1314MO - 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: 1314MO

Primary results (N=137)

^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

Medical writing support was provided by Kristie Garza, PhD, of SciMentum, Inc, a Nucleus Holdings Ltd company, and was funded by Daiichi Sankyo, Inc. Editorial support was provided in accordance with good publication practice guidelines.

Legal entity responsible for the study

Daiichi Sankyo, Inc.

Funding

Daiichi Sankyo, Inc.

Disclosure

L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daiichi, 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, Coordinating PI: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme Corp, BMS, Janssen-Cilag International NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: 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): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. M. Ahn: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, Yuhan, Amgen, Roche, Pfizer, Alpha Pharmaceuticals, Takeda, Voronoi, Eutilex, Daiichi Sankyo; Financial Interests, Personal and Institutional, Advisory Role: Arcus. A.E. Lisberg: Financial Interests, Personal, Full or part-time Employment, Immediate Family Member: Boston Scientific; Financial Interests, Personal, Stocks or ownership, Immediate Family Member: Boston Scientific; Financial Interests, Personal, Other, Honoraria; Consulting or advisory role: AstraZeneca, Bristol Myers Squibb, Leica Biosystems, Jazz Pharmaceuticals, Novocure, Pfizer, Eli Lilly, Novartis, Regeneron, Janssen oncology , Sanofi group of companies; Financial Interests, Personal, Other, HoHonoraria; Consulting or advisory rolenoraria: MorphoSys; Financial Interests, Institutional, Research Funding: Daiichi Sankyo, Calithera Biosciences, AstraZeneca, Dracen Pharmaceuticals , WindMIL, eFFECTOR Therapeutics. S. Kitazono: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Ono Pharmaceutical Co, Chugai Pharmaceutical Co., Ltd. B.C. Cho: Financial Interests, Personal, Stocks or ownership: TheraCanVac Inc, Gencurix Inc, BridgeBio therapeutics, Kanaph Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J Ints Bio; Financial Interests, Personal and Institutional, 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. E. Shum: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Blueprint Medicines; Financial Interests, Institutional, Research Funding: Delfi Diagnostics. E. Pons-Tostivint: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, BMS, Sanofi; 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 Fisher; 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, 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, Institutional, Research Funding: AbbVie, Agios, Corvus, Daiichi Sankyo, Erasca, Lilly, Mirati, Novartis, Turning Point; Financial Interests, Personal, Advisory Board, Consulting fees: AbbVie, Daiichi Sankyo, EMD Serono, Lilly, Novartis, Regeneron, Sanofi. P. Baas: Financial Interests, Institutional, Speaker, Consultant, Advisor: BMS; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Role: Amheart, BeiGene; Financial Interests, Institutional, Research Funding: AstraZeneca. M. Pérol: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GSK, Eisai, 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, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. W. Su: Financial Interests, Personal, Other, Consulting or advisory role: Merck, MSD, Bayer, Roche; Financial Interests, Personal, Other, Honoraria; Consulting or advisory role: Lilly. H. Zebger-Gong: Financial Interests, Personal and Institutional, Full or part-time Employment, Full-time employment: Daiichi Sankyo; Financial Interests, Personal and Institutional, Stocks or ownership, Stock options: Daiichi Sankyo; Financial Interests, Personal, Stocks or ownership, Stocks: Bayer. C. Liu: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Sands: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Sanofi, Takeda, Jazz Pharmaceuticals, Pharma Mar, Sanofi, Merck, Guardant, Medtronic, Amgen; Financial Interests, Personal, Advisory Board: Curadev; Financial Interests, Institutional, Local PI: Genentech, Merck, Pharma Mar, Legend, Amgen, Daiichi Sankyo, Lilly; Financial Interests, Institutional, Member: Phanes. All other authors have declared no conflicts of interest.