1312P - Datopotamab deruxtecan (Dato-DXd) vs docetaxel (DTX) in patients (pts) with advanced nonsquamous (NSQ) non-small cell lung cancer (NSCLC) with brain metastases (mets): Results from TROPION-Lung01

Background

Brain mets are common in pts with NSCLC and are associated with poor prognosis. The phase 3 TROPION-Lung01 trial (NCT04656652) demonstrated a statistically significant improvement in progression-free survival (PFS) with Dato-DXd vs DTX in pts with previously treated advanced NSCLC; efficacy was driven by those with NSQ histology. We present a post hoc analysis of pts with NSQ NSCLC by baseline (BL) brain met status.

Methods

Pts were randomized 1:1 to Dato-DXd 6 mg/kg or DTX 75 mg/m2 every 3 weeks. Pts with clinically stable brain mets, defined as asymptomatic, previously treated or untreated, were eligible. Efficacy per RECIST v1.1, including PFS and objective response rate (ORR) by blinded independent central review, and treatment-related adverse events (TRAEs) were assessed in pts with NSQ NSCLC by BL brain met status.

Results

At data cutoff (Mar 29, 2023), 84/468 pts with NSQ NSCLC had brain mets, 43 of whom were randomized to Dato-DXd and 41 to DTX. Median study follow-up was 12.9 and 12.7 months (mo) for Dato-DXd and DTX. BL characteristics were generally balanced between treatment arms and in pts with and without brain mets. Dato-DXd prolonged PFS vs DTX regardless of brain met status; median PFS was 4.9 vs 3.6 mo in pts with brain mets (hazard ratio [HR] 0.59; 95% CI, 0.35–1.00); 5.7 vs 3.7 mo in pts without brain mets (HR 0.64, 95% CI, 0.50–0.81). ORR was higher for pts receiving Dato-DXd vs DTX in pts with and without brain mets (Table). Fewer grade ≥3 serious TRAEs and dose reductions or discontinuations occurred with Dato-DXd vs DTX regardless of brain met status.

Conclusions

Dato-DXd showed improved efficacy and a manageable safety profile vs DTX in advanced NSQ NSCLC regardless of BL brain met status. Assessment of intracranial activity of Dato-DXd is ongoing. Table: 1312P

∗ NSQ histology

Clinical trial identification

NCT04656652.

Editorial acknowledgement

Medical writing support, under direction of the authors, was provided by Katie Webster and editorial support was provided by Isobel Markham, both of Core, a division of Prime, London, and funded by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo.

Funding

Daiichi Sankyo.

Disclosure

E. Pons-Tostivint: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, BMS, Sanofi, Roche, Daiichi Sankyo; Financial Interests, Institutional, Local PI: AstraZeneca, BMS, Daiichi Sankyo, Sanofi, PDC line, Takeda, Amgen. 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. 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, Member of Board of Directors, President of medical society working to advance lung cancer screening: Rescue Lung Society. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Family member is an employee: AstraZeneca. R. Cornelissen: Financial Interests, Personal, Advisory Board: Spectrum, Johnson and Johnson, MSD, Pierre Faber, BMS; Financial Interests, Personal, Invited Speaker: BMS. M.H. Hong: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Roche; Financial Interests, Personal, Invited Speaker: Merck, Yuhan, Janssen, Takeda, Amgen. L.G. 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Mascaux: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Bristol Myers Squibb, Pfizer, MSD, Amgen; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Roche, Bristol Myers Squibb, Pfizer, Kephren, Janssens, Takeda, Sanofi, Novartis. S. Kitazono: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Ono Pharmaceutical Co, Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Eli Lilly Japan K.K.; Financial Interests, Personal, Advisory Board: Amgen Inc. 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. Ltd., MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd.; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb Co. 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, Member: West Japan Oncology Group, Japanese Society of Medical Oncology. 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, Employment Immediate 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, Member: ASCO, ESMO, IASLC, AACR. O.J. Juan Vidal: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Roche/Genentech, Lilly, Takeda, AstraZeneca, Janssen; Financial Interests, Personal, Other, Travel expenses: MSD; Financial Interests, Personal, Invited Speaker: Bristol Myers Squib, Amgen, Roche/Genentech, Pfizer; Financial Interests, Institutional, Funding: AstraZeneca. Y. Zhang, M. Chargualaf: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc.; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Inc. D. Uema: Financial Interests, Personal, Full or part-time Employment, Senior Medical Director: Daiichi Sankyo. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, MSD, Yuhan, Amgen, Alpha Pharmaceutical, Janssen, Bristol Myers Squibb, Roche, Daiichi Sankyo, Merck, Boronoi. All other authors have declared no conflicts of interest.