LBA7 - Efficacy and safety of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously-treated EGFR-mutated advanced non-small cell lung cancer (NSCLC): A pooled analysis of TROPION-Lung01 and TROPION-Lung05

Background

Targeted therapies have improved outcomes for pts with EGFR-mutated (EGFRm) metastatic NSCLC; however, most will eventually progress. Dato-DXd, a TROP2-directed antibody-drug conjugate, has shown a favorable benefit/risk profile in pts with NSCLC and actionable genomic alterations. Here we report a pooled analysis of pts with EGFRm NSCLC from the phase 2 TROPION-Lung05 (NCT04484142) and phase 3 TROPION-Lung01 (NCT04656652) studies treated with Dato-DXd following progression on prior targeted therapies and chemotherapy.

Methods

Pts with advanced or metastatic NSCLC and documented EGFR mutations, previously treated with targeted therapy and platinum-based chemotherapy, who received Dato-DXd monotherapy (6 mg/kg Q3W) across both studies were included. Efficacy and safety outcomes were assessed.

Results

Pts with EGFRm disease (N=117; TROPION-Lung05, n=78; TROPION-Lung01, n=39) were pooled. Median age was 63 years (range, 36–81); 73 pts (62%) were female. Pts had a median of three prior lines of therapy in the locally advanced or metastatic setting (range, 1–5). The confirmed objective response rate (cORR) by blinded independent central review was 43%, median duration of response (mDOR) was 7.0 months (mo), and disease control rate (DCR) was 86%. Survival outcomes within each trial are shown in the table. The most frequent adverse event of special interest was stomatitis/oral mucositis (any grade, 81 pts [69%]; grade ≥3, 11 pts [9%]). No grade 4 or 5 adjudicated drug-related interstitial lung disease events were reported. No study drug-related deaths were seen. Table: LBA7

^aCR+PR; ^bCR+PR+SD or non-CR/non-PD; ^cPFS/OS time-to-event outcomes presented independently for the single-arm TROPION-Lung05 and randomized TROPION-Lung01 studies. CI, confidence interval; CR, complete response; mOS, median overall survival; mPFS, median progression-free survival; NE, not evaluable; PR, partial response; SD, stable disease.

Conclusions

Dato-DXd elicited encouraging efficacy and manageable safety in previously treated pts with EGFRm NSCLC. These findings suggest a potential clinical role for Dato-DXd in this population with high unmet need.

Clinical trial identification

TROPION-Lung01: NCT04656652, first posted December 7, 2020; TROPION-Lung05: NCT04484142, first posted July 23, 2020.

Editorial acknowledgement

Medical writing support for this late-breaker shell abstract was provided by Nicole Draghi of Daiichi Sankyo.

Legal entity responsible for the study

Daiichi Sankyo.

Funding

This study is sponsored by Daiichi Sankyo. In July 2020, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for datopotamab deruxtecan (Dato-DXd; DS-1062).

