Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations

NCT05687266 · tracked via the Priya Life Science USA tracker

Sponsor

AstraZeneca

Phase

Phase 3

Started

2022-12-29

Last updated

2026-04-22

Condition(s) studied

NSCLC

Investigational drug(s) / intervention(s)

Datopotamab deruxtecanDurvalumabCarboplatinPembrolizumabCisplatinPemetrexedPaclitaxel

Datopotamab deruxtecan: Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Durvalumab: Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Carboplatin: Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Pembrolizumab: Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle for a maximum of 35 cycles or 2 years (whichever occurs first).

Cisplatin: Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Pemetrexed: Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.

Paclitaxel: Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Study summary

This is a Phase III, randomized, open-label, multicenter, global study to compare the efficacy and safety of Datopotamab Deruxtecan (Dato-DXd) in combination with durvalumab and