Abstract 552P
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
Endpoint | Pts (N=66) |
Efficacy a | |
ORR, n (%) [95% CI] | 28 (42.4) [30.3–55.2] |
Complete response | 2 (3.0) |
Partial response | 26 (39.4) |
ORR in EGFRm pts (n=47)) | 23 (48.9) [34.1–63.9] |
mDORb, mo [95% CI] | 4.4 [4.0–14.0] |
DCR, n (%) [95% CI] | 53 (80.3) [68.7–89.1] |
mPFS, mo [95% CI] | 5.4 [4.2–6.9] |
Safety, n (%) | |
Any TEAE | 66 (100) |
Grade ≥3 TEAEs | 24 (36.4) |
Serious TEAEs | 10 (15.2) |
TEAEs associated with: | |
Dose reduction | 11 (16.7) |
Drug discontinuation | 5 (7.6) |
Death | 1 (1.5)c |
Adjudicated drug-related ILD | |
Grade 1/2 | 2 (3.0) |
Grade ≥3 | 0 |
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.
Resources from the same session
506P - Intrathoracic progression is still the most dominant failure pattern after first-line chemo-immunotherapy in extensive-stage small-cell lung cancer: Implications for thoracic radiotherapy
Presenter: Byoung Hyuck Kim
Session: Poster Display
Resources:
Abstract
519P - Final results and subgroup analysis of ORIENTAL: A phase IIIB study of durvalumab plus platinum-etoposide in first-line treatment of Chinese patients with extensive-stage small-cell lung cancer (ES-SCLC)
Presenter: Ying Cheng
Session: Poster Display
Resources:
Abstract
520P - Role of atezolizumab in controlling CNS progression in ES-SCLC
Presenter: Yoon Namgung
Session: Poster Display
Resources:
Abstract
521P - Camrelizumab combined with chemotherapy and apatinib as first-line therapy for extensive-stage small cell lung cancer: A phase II, single-arm, exploratory research
Presenter: Yanbin Zhao
Session: Poster Display
Resources:
Abstract
522P - Durvalumab plus etoposide and carboplatin for extensive-stage small cell lung cancer with mild idiopathic interstitial pneumonia
Presenter: Ichiro Nakachi
Session: Poster Display
Resources:
Abstract
523P - Camrelizumab plus apatinib as maintenance treatment in patients with extensive-stage small cell lung cancer who were responding or stable after standard first-line chemotherapy (CAMERA): Results from a single-arm, phase II trial
Presenter: Qi Wang
Session: Poster Display
Resources:
Abstract
524P - Treatment pattern and overall survival by lines of therapy among patients with advanced small cell lung cancer in Taiwan
Presenter: Kelly Huang
Session: Poster Display
Resources:
Abstract
525P - Development of diagnostic prediction score for malignant pleural effusion in lung cancer: MPE-Lung score
Presenter: Chaichana Chantharakhit
Session: Poster Display
Resources:
Abstract
526P - Burden and trends of tracheal, bronchus, and lung (TBL) cancer in Southeast Asia, East Asia, and Oceania from 1990-2019, and its projection of deaths to 2040: A benchmarking analysis
Presenter: Monika Chhayani
Session: Poster Display
Resources:
Abstract
527P - Efficacy of intraventricular chemotherapy with pemetrexed for leptomeningeal metastasis from lung adenocarcinoma: A retrospective study
Presenter: Fang Cun
Session: Poster Display
Resources:
Abstract