Disclosure

M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, MSD, Yuhan, Amgen, Alpha Pharmaceutical, Janssen, Bristol Myers Squibb, Roche, Daiichi Sankyo, Merck, BORONOI. J. Sands: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Gilead, Lilly, Sanofi, AbbVie, G1 Therapeutics, Pharma Mar; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Research Grant: Amgen, Harpoon; Non-Financial Interests, Personal, Member of Board of Directors, President of medical society working to advance lung cancer screening: Rescue Lung Society. A.E. Lisberg: Financial Interests, Personal, Other, Consulting: Bayer, IQVIA, Leica Biosystems, Jazz Pharmaceuticals; Financial Interests, Personal, Other, Advisory Board and Consulting: Daiichi Sankyo, Inc., AstraZeneca, Novocure, Eli Lilly, Oncocyte, Novartis, Regeneron, Janssen Oncology, Sanofi group of companies, Molecular Axiom, Amgen, G1 Therapeutics, Bristol Myers Squibb, MorphoSys, Pfizer; Financial Interests, Personal, Other, Consulting, lectures, advising: Platformq; Financial Interests, Personal, Other, Consulting, advising, lectures: HMP Global, MJH Associates, Med Learning, Clinical Care Options, Physicians Educational Resources, Curio Sciences, Vaniam Group, Medscape, Projects in Knowledge, Aptitude Health, MOASC, SITC; Financial Interests, Personal, Invited Speaker: Research to Practice, DAVA, Research to Practice; Financial Interests, Personal, Full or part-time Employment, EmploymentImmediate family member (wife): Boston Scientific; Financial Interests, Personal, Stocks/Shares, Stock (<5% equity)Immediate family member (wife): Boston Scientific; Financial Interests, Institutional, Research Grant, Local PI for multiple trials and Global PI, as well as steering committee chair for U303: Daiichi Sankyo, Inc.; Financial Interests, Institutional, Research Grant, Local PI for multiple trials: Calithera, AstraZeneca; Financial Interests, Institutional, Research Grant, Local PI and externally sponsored research grant: Dracen; Financial Interests, Institutional, Research Grant, Local PI: WindMIL, Effector Therapeutics; Financial Interests, Institutional, Research Grant, Local PI for multiple trials and global PI for multiple trials: Duality Biologics; Financial Interests, Institutional, Research Grant, 2019 Career Development Award: LUNGevity; Financial Interests, Institutional, Research Grant, NIH-NCI K08 CA245249: NIH/NCI; Non-Financial Interests, Personal, Member: ASCO, ESMO, IASLC, AACR. 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, Boehringer; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Personal, Other, lectures: AICME; Financial Interests, Personal, Other, Lectures: CCO; Financial Interests, Personal, Member of Board of Directors, Board member: Stab Therapeutics; Financial Interests, Personal, Other, spinn off (I have arounfd 8% of stocks): Altum sequencing; Financial Interests, Personal, Ownership Interest, spin-off (10%): Stab Therapeutics; 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, Cantargia; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Personal, Other, Member: AACR, ASCO, ESMO; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, President. 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Pérol: Financial Interests, Personal, Advisory Board, Advisory board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GSK, Esai, Ipsen, Novocure, AbbVie, AnHeart Therapeutics, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Symposium: Roche, AstraZeneca, MSD, BMS, Boehringer Ingelheim, Takeda, Illumina, Pfizer, Medscape; Financial Interests, Personal, Advisory Board, Expert Testimony: AstraZeneca; Financial Interests, Personal, Steering Committee Member, Steering Committee member: LILLY; Financial Interests, Institutional, Local PI, Local PI: AbbVie, Amgen, AnHeart Therapeutics, Apollomics, Arrivent Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Innate Pharma, Roche; Financial Interests, Institutional, Research Grant, Resarch grant: AstraZeneca, Boehringer Ingelheim, Roche, Takeda; Financial Interests, Personal, Trial Chair, Trial Chair: AnHeart Therapeutics; Financial Interests, Personal, Steering Committee Member, IDMC Chair: Pharmamar, Sophia Genetics; Financial Interests, Personal, Steering Committee Member, Steering Committee Member: Roche; Financial Interests, Personal, Other, DMSB: Roche. 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Sugawara: Financial Interests, Personal, Other, Lecture fee: AstraZeneca, Chugai Pharma, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Ono Pharmaceutical, MSD K.K, Kyowa Kirin, Takeda, Nippon Kayaku, Merck, Amgen, Thermo Fisher Scientific; Financial Interests, Personal, Other, Lecture Fee: Eisai, Sysmex; Financial Interests, Institutional, Local PI: AstraZeneca, Chugai Pharma, MSD K.K, Daiichi Sankyo, Bristol Myers Squibb, AnHeart, Ono Pharmaceutical, Nippon Boehringer Ingelheim, AbbVie, Parexel International, Amgen, Taiho Pharmaceutical, Accerise, A2 Healthcare, EPS Corporation, Syneos Health, PPD-SNBL. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo K.K, Eli Lilly Japan K.K, Merck Biopharma Co. 