A Study of Dato-DXd in Combination With Durvalumab and Carboplatin for First-line Treatment of Advanced NSCLC Without Actionable Genomic Alterations

Phase 3

Active, not recruiting

• Conditions: Non-Small Cell Lung Cancer (NSCLC)

• Registration Number: 2023-505993-14-00
• Lead Sponsor: Astrazeneca AB

Brief Summary

To demonstrate the superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy by assessment of the following:

1. PFS by BICR in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC

2. OS in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC

3. PFS by BICR in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC

4. OS in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-06-04
• Last Update Posted: 2025-05-26

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 442

Inclusion Criteria

Participants ≥ 18 years at screening

Histologically or cytologically documented NSCLC that at the time of randomisation is Stage IIIB or IIIC disease not amenable to surgical resection or definitive chemoradiation or Stage IV metastatic disease

Lacks sensitising EGFR tumour tissue mutation and ALK and ROS1 rearrangements and has no documented tumour genomic alterations in NTRK, BRAF, RET, MET or other actionable driver oncogenes with approved and available therapies (actionable genomic alterations). Testing is not required for tumors with squamous histology, with exceptions.

ECOG PS of 0 or 1

Archival tumour tissue

Has adequate bone marrow reserve and organ function within 7 days before randomization

Exclusion Criteria

Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC

History of another primary malignancy with exceptions

Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade ≤ 1 or baseline, with exceptions.

Spinal cord compression or clinically or radiologically active brain metastases

History of leptomeningeal carcinomatosis.

Known active or uncontrolled hepatitis B or C virus infection.

Uncontrolled or suspected infection requiring IV antibiotics, antivirals, or antifungals.

Clinically significant corneal disease

History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening

Study & Design

• Study Type: Not specified
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Overall Survival in non-squamous full analysis set, defined as the time from randomisation until the date of death due to any cause		Overall Survival in non-squamous full analysis set, defined as the time from randomisation until the date of death due to any cause
Progression-Free Survival as assessed by BICR in non-squamous TROP2 biomarker positive analysis set, defined as time from randomisation until progression per RECIST 1.1 or death due to any cause.		Progression-Free Survival as assessed by BICR in non-squamous TROP2 biomarker positive analysis set, defined as time from randomisation until progression per RECIST 1.1 or death due to any cause.
Overall Survival in non-squamous TROP2 biomarker positive analysis set, defined as the time from randomisation until the date of death due to any cause		Overall Survival in non-squamous TROP2 biomarker positive analysis set, defined as the time from randomisation until the date of death due to any cause
Progression-Free Survival as assessed by BICR in non-squamous full analysis set, defined as time from randomisation until progression per RECIST 1.1 or death due to any cause.		Progression-Free Survival as assessed by BICR in non-squamous full analysis set, defined as time from randomisation until progression per RECIST 1.1 or death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate as determined by BICR, Duration of Response as assessed by BICR and investigator assessment, Progression-Free Survival as assessed by investigator assessment, and Progression-Free Survival 2 in the non-squamous population		Objective Response Rate as determined by BICR, Duration of Response as assessed by BICR and investigator assessment, Progression-Free Survival as assessed by investigator assessment, and Progression-Free Survival 2 in the non-squamous population
Pharmacokinetics and immunogenicity		Pharmacokinetics and immunogenicity
Progression-Free Survival as assessed by BICR, Overall Survival, Objective Response Rate as determined by BICR, Duration of Response as assessed by BICR and investigator assessment, Progression-Free Survival as assessed by investigator assessment, and Time to second progression or death in ITT and TROP2 biomarker-defined populations		Progression-Free Survival as assessed by BICR, Overall Survival, Objective Response Rate as determined by BICR, Duration of Response as assessed by BICR and investigator assessment, Progression-Free Survival as assessed by investigator assessment, and Time to second progression or death in ITT and TROP2 biomarker-defined populations
Clinical Outcome Assessments as measured by the NSCLC-SAQ and PROMIS Physical Function short form 8c.		Clinical Outcome Assessments as measured by the NSCLC-SAQ and PROMIS Physical Function short form 8c.

Trial Locations

Locations (80)

LKH Feldkirch Interne E at LKH Rankweil; 🇦🇹 Rankweil, Austria

Medizinische Universität Graz; 🇦🇹 Graz, Austria

Krankenhaus Nord Klinik Floridsdorf; 🇦🇹 Vienna, Austria

Allgemeines Krankenhaus Der Stadt Wien Universitatskliniken; 🇦🇹 Vienna, Austria

St. Luke's Hospital S.A.; 🇬🇷 Thessaloniki, Greece

Athens Medical Center S.A.; 🇬🇷 Thessaloniki, Greece

Henry Dunant Hospital Center; 🇬🇷 Athens, Greece

Metropolitan Hospital; 🇬🇷 Pireas, Greece

Thoracic General Hospital Of Athens I Sotiria; 🇬🇷 Athens, Greece

Hämato-Onkologie Hamburg; 🇩🇪 Hamburg, Germany

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LKH Feldkirch Interne E at LKH Rankweil

🇦🇹Rankweil, Austria

Thomas Winder

Site contact

004355223032691

thomas.winder@lkhf.at