552P - TROPION-Lung05: Datopotamab deruxtecan (Dato-DXd) in Asian patients (pts) with previously treated non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGAs)

Background

Dato-DXd is an antibody-drug conjugate composed of a TROP2-directed monoclonal antibody covalently linked to a highly potent cytotoxic topoisomerase I inhibitor payload via a plasma stable, tumor-selective, cleavable linker. We report results from pts enrolled in Asia as part of the global phase 2 TROPION-Lung05 trial (NCT04484142) evaluating Dato-DXd in pts with advanced/metastatic (a/m) NSCLC with AGAs progressing on or after ≥1 AGA-specific therapy and 1 PBC.

Methods

Dato-DXd 6 mg/kg was given every 21 days to pts with a/m NSCLC, ECOG status 0/1, and ≥1 documented AGA in EGFR (EGFRm), ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET. Primary endpoint was confirmed objective response rate (ORR) by blinded independent central review (BICR). Secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS) by BICR, and safety.

Results

Of 137 pts, 66 were from Asia and received ≥1 dose; 68.2% had ≥3 prior lines of therapy for a/m NSCLC; 71.2% had EGFRm. As of 14 Dec 2022, 83.3% discontinued therapy, 69.7% had disease progression, and 42.4% died. Median (m) study and treatment duration were 15.7 and 5.7 months (mo). ORR was 42.4% (48.9% in EGFRm pts); mDOR by BICR was 4.4 mo, DCR was 80.3%, and mPFS was 5.4 mo (Table). The most common grade ≥3 TEAEs were amylase increased (10.6%), stomatitis (6.1%), and anemia (4.5%). No grade ≥3 adjudicated drug-related interstitial lung disease (ILD) was reported (Table). Table: 552P

Primary results

^aBy BICR per RECIST v1.1. ^bmDOR 7.0 mo [95% CI: 5.1–13.6] by investigator. ^cOne case reported as dyspnea associated with disease progression, unrelated to study drug per investigator.

Conclusions

Dato-DXd showed encouraging antitumor activity, with clinically meaningful responses in a heavily pretreated Asian pt subpopulation. The safety profile was manageable and consistent with prior Dato-DXd safety observations. The results are consistent with the overall TROPION-Lung05 study population and supported inclusion of Asian pts with AGAs in the phase 3 TROPION-Lung01 study (NCT04656652).

Clinical trial identification

NCT04656652.

Editorial acknowledgement

Medical writing support was provided by Matty Stone, MRes, and editorial support was provided by Jess Galbraith, BSc, both of Prime Global.

Legal entity responsible for the study

Daiichi Sankyo.

Funding

Daiichi Sankyo.

Disclosure

M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Yuhan, Amgen, Alpha Pharmaceutical, BMS, Roche, Daiichi Sankyo, Merck, Pfizer. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc.; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Institutional, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, Abbvie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine., Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Other, Personal, Other, Founder: DAAN Biotherapeutics; Employment: Yonsei University Health System; Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Medical Onoclogy, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer. 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, Local PI: Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Preferred Network; Financial Interests, Personal and Institutional, Coordinating PI: Chugai, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Preferred Network; Financial Interests, Institutional, Coordinating PI: Guardant Health; Non-Financial Interests, Personal, Member of Board of Directors: Cancer Net Japan, JAMT. K. Yoh: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi sankyo, Lilly, Boehringer Ingelheim, Amgen, Takeda; Financial Interests, Institutional, Local PI: AstraZeneca, Lilly, Daiichi sankyo, AbbVie, Taiho, MSD, Takeda, Amgen, Boehringer Ingelheim, Chugai; Financial Interests, Personal, Steering Committee Member: AstraZeneca. J. Shimizu: Financial Interests, Personal, Speaker, Consultant, Advisor: Daiichi Sankyo; Financial Interests, Institutional, Local PI: Daiichi Sankyo. S. Oizumi: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Institutional, Research Funding: Amgen, Bristol Myers Squibb, Chugai, Daiichi Sankyo, MSD, AstraZeneca. J.C-H. Yang: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Takeda, Yuhan Pharmaceuticals, JNJ, Gilead, GSK, ArriVent Biopharma, Dizal Pharma, Hansoh Pharma. H. Hayashi: Financial Interests, Personal, Invited Speaker: Guardant Health Japan Corp., Ono Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd., AstraZeneca K.K., Eli Lilly Japan K.K., Merck Biopharma Co., Ltd., 3H Clinical Trial Inc., Novartis Pharma K.K., Amgen Inc., Sysmex Corporation; Financial Interests, Personal and Institutional, Invited Speaker: Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Bristol Myers Squibb Company, Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal and Institutional, Research Funding: Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal and Institutional, Research Grant: MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Bristol Myers Squibb Company; Financial Interests, Institutional, Research Grant: IQVIA Services JAPAN K.K., syneos health clinical K.K., EPS Corporation., Nippon Kayaku Co., Ltd., Amgen Inc., Taiho Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., CMIC CO., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Kobayashi Pharmaceutical Co., Ltd., EP-CRSU CO., LTD., Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., GSK K.K., Sanofi K.K., SRL Medisearch Inc., PRA Health Sciences Inc., Astellas Pharma Inc., Ascent Development Services, Eisai Inc., Bayer Yakuhin; Financial Interests, Institutional, Research Funding: Eisai Co., Ltd. H. Zebger-Gong: Financial Interests, Institutional, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Institutional, Stocks/Shares, Stock options as an employee: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares, Stocks during previous period as a former employee: Bayer. K. Sugiura: Financial Interests, Personal and Institutional, Stocks/Shares, Employee stock: Daiichi Sankyo. All other authors have declared no conflicts of interest.