clovis Oncology, Lilly, MSD Oncology, Merck Serono, Celgene, Bayer, Pfizer, Ono Pharmaceutical, Bristol Myers Squibb, Yuhan, Hansoh, Blueprint Medicines, Daiichi Sankyo, G1 Therapeutics, AbbVie, Takeda, Amgen, Incyte; Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim, Merck Serono, Janssen, GSK, Amgen, Takeda, Daiichi Sankyo, AstraZeneca, Novartis, MSD Oncology; Financial Interests, Personal, Other, Travel, Accomodations, Expenses: Pfizer. M. Reck: Financial Interests, Personal, Advisory Role: Lilly, MSD Oncology, Merck Serono, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, Roche/Genentech, AbbVie, Amgen, Mirati Therapeutics, Samsung Bioepis, Sanofi/Regeneron, Daiichi Sankyo Europe GmbH; Financial Interests, Personal, Speaker’s Bureau: Roche/Genentech, Lilly, MSD Oncology, Merck Serono, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Pfizer, Novartis, Amgen, Mirati Therapeutics, Sanofi/Aventis. K. Yoh: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Lilly, Boehringer Ingelheim, Amgen, Takeda, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Lilly, Daiichi Sankyo, AbbVie, Taiho, MSD, Takeda, Amgen, Boehringer Ingelheim, Chugai. S. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune, Roche, Merck, Pfizer, Lilly, BMS/Ono, Takeda, Janssen, IMBdx; Financial Interests, Personal, Invited Speaker: AstraZeneca/MedImmune, Roche, Merck, Lilly, Amgen; Financial Interests, Institutional, Research Grant: Merck, AstraZeneca, Lunit. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daiichi Sankyo, 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, Personal, Member of Board of Directors, Board member: Stab Therapeutics; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-Cilag international NV, NOoartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Member: AACR, ASCO, ESMO; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, President. ASEICA(Spanish Association of Cancer Research ): ASEICA; Financial Interests, Personal, Other, Foundation president: ONCOSUR; Financial Interests, Personal, Other, member: Small Lung Cancer Group. B. Besse: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Beigene, Blueprint Medicine, Cergentis, Chugai pharmaceutical, Daiichi Sankyo, F. Hoffmann-La Roche, Inivata, Pfizer, PharmaMar, Sanofi Aventis, Springer Healthcare Ltd, 4D Pharma; Financial Interests, Institutional, Expert Testimony: AbbVie, Da voltera, Eli Lilly, Ellipse pharma Ltd, F-Star, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Socar research, Taiho oncology, Turning Point Therapeutics; Financial Interests, Institutional, Invited Speaker: Genzyme Corporation, Hedera Dx, Medscape, MSD, AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi Sankyo, GSK, Janssen, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Turning Point Therapeutics, Genmab, Taiho, Nuvalent, Enliven, Prelude therapeutics; Financial Interests, Institutional, Funding: Cristal Therapeutics. P. Bironzo: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, MSD Oncology, Roche, Takeda, Novartis, Sanofi; Financial Interests, Personal, Advisory Role: Roche, Janssen Oncology, Pierre Fabre, Amgen, Seagen, Regeneron; Financial Interests, Institutional, Research Grant: Roche, Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen, Daiichi Sankyo/Arqule. D. Kim: Financial Interests, Personal, Invited Speaker: Korean Cancer Association, Korean Society of Medical Oncology, Korean Association for Lung Cancer, Japan Cancer Association; Financial Interests, Personal, Other, Scientific Advisor: Health Insurance Review & Assessment Service, Korea; Financial Interests, Personal, Invited Speaker, Medical writing assistance: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Chong Keun Dang, Daiichi Sankyo, GSK, Pfizer, MSD, Merck, Novartis, Roche, Takeda, Yuhan; Financial Interests, Institutional, Invited Speaker, Clinical Trial Funding: Alpha Biopharma, Amgen, AstraZeneca/MedImmune, Boehringer Ingelheim, Daiichi Sankyo, Hanmi, Janssen, Merus, MIrati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan, Chong Keun Dang, Bridge BioTherapeutics, GSK; Financial Interests, Institutional, Research Grant, Laboratory research funding to my institution: InnoN; Non-Financial Interests, Personal, Advisory Role: Amgen, BMS / Ono Pharmaceuticals, Daiichi Sankyo, Janssen, GSK, Pfizer, AstraZeneca, SK Biopharm, Takeda, Yuhan; Non-Financial Interests, Personal, Member of Board of Directors: Korean Society of Medical Oncology, Korean Association for Lung Cancer, Asian Thoracic Oncology Research Group; Non-Financial Interests, Personal, Advisory Role, Member of Scientific Advisory Board: Novelty Nobility; Other, Personal, Other, Clinical trial research funding to my institution: Asian Thoracic Oncology Research Group. Z. Piotrowska: Financial Interests, Personal, Invited Speaker, Participated in a Janssen-sponsored educational program: Janssen; Financial Interests, Personal, Advisory Board: Janssen, Takeda, Cullinan, C4 Therapeutics, Taiho, Sanofi; Financial Interests, Personal, Invited Speaker, Participated as an invited speaker in an internal education program at Daiichi Sankyo: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Participated in a (non-promotional) Eli Lilly sponsored medical education event about biomarker testing in NSCLC: Eli Lilly; Financial Interests, Institutional, Research Grant, Institutional research funding for clinical trial: Novartis, Takeda, Spectrum, AstraZeneca, Tesaro/GSK, Cullinan, Daiichi Sankyo, AbbVie, Janssen, Blueprint; Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator: Cullinan, AstraZeneca. M.L. Johnson: Financial Interests, Institutional, Other, Consulting: AbbVie, Amgen, Arcus Biosciences, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Daiichi Sankyo, EcoR1, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Ideaya Biosciences, Immunocore, iTeos, Janssen, Jazz Pharmaceuticals, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Oncorus, Pyramid Biosciences, Regeneron Pharmaceuticals, Revolution Medicines, Sanofi-Aventis, SeaGen, Synthekine, Takeda Pharmaceuticals, Turning Point Therapeutics, VBL Therapeutics; Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Checkpoint Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchinson MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Kartos Therapeutics, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL Therapeutics, Y-mAbs Therapeutics. A. Sporchia: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo Europe GmbH, MorphoSys. K.H. Sullivan: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc. Q. Dong: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. P. Shrestha: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Daiichi Sankyo. J. Shah: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Personal, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí.