LBA12 - Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): Results of the randomized phase III study TROPION-Lung01

Background

Dato-DXd is a novel TROP2-directed antibody-drug conjugate under clinical investigation in multiple tumor types. This is the first report of TROPION-Lung01 (NCT04656652), a randomized, global, open-label, phase 3 study of Dato-DXd vs docetaxel (DTX) in pretreated patients (pts) with adv/met NSCLC with or without actionable genomic alterations (AGAs).

Methods

Pts were randomized 1:1 to Dato-DXd 6 mg/kg or DTX 75 mg/m² Q3W. Dual primary endpoints were progression-free survival (PFS; by blinded independent central review [BICR]) and overall survival (OS). Secondary endpoints included objective response rate (ORR), duration of response (DOR), and safety.

Results

604 pts were included in the full analysis set (FAS); 43.1% had received ≥2 prior lines of systemic therapy. Median age was 64 y (range, 24-88). PFS was significantly improved with Dato-DXd over DTX in the FAS (HR, 0.75; 95% CI, 0.62-0.91; P=.004; median, 4.4 vs 3.7 mo). Confirmed ORRs were 26.4% (Dato-DXd) and 12.8% (DTX), with median DORs of 7.1 and 5.6 mo. Longer median PFS was observed in the prespecified non-squamous histology subgroup (NSQ; 5.6 vs 3.7 mo). Median treatment duration was 4.2 mo (range, 0.7-18.3 mo) for Dato-DXd and 2.8 mo (range, 0.7-18.9 mo) for DTX. The most common treatment-emergent adverse events (TEAEs) seen with Dato-DXd were stomatitis (49.2%, mostly grade [gr] 1/2) and nausea (37%). Adjudicated drug-related interstitial lung disease gr ≥3 occurred in 3.4% of pts with Dato-DXd vs 1.4% with DTX. Fewer drug-related gr ≥3 TEAEs and AEs leading to dose reduction or discontinuation were seen with Dato-DXd vs DTX. Table: LBA12

^aBy BICR. ^bPFS P value boundary = .008. ^cNo. of pts in the Dato-DXd and DTX arms. ^dNo. of pts treated. ^ePer Investigator; adjudicated data will be presented.

Conclusions

PFS was significantly improved with Dato-DXd over DTX in pts with pretreated adv/met NSCLC. NSQ patients appeared to derive the most benefit. Dato-DXd was well tolerated, with a manageable safety profile. The trial is continuing until the final OS analysis. M-J. Ahn and A. Lisberg have equally contributed to the study.

Clinical trial identification

NCT04656652.

Editorial acknowledgement

Medical writing support was provided by Melanie Vishnu, PhD, Ari Simenauer, PhD, and Martin Haschak, PhD, of Nucleus Global, and was funded by Daiichi Sankyo, Inc. Editorial support was provided in accordance with good publication practice guidelines (ismpp.org/gpp-2022).

Legal entity responsible for the study

Daiichi Sankyo, Inc.

Funding

Daiichi Sankyo, Inc.

