Abstract 59P
Background
The phase III TROPION-Lung01 trial (NCT04656652) evaluated Dato-DXd, a TROP2-directed antibody-drug conjugate, in patients with previously treated advanced NSCLC. The study met its dual primary endpoint of progression-free survival (PFS) in the intent-to-treat population with a significant improvement vs docetaxel (hazard ratio [HR] 0.75; 95% CI, 0.62-0.91; p = 0.004). Interim overall survival (OS) was not mature nor statistically significant, however favored Dato-DXd. Efficacy was primarily attributed to patients with NSQ histology. We report efficacy and safety in the NSQ subgroup from TROPION-Lung01.
Methods
Patients were randomized 1:1 to Dato-DXd 6 mg/kg or docetaxel 75 mg/m2 every 3 weeks, and histology was a stratification factor. PFS and OS by histology were prespecified subgroup analyses; NSQ safety analysis was post hoc. PFS and tumor response were assessed per RECIST 1.1 by blinded independent central review (BICR).
Results
Among 299 patients randomized to Dato-DXd and 305 randomized to docetaxel, 234 in each arm had NSQ histology. At data cutoff (March 29, 2023) median study follow-up was 12.9 months (Dato-DXd) and 12.7 months (docetaxel). In the NSQ subgroup, improved PFS was seen with Dato-DXd vs docetaxel (HR [95% CI], 0.63 [0.51-0.79]); median 5.5 vs 3.6 months. Additional efficacy is shown in the table. In the NSQ subgroup, any grade treatment-related adverse events (TRAEs) occurred in 88% of patients in each treatment arm, with Grade ≥3 events in 22% treated with Dato-DXd and 41% treated with docetaxel. TRAEs associated with dose reduction occurred in 21% and 30% of patients, respectively; TRAEs led to discontinuation in 9% and 12% of patients, respectively. Table: 59P
Efficacy of Dato-DXd in NSQ NSCLC
| NSQ NSCLCa | Dato-DXd (n = 234) | Docetaxel (n = 234) |
| PFSb,c | ||
| Median (95% CI), mo | 5.5 (4.3-6.9) | 3.6 (2.9-4.2) |
| HR (95% CI) | 0.63 (0.51-0.79) | |
| 6-month PFS,b % (95% CI) | 47 (40-53) | 28 (22-35) |
| OS (interim)c | ||
| Median (95% CI), mo | 13.4 (12.1-16.4) | 11.4 (10.1-13.8) |
| HR (95% CI) | 0.79 (0.60-1.02) | |
| ORRb, n (%) | 73 (31) | 30 (13) |
| (95% CI) | (25-38) | (9-18) |
| CR | 4 (2) | 0 |
| PR | 69 (30) | 30 (13) |
| Duration of responsec | ||
| Median (95% CI), mo | 7.7 (5.6-11.1) | 5.6 (5.4-6.0) |
| Disease control rate,d n (%) | 188 (80) | 143 (61) |
| (95% CI) | (75-85) | (55-67) |
aHistology per case report forms; bPer BICR; cKaplan-Meier method; dCR + PR + stable disease + [non-CR/non-PD] CR, complete response; PD, progressive disease; PR, partial response
Conclusions
In TROPION-Lung01, Dato-DXd demonstrated clinically meaningful PFS benefit vs docetaxel in the subgroup of patients with NSQ NSCLC. Safety profile was manageable. OS assessment continues to final analysis.
Editorial acknowledgement
Editorial support was provided by Isobel Markham of Core Medica, London.
Legal entity responsible for the study
Daiichi Sankyo.
Funding
Daiichi Sankyo and AstraZeneca.
