Abstract 1195TiP
Background
Standard therapies for patients (pts) with epidermal growth factor receptor–mutated (EGFRm) non-small cell lung cancer (NSCLC) that has progressed after treatment with third-generation (3rd-gen) EGFR tyrosine kinase inhibitors (TKIs) offer only a limited benefit. Human epidermal growth factor receptor 3 (HER3) is often expressed in primary NSCLC tumors, and HER3 expression is commonly observed in patients with EGFR mutations. HER3-DXd is a novel antibody-drug conjugate composed of a human anti-HER3 monoclonal antibody (patritumab) linked to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. HER3-DXd demonstrated efficacy and safety in a phase I study in pts with EGFRm NSCLC that progressed following an EGFR TKI and platinum-based chemotherapy (PBC) (U31402-A-U102; NCT03260491).
Trial design
HERTHENA-Lung02 (NCT05338970) is a global, open-label, randomized, phase III trial evaluating the efficacy and safety of HER3-DXd vs PBC in pts (≈560) with metastatic or locally advanced nonsquamous NSCLC with an EGFR-activating mutation (exon 19 deletion or L858R) who have received 1 or 2 lines of EGFR TKI treatment including a 3rd-gen EGFR TKI and had disease progression following treatment with a 3rd-gen EGFR TKI. Pts are randomized 1:1 to receive either HER3-DXd 5.6 mg/kg every 3 weeks or 4 cycles of PBC containing pemetrexed (can be continued as maintenance) with cisplatin or carboplatin. Pts are stratified by prior 3rd-gen EGFR TKI treatment (osimertinib vs other), line of prior 3rd-gen EGFR TKI use (first vs second line), region (Asia vs rest of world), and presence of stable brain metastases (yes vs no). The primary endpoint is progression-free survival (PFS) per blinded independent central review (BICR per RECIST v1.1). The key secondary endpoint is overall survival. Other secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, clinical benefit rate, disease control rate, time to response (all per BICR per RECIST v1.1), safety, and patient-reported outcomes. Enrollment into the trial is starting in Q2 2022.
Clinical trial identification
NCT05338970.
Editorial acknowledgement
Writing and editorial assistance was provided by Martin Haschak, PhD, of Scimentum, a Nucleus Holding Ltd company, and funded by Daiichi Sankyo.
Legal entity responsible for the study
Daiichi Sankyo.
Funding
Daiichi Sankyo.
Disclosure
T.S.K. Mok: Financial Interests, Personal, Invited Speaker: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Fishawack Facilitate, InMed Medical Communication, Lunit USA, Inc., Merck Serono, MSD, Roche, MD Health, Medscape/WebMD, PeerVoice, Permanyer SL, Prime Oncology, Research to Practice, Touch Medical Media, Sanofi-Aventis, Takeda, Per, AstraZeneca, Hutchison Chi-Med; Financial Interests, Personal, Advisory Board: AbbVie, Acea Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Blueprint Medicines, Berry Oncology, CStone Pharma, Daiichi Sankyo, Fishawack Facilitate, Eisai, Gritstone Oncology, Guardant Health, G1 Therapeutics, Hengrui, Ignyta, IQVIA, Incyte Corporation, Inivata, Janssen, Loxo Oncology, Qiming Dev., Lunit USA, Inc., Merck Serono, MSD, Roche, Mirati Therapeutics, MoreHealth, Novartis, OrigiMed, Puma Tech., Sanofi-Aventis, Takeda, Virtus Medical, Yuhan, Curio Science; Financial Interests, Personal, Stocks/Shares: Sanomics Ltd., Hutchison Chi-Med, Biolidics Ltd., Loxo Oncology, OrigiMed Co., Virtus Medical Group, Lunit USA, Inc., Aurora Tele-Oncology; Financial Interests, Institutional, Funding, For clinical trials performed at CUHK: AstraZeneca, BMS, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology; Non-Financial Interests, Advisory Role: geneDecode, AstraZeneca; Non-Financial Interests, Other, Invited Speaker: AstraZeneca; Non-Financial Interests, Invited Speaker: Aurora Tele-Oncology, Lunit USA, Inc., Sanomics Ltd.; Non-Financial Interests, Leadership Role: American Society of Clinical Oncology (ASCO), Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Chinese Society of Clinical Oncology (CSCO), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), St. Stephen’s College & Prep. School (Hong Kong); Non-Financial Interests, Leadership Role, Term ended on 30 April 2019: International Association for the Study of Lung Cancer (IASLC). Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda; Financial Interests, Invited Speaker: AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, Yunhan, Eli Lilly; Non-Financial Interests, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO). M. Nishio: Financial Interests, Personal and Institutional, Advisory Role: Ono Pharmaceutical, Chungai Pharmaceutical, Taiho Pharmaceutical, Bristol-Myers Squibb Japan, Daiichi Sankyo, AstraZeneca, MSD, AbbVie, Takeda, Teijin Pharma; Financial Interests, Personal and Institutional, Other, Honoraria: Pfizer, Bristol-Myer Squibb Japan, Ono Pharmaceutical, Chugai Pharmaceutical, Taihi Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Lilly, Nippon Kayaku, Takeda, Merck, Janssen; Financial Interests, Personal and Institutional, Research Grant: Novartis, Ono Pharmaceutical, Chugai Pharma, Bristol Myers Squibb, Taiho Pharmaceutical, Pfizer, AstraZeneca, Lilly, MSD, Merck, Takeda. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Lilly, MSD, Novartis, Merck, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Mirati, Pfizer, Sanofi, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, MSD, Roche. E. Wu: Financial Interests, Personal and Institutional, Stocks/Shares: Daiichi Sankyo, Daiichi Sankyo ; Non-Financial Interests, Personal and Institutional, Speaker’s Bureau: Daiichi Sankyo. D.W. Sternberg: Financial Interests, Personal and Institutional, Stocks/Shares: Daiichi Sankyo. S. Esker: Financial Interests, Personal and Institutional, Stocks/Shares: Daiichi Sankyo. H.A. Yu: Financial Interests, Personal and Institutional, Research Grant: Daiichi Sankyo, AstraZeneca, Bluprint, Novartis, Pfizer, Cullinan, ERASCA; Financial Interests, Personal and Institutional, Advisory Role: Daiichi Sankyo, AstraZeneca, Cullinan, C4 Therapeutics, Blueprint, Janssen, Black Diamond.