1505TiP - TROPION-Lung07: A phase III trial of datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy in advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC) with PD-L1 expression

Background

Immunotherapy has improved survival in patients (pts) with adv/met NSCLC. However, outcomes remain poor in pts with PD-L1 expression <50%, and more efficacious treatments are needed. Dato-DXd is an antibody-drug conjugate composed of a TROP2 directed monoclonal antibody covalently linked to a highly potent cytotoxic payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. In the phase 1b TROPION-Lung02 trial, Dato-DXd + pembro ± Pt-CT had tolerable safety and promising antitumor activity in pts with adv/met NSCLC, notably as 1L therapy and irrespective of PD-L1 levels. Here, we describe the TROPION-Lung07 trial of Dato-DXd + pembro ± Pt-CT in pts with adv/met NSCLC without actionable genomic alterations (AGA) and PD-L1 expression <50%.

Trial design

TROPION-Lung07 (NCT05555732) is a global, randomized, open-label, phase 3 trial of 1L Dato-DXd + pembro ± Pt-CT in pts with nonsquamous adv/met NSCLC without AGA with PD-L1 expression <50%. Dato-DXd + pembro ± Pt-CT will be compared with pemetrexed + pembro + Pt-CT. Approximately 975 pts will be randomized 1:1:1 to Dato-DXd 6 mg/kg + pembro 200 mg (max, 35 cycles) ± Pt-CT (cisplatin 75 mg/m² or carboplatin area under the curve 5; max, 4 cycles) every 3 weeks (Q3W) or pemetrexed 500 mg/m² + pembro 200 mg + Pt-CT Q3W. Pts will be stratified by PD-L1 levels, Eastern Cooperative Oncology Group performance status, geographic region, and investigator choice of Pt-CT. Pts must have stage IIIB/C NSCLC ineligible for resection or definitive chemoradiation or stage IV disease and must not have received prior systemic therapy for adv/met NSCLC. The primary endpoints are progression-free survival by blinded independent central review and overall survival. Secondary endpoints include objective response rate (ORR), duration of response, time to response, disease control rate, and safety. Pt-reported outcomes, pharmacokinetics, and biomarkers will be explored. Enrollment is currently ongoing in the United States, Australia, China, Japan, Republic of Korea, Taiwan, and Thailand.

Clinical trial identification

NCT05555732.

Editorial acknowledgement

Medical writing support was provided by Martin Haschak, PhD, of SciMentum, Inc, a Nucleus Holdings Ltd company, 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

I. Okamoto: Financial Interests, Personal, Speaker, Consultant, Advisor: Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd, AstraZeneca, Eli Lilly Japan K.K., Takeda Pharmaceutical Company Limited, Novartis Pharma K.K.; Financial Interests, Institutional, Research Funding: Daiichi Sankyo, Chugai Pharma, Lilly, Bristol Myers Squibb, MSD Oncology, AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical. S. Kuyama: Financial Interests, Other, Honoraria: AstraZeneca K.K., Bristol Myers Squibb Company, Hisamitsu Pharmaceutical Co.,Inc., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Pfizer Japan Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited., Kyowa Kirin Co., Ltd.. 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. S. Lu: Financial Interests, Other, Grants or contracts: AstraZeneca, Hutchison, BMS, Heng Rui, BeiGene, Roche, Hansoh; Financial Interests, Other, Consulting fees: AstraZeneca, Pfizer , Boehringer Ingelheim, Hutchison, MediPharma, Simcere, ZaiLab, GenomiCare , Yuhan Corporation, PrIME Oncology, Menarini, InventisBio Co. Ltd., Roche; Financial Interests, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Roche, Hansoh, Hengrui Therapeutics; Financial Interests, Other, Participation on a Data Safety Monitoring Board or Advisory Board: Roche, Regenron, AstraZeneca, Simcere Zaiming Pharmaceutical Co., Ltd; Financial Interests, Other, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Chinese Lung Cancer Associate, CSCO. F.A. Franke: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, BMS, MSD, Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo, Lilly, Bristol Myers Squibb, MSD Oncology, AstraZeneca, Takeda, Roche, Amgen, Pfizer, Novartis, Gilead, Merck. N. Ren: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks or ownership: Daiichi Sankyo; Financial Interests, Personal, Other, Travel, accommodations, expenses: Daiichi Sankyo. E. Oputa: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks or ownership: PPD, Syneos Health. A.E. Lisberg: Financial Interests, Personal, Full or part-time Employment, Immediate Family Member: Boston Scientific; Financial Interests, Personal, Stocks or ownership, Immediate Family Member: Boston Scientific; Financial Interests, Personal, Other, Consulting or advisory role: AstraZeneca, Bristol Myers Squibb, Leica Biosystems, Jazz Pharmaceuticals , Novocure, Pfizer, MorphoSys , Eli Lilly, Oncocyte, Novartis, Regeneron, Janssen Oncology, Sanofi group of companies; Financial Interests, Institutional, Research Funding: Daiichi Sankyo, Calithera Biosciences, AstraZeneca, Dracen Pharmaceuticals, WindMIL, eFFECTOR Therapeutics. All other authors have declared no conflicts of interest.