Disclosure

A. Lisberg: Financial Interests, Personal, Other, All support for the present publication: NIH-NCI K08 CA245249-01A1; LUNGevity 2019 Career Development Award; Financial Interests, Personal, Other, Grants or contracts from any entity: NIH-NCI K08 CA245249-01A1; LUNGevity 2019 Career Development Award; Financial Interests, Institutional, Other, Grants or contracts from any entity: Daiichi Sankyo; Calithera; AstraZezeca; Dracen; WindMIL; Duality Biologics; Effector Therapeutics; Financial Interests, Personal, Other, Consulting fees: AstraZezeca; Bristol-Myers Squibb; Leica Biosystems; Jazz Pharmaceuticals; Novocure; Pfizer; MorphoSys; Eli-Lilly; Oncocyte; Novartis; Regeneron; Janssen oncology; Sanofi group of companies; Molecular Axiom; Amgen; Financial Interests, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Platformq; HMP Global; MJH Associates; Med Learning; Clinical Care Options; Physicians Educational Resources; Curio Sciences; Vaniam Group; Medscape; Projects in Knowledge; Aptitude Health; Financial Interests, Personal, Other, Support for attending meetings and/or travel: AstraZeneca; Bristol-Myers Squibb; Novocure; Pfizer; Financial Interests, Other, Participation on a Data Safety Monitoring Board or Advisory Board: AstraZeneca; Bristol-Myers Squibb; Leica Biosystems; Jazz Pharmaceuticals; Novocure; Pfizer; MorphoSys; Eli-Lilly; Oncocyte; Novartis; Regeneron; Janssen oncology; Sanofi group of companies; Amgen; Financial Interests, Other, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Daiichi Sankyo; Duality Biologics; AstraZeneca; Financial Interests, Stocks or ownership, (immediate family member): Boston Scientific; Financial Interests, Full or part-time Employment, (immediate family member): Boston Scientific. M. Ahn: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, YUHAN, Amgen, Roche, Pfizer, Alpha pharmaceuticals, Takeda, VORONOI, EUTILEX, Daiichi Sankyo, ARCUS. 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. 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; Non-Financial Interests, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Family member is an employee: AstraZeneca. 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. S. 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, Towa Pharmaceutical, Takeda, Nippon Kayaku, Otsuka, Merck, Amgen, Thermo Fisher Scientific, AbbVie; Financial Interests, Institutional, Local PI: AstraZeneca, Chugai Pharma, MSD K.K, Daiichi Sankyo, Bristol-Myers Squibb, AnHeart, Ono Pharmaceutical, Nippon Boehringer Ingelheim. 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. S. Kitazono: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Ono Pharmaceutical Co, Chugai Pharmaceutical Co.,Ltd. H. Hayashi: Financial Interests, Personal, Invited Speaker: Amgen K.K., AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Merck Biopharma Co. Ltd., MSD K.K., Novartis Pharmace; Financial Interests, Personal, Advisory Board: AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., and Merck Biopharma Co. Ltd.; Financial Interests, Personal, Writing Engagement: Guardant Health; Financial Interests, Institutional, Funding: AstraZeneca K.K., Astellas Pharma Inc., MSD K.K., Ono Pharmaceutical Co. Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novartis Pharma K.K., Pfizer Japan Inc., Bristol-Myers Squibb Co. Ltd., Eli Lilly Japan K.K., Chugai Pharmaceutical Co. Ltd., Daiichi Sank. 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, Phanes, Legend, Amgen, Daiichi Sankyo, Lilly. R. Hall: Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals; Financial Interests, Institutional, Local PI: Daiichi - Sankyo, Lilly, Genentech, Merck. Y. Zhang: Financial Interests, Personal, Stocks/Shares, I’m an employee of Daiichi Sankyo, Inc. and have its stocks from the employment.: Daiichi Sankyo, Inc. H. Zebger-Gong: Other, Personal and Institutional, Full or part-time Employment, Full-time employment: Daiichi Sankyo; Other, Personal and Institutional, Stocks or ownership, Stock options: Daiichi Sankyo; Other, Personal, Stocks or ownership, Stocks: Bayer. D. Uema: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. I. Okamoto: Financial Interests, Personal, Speaker, Consultant, Advisor: CHUGAIPHARMACEUTICAL CO., LTD., ONO PHARMACEUTICAL CO., LTD., TAIHO PHARMACEUTICAL CO., LTD., Nippon Boehringer Ingelheim Co., Ltd, AstraZeneca, Eli Lilly Japan K.K., Takeda Pharmaceutical, Novartis Pharma K.K., Daiichi Sankyo, Chugai Pharma, Lilly, Bristol-Myers Squibb, MSD Oncology, AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical. All other authors have declared no conflicts of interest.