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Ltd, Eli Lilly Japan K.K, Pfizer, AstraZeneca K.K, Daiichi Sankyo Co.Ltd; Financial Interests, Personal, Royalties, Currently no provided: Sysmex; Financial Interests, Personal, Steering Committee Member: Janssen Pharmaceutical K.K., GSK plc., Daiichi Sankyo, Inc.; Financial Interests, Institutional, Local PI: IQVIA Services Japan K.K, Syneos Health Clinical K.K., EPS Corporation., Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., MSD K.K., Amgen Inc., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb Company, Janssen Pharmaceutical K.K., CMIC CO., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Kobayashi Pharmaceutical Co., Ltd., Pfizer Japan Inc., AbbVie Inc., A2 Healthcare Corp., Eli Lilly Japan K.K., Medpace Japan KK, EPS International Co., Ltd,., Covance Japan Inc., EP-CRSU Co., Ltd., GSK K.K., Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., PRA Health Sciences Inc., Astellas Pharma Inc., Ascent Development Services, AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Novartis Pharma K.K., Merck Biopharma Co., Ltd, Mochida Pharmaceutical Co., Ltd., Japan Clinical Research Operations; Financial Interests, Institutional, Research Grant: Japanese Gastric Cancer Association, Clinical Research Support Center Kyushu, Japan Clinical Caner Research Organization, Ono Pharmaceutical Co.,Ltd., Medical Research Support, Eisai Co., Ltd, Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Bayer Yakuhin, Ltd, Kyowa Kirin Co.,Ltd.; Financial Interests, Institutional, Funding: SRL Medisearch Inc., Eisai Inc., Thoracic Oncology Research Group(TORG), West Japan Oncology Group (WJOG), Comprehensive Support Project for Oncological Research of Breast Cancer (CSPOR-BC), Mebix, Inc.; Non-Financial Interests, Personal, Member: West Japan Oncology Group, Japanese Society of Medical Oncology. 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, Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen; Financial Interests, Personal, Member of Board of Directors: J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; 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, PDX, PDO, PDC Licensing Contract – not patent: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, 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, JINTSbio, Hanmi, Vertical Bio AG, National Research Foundation of Korea, KHIDI, Therapex; Other, Personal, Other, Founder: DAAN Biotherapeutics; Other, Personal, Other, Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Liangyihui Network Technology Co., Ltd. G. Blumenschein: Financial Interests, Personal, Advisory Board: AbbVie, Adicet, Amgen, Ariad, Bayer, Clovis Oncology, AstraZeneca, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Instil Bio, Genentech, Genzyme, Gilead, Lilly, Janssen, MedImmune, Merck, Novartis, Roche, Sanofi, Tyme Oncology, Xcovery, Virogin Biotech, Maverick Therapeutics, BeiGene, Regeneron, Cytomx Therapeutics, Intervenn Biosciences, Onconova Therapeutics, Seagen, Scorpion Therapeutics; Financial Interests, Personal, Full or part-time Employment, Immediate family member employed: Johnson & Johnson/Janssen; Financial Interests, Personal, Stocks/Shares: Viirogin Biotech; Financial Interests, Institutional, Local PI: CytomX Therapeutics, Duality Biologics, Mythic Therapeutics, Takeda, Aulos Bioscience, Seagen, Amgen, Bayer, Exelixis, Daiichi Sankyo, GSK, Immatics, Immunocore, Incyte, Kite Pharma, Macrogenics, Torque, AstraZeneca, Bristol Myers Squibb, Celgene, Genentech, MedImmune, Merck, Roche, Sanofi, Xcovery, Tmunity Therapeutics, Regeneron, Repertoire Immune Medicines, Verastem; Financial Interests, Institutional, Coordinating PI: Adaptimmune, Novartis; Financial Interests, Institutional, Trial Chair: BeiGene; Non-Financial Interests, Personal, Principal Investigator: BeiGene; Non-Financial Interests, Personal, Member: ASCO, AACR, SITC, IASLC. E. Shum: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Boehringer Ingelheim, Janssen, Regeneron, Bristol Myers Squibb; Financial Interests, Institutional, Funding: Delfi Diagnostics. Y. Goto: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant Health Inc., 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; Financial Interests, Personal and Institutional, Coordinating PI: Chugai, Novartis, Pfizer; Financial Interests, Institutional, Coordinating PI: Guardant Health; Financial Interests, Personal and Institutional, Local PI, NA: Preferred Network; Financial Interests, Institutional, Other, NA: IQVIA; Financial Interests, Institutional, Funding, NA: MSD, AstraZeneca; Financial Interests, Institutional, Funding: Astellas Pharma, Abbvie, Amgen, Syneos, Sysmex, CMIC, Bayer Pharm, MedPace, Janssen Pharma, Ono Pharm, Takeda, Clinical Research Support Center Kyushu, SATOMI; Non-Financial Interests, Personal, Member of Board of Directors: Cancer Net Japan, JAMT. H. Zebger-Gong: Financial Interests, Personal, Full or part-time Employment, full-time employee: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares, stock options as an employee: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares, stocks during previous period as a former employee: Bayer. K. Lakshminarayanan: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. D. Uema: Financial Interests, Personal, Full or part-time Employment, Senior Medical Director: Daiichi Sankyo. I. Okamoto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb, Takeda Pharmaceutical, Daiichi Sankyo, MSD, Pfizer, Taiho Pharmaceutical, Novartis; Financial Interests, Institutional, Local PI: Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, GSK, MSD, Taiho Pharmaceutical, Novartis. W. Gu: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo.