518MO - TROPION-Lung05: Datopotamab deruxtecan (Dato-DXd) in previously treated non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGAs)

Background

Once targeted therapies and platinum-based chemotherapy (PBC) become ineffective in patients (pts) with advanced/metastatic (a/m) NSCLC with AGAs, few treatments with limited benefit are available. Dato-DXd is an antibody-drug conjugate composed of a TROP2 directed monoclonal antibody covalently linked to a highly potent cytotoxic payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. We report primary results from the global, open-label, phase 2 TROPION-Lung05 trial (NCT04484142) evaluating Dato-DXd in pts with a/m NSCLC with AGAs progressing on or after ≥1 AGA-specific therapy and PBC.

Methods

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

Results

A total of 137 pts received ≥1 dose and had a median age of 61.0 y; 71.5% had ≥3 prior lines of therapy for a/m NSCLC; 56.9% had EGFR mutations. As of 14 Dec 2022, 85.4% discontinued therapy, 63.5% had disease progression, and 49.6% died. Median pt duration on study was 15.2 months (mo); cORR was 35.8%, DCR, 78.8%, and median DOR, 7.0 mo; similar response was seen in pts with EGFR mutations (Table). The most common grade ≥3 TEAEs were stomatitis (9.5%), anemia (5.8%), and increased amylase (5.8%). Table: 518MO

Primary results (N=137)

ILD, interstitial lung disease.^aBy BICR. ^bTwo cases associated with disease progression, unrelated to study drug by investigator. ^cOne grade 3 reported event, with death due to disease progression by investigator and adjudicated grade 5 ILD.

Conclusions

Dato-DXd showed encouraging antitumor activity, with a clinically meaningful and durable response, in heavily pretreated pts with NSCLC with AGAs. The safety profile was manageable and consistent with prior safety observed with Dato-DXd. These data support inclusion of pts with AGAs in the TROPION-Lung01 study (NCT04656652).

Clinical trial identification

NCT04484142.

Editorial acknowledgement

Daiichi Sankyo.

Legal entity responsible for the study

Daiichi Sankyo.

Funding

Daiichi Sankyo.

Disclosure

S. Kitazono: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Ono Pharmaceutical Co, Chugai Pharmaceutical CO., LTD. L. Paz-Ares: Financial Interests, Personal, Other, Consulting role: Lilly, MSD, Roche, Pharmamar, Merck KGaA (Darmstadt, Germany), AstraZeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, Daichii Sankyo; Financial Interests, Personal, Other, Payment for honoraria for lectures, presentations, speakers bureaus, educational events: AstraZeneca, Janssen, Merck, Mirati; Financial Interests, Personal, Other, Member of the board of directors: Altum sequencing, Stab Therapeutics. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Yuhan, Amgen, ALPHA Pharmaceutical, BMS, Roche, Daiichi Sankyo, Merck, Pfizer. A.E. Lisberg: Financial Interests, Personal, Other, Consulting, Lectures or Advisory Role at Bayer, Daiichi Sankyo, Inc., AstraZeneca, Novocure, Eli Lilly, Oncocyte, Novartis, Regeneron, Janssen Oncology, MorphoSys, Sanofi group of companies, Molecular Axiom, Amgen, IQVIA, G1 Therapeutics, Bristol-Myers Squibb, Leica Biosystems, Jazz Pharmaceuticals, Pfizer, Platformq, HMP Global, MJH Associates, Med Learning, Clinical Care Options, Physicians Educational Resources, Curio Sciences, Vaniam Group, Medscape, Projects in Knowledge, Aptitude Health, MOASC, SITC; Grant/Research Support from Daiichi Sankyo, Inc., Calithera, AstraZeneca, Dracen, WindMIL, Duality Biologics, Effector Therapeutics, LUNGevity and NIH/NCI; Funding for the current study by Daiichi Sankyo Inc. and AstraZeneca. 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. E. Shum: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Boehringer-Ingleheim, Janssen, Regeneron; Financial Interests, Institutional, Funding: Delfi Diagnostics. E. Pons-Tostivint: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, BMS, Sanofi; No Financial Interests, Institutional, Local PI: AstraZeneca, BMS, Daiichi Sankyo, Sanofi, PDC line, Takeda, Amgen. 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: Prefered 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. R. Heist: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Novartis, EMD Serono, Lilly, AstraZeneca, Regeneron, Sanofi; Financial Interests, Personal, Writing Engagement: Chugai Roche; Financial Interests, Personal, Other, review of cancer histories: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, consulting honoraria: AbbVie; Financial Interests, Personal, Other, Consulting: Claim Therapeutics; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Novartis, AbbVie, Roche, Incyte, Mirati, Agios, Corvus, Turning Point, Lilly, Exelixis; Financial Interests, Institutional, Local PI, clinical trial funding to institution, not to self: Erasca, Mythic; Non-Financial Interests, Personal, Member: IASLC, ASCO, AACR. P. Baas: Financial Interests, Institutional, Advisory Board: BMS, MSD; Financial interests, Institutional, advisory role: AmHeart, AstraZeneca, Takeda; Financial Interests, Institutional, Research Grant: MSD, BMS. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Personal, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Personal, Principal Investigator: AbbVie, Sanofi, Janssen. M. Pérol: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, TAKEDA, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GSK, Esai, Ipsen; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, BMS, Boehringer Ingelheim, Takeda, Illumina, Pfizer, Medscape; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Takeda, Boehringer Ingelheim; Financial Interests, Personal, Steering Committee Member: Roche; Financial Interests, Personal, Other, DMSB: Roche. 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, Local PI, 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 Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. H. Zebger-Gong: Financial Interests, Institutional, Full or part-time Employment, full-time employee: 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. J. Sands: Financial Interests, Personal, Speaker, Consultant, Advisor: Arcus, AstraZeneca, Curadev; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Daiichi Sankyo, Pharma Mar, Amgen, Boehringer Ingelheim; Financial Interests, Personal, Local PI: AstraZeneca; Financial Interests, Personal and Institutional, local PI: Daiichi Sankyo, PharmaMar, Amgen, Boehringer Ingelheim; Non-financial interests, institutional, local PI: Phanes, Legend, Genentech. All other authors have declared no conflicts of interest.