509MO - 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 prespecified subgroups including non-squamous histology (NSQ; 5.6 vs 3.7 mo) and AGA (6.8 vs 2.6 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: 509MO

^aBy BICR. ^bPFS P value boundary = .008. ^cNo. of pts in the Dato-DXd and DTX arms. ^dNo. of pts treated.

Conclusions

PFS was significantly improved with Dato-DXd over DTX in pts with pretreated adv/met NSCLC. NSQ and AGA subsets 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.

Clinical trial identification

NCT04656652.

Editorial acknowledgement

Medical writing support was provided by Melanie Vishnu, PhD, of Nucleus Global, Yardley PA.

Legal entity responsible for the study

Daiichi Sankyo.

Funding

Daiichi Sankyo.

Disclosure

M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, MSD, YUHAN, Amgen, ALPHA Pharmaceutical, Janssen, BMS, Roche, Daichi Sankyo, Merck, BOROnoI. A.E. Lisberg: Financial Interests, Personal, Other, Consulting, Lectures or Advisory Role at Bayer, Daiichi Sankyo, Inc., AstraZeneca, Novocure, Eli Lilly, Oncocyte, Novartis, Regeneron, Janssen Oncology, MorphoSys, Sanofi group of companies, Molecular Axiom, Amgen, IQVIA, G1 Therapeutics, Bristol-Myers Squibb, Leica Biosystems, Jazz Pharmaceuticals, Pfizer, Platformq, HMP Global, MJH Associates, Med Learning, Clinical Care Options, Physicians Educational Resources, Curio Sciences, Vaniam Group, Medscape, Projects in Knowledge, Aptitude Health, MOASC, SITC; Grant/Research Support from Daiichi Sankyo, Inc., Calithera, AstraZeneca, Dracen, WindMIL, Duality Biologics, Effector Therapeutics, LUNGevity and NIH/NCI; Funding for the current study by Daiichi Sankyo Inc. and AstraZeneca. L. Paz-Ares: Financial Interests, Personal, Other, Consulting role: Lilly, MSD, Roche, Pharmamar, Merck KGaA (Darmstadt, Germany), AstraZeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, Daichii Sankyo; Financial Interests, Personal, Other, Payment for honoraria for lectures, presentations, speakers bureaus, educational events: AstraZeneca, Janssen, Merck, Mirati; Financial Interests, Personal, Other, Member of the board of directors: Altum sequencing, Stab Therapeutics. R. Cornelissen: Financial Interests, Personal, Advisory Board: Spectrum, Janssen; Financial Interests, Personal, Invited Speaker: Ad Liberum; Financial Interests, Personal, Speaker, Consultant, Advisor: MSD. 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, Personal, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Personal, Other, Family member is an employee: AstraZeneca. E. Pons-Tostivint: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, BMS, Sanofi; No 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, Nippon Boehringer Ingelheim, Ono Pharmaceutical. M. Pérol: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, GRITSTONE, Sanofi, Pfizer, Amgen, Janssen, GSK, ESAI, 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. C. Mascaux: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Kephren, Bristol Myers Squibb, Pfizer, MSD, Sanofi, Takeda, Amgen, Pfizer, Janssen; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Roche, Bristol Myers Squibb, Pfizer, Janssens, Takeda, Sanofi; Financial interests, Institutional, Coordinating PI: GSK. S. Kitazono: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Ono Pharmaceutical Co, Chugai Pharmaceutical CO., LTD. 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., Sysmex Corporation; Financial Interests, Personal and Institutional, Invited Speaker, Research Funding: Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal and Institutional, Invited Speaker, Research Grant: MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Bristol Myers Squibb Company; Financial Interests, Personal, Invited Speaker, Research Grant: Amgen Inc.; 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: Elsai Co., Ltd. R. Hall: Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals; No Financial Interests, Institutional, Local PI: Daiichi Sankyo, Lilly, Genentech, Merck. Y. Zhang: Financial Interests, Personal, Stocks or ownership, I’m an employee of DSI and have stocks of DS.: Daiichi Sankyo, Inc.. H. Zebger-Gong: Other, Institutional, Full or part-time Employment, Full-time employment: Daiichi Sankyo; Other, Personal and Institutional, Stocks/Shares, Stock options: Daiichi Sankyo; Other, Personal, Stocks/Shares, Stock: Bayer. D. Uema: Financial Interests, Personal, Full or part-time Employment, Senior Medical Director: Daiichi Sankyo. All other authors have declared no conflicts of interest.