Disclosure
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, Personal, Other, Family member is an employee: AstraZeneca. I. Okamoto: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, AstraZeneca; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Chugai Pharma, Lilly, Bristol Myers Squibb, MSD Oncology, AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Lilly, Bristol Myers Squibb, MSD Oncology, AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical. A.E. Lisberg: Financial Interests, Personal, Full or part-time Employment: Boston Scientific; Financial Interests, Personal, Stocks/Shares: Boston Scientific; Financial Interests, Personal, Research Grant: Daiichi Sankyo, Calithera Biosciences, AstraZeneca, Dracen Pharmaceuticals, WindMIL, eFFECTOR Therapeutics, Duality Biologics; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Leica Biosystems, Jazz Pharmaceuticals, Novocure, Pfizer, MorphoSys, Eli Lilly, Oncocyte, Novartis, Regeneron, Janssen oncology, Sanofi group of companies, G1 Therapeutics, Molecular Axiom, Amgen, IQVIA, Bayer, Daiichi Sankyo. E. Pons-Tostivint: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Sanofi, Takeda; Non-Financial Interests, Institutional, Principal Investigator, Local: Amgen, Bristol Myers Squibb, Daiichi Sankyo, PDC line, Sanofi, Takeda. R. Cornelissen: Financial Interests, Personal, Advisory Board: Spectrum, Janssen; Financial Interests, Personal, Invited Speaker: Ad Liberum, MSD; Financial Interests, Personal, Advisory Role: MSD. L. Paz-Ares: Financial Interests, Personal, Other, Consultory fees: Lilly, MSD, Roche, PharmaMar, Merck KGaA (Darmstadt, Germany), AstraZeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, Daiichi Sankyo; Financial Interests, Personal, Other, Payment for honoraria for lectures, presentations, speakers bureaus, educational events: AstraZeneca, Janssen, Merck; Financial Interests, Personal, Other, Payment for honoraria for lectures, presentations, speakers bureaus, educational events: Mirati; Financial Interests, Personal, Member of Board of Directors: Altum sequencing, Stab Therapeutics. D. Vicente Baz: Financial Interests, Personal, Advisory Role: Merck KGaA, Darmstadt, Germany, AstraZeneca, Roche, Pfizer, MSD, Bristol Myers Squibb, Novartis, Takeda; Financial Interests, Personal, Other, payment or honoraria: AstraZeneca, Pfizer, MSD, BMS, Gilead; Financial Interests, Personal, Other, Travel support for attending meetings: AstraZeneca, Pfizer, BMS; Financial Interests, Personal, Advisory Board: Gilead, MSD. S. Sugawara: Financial Interests, Personal, Speaker’s Bureau: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai Pharma, Kyowa Kirin, Lilly, Merck, MSD K.K, Nippon Boehringer Ingelheim, Nippon Kayaku, Novartis, Ono Pharmaceutical, Otsuka, Pfizer, Taiho Pharmaceutical, Takeda, Thermo Fisher Scientific, TOWA PHARMACEUTICAL; Financial Interests, Personal, Principal Investigator, Local: AnHeart, AstraZeneca, Bristol Myers Squibb, Chugai Pharma, Daiichi Sankyo, MSD K.K, Nippon Boehringer Ingelheim, Ono Pharmaceutical. M. Pérol: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, MSD, Boehringer Ingelheim, Takeda, Illumina, Pfizer, MEDSCAPE; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, BMS, Lilly, Novartis, Takeda, Gritstone, Sanofi, Pfizer, Amgen, Janssen, GSK, ESAI, IPSEN; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, AstraZeneca, Roche, Takeda; Financial Interests, Personal, Other, Steering Committee Member: Roche; Financial Interests, Personal, Other, Data Monitoring Safety Board: Roche. C. Mascaux: Financial Interests, Institutional, Principal Investigator, Coordinating: GSK; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Bristol Myers Squibb, Pfizer, MSD, Sanofi, Takeda, Amgen, Janssens; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Kephren, Bristol Myers Squibb, Pfizer, MSD, Sanofi, Takeda, Amgen, Janssens; Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Kephren, Bristol Myers Squibb, Pfizer, MSD, Sanofi, Takeda, Amgen, Janssens. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Personal, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. Y. Le Guen: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca. J. Sands: Financial Interests, Personal, Invited Speaker: Arcus, AstraZeneca, Daiichi Sankyo, PharmaMar, Amgen, Boehringer Ingelheim, Curadev; Financial Interests, Personal, Advisory Role: Arcus, AstraZeneca, Daiichi Sankyo, PharmaMar, Amgen, Boehringer Ingelheim, Curadev; Non-Financial Interests, Institutional, Principal Investigator, Local: AstraZeneca, Daiichi Sankyo, PharmaMar, Amgen, Boehringer Ingelheim, Phanes, Legend, Genentech. M. Chargualaf: Other, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Zhang: Financial Interests, Personal, Stocks/Shares, I’m an employee of DSI and have stocks of DS.: Daiichi Sankyo, Inc. P. Howarth: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. D. Uema: Other, Personal, Sponsor/Funding: Daiichi Sankyo. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, Yuhan, MSD, Merck, Amgen, Daiichi Sankyo, Alpha pharmaceuticals, Pfizer, Roche, BMS. All other authors have declared no conflicts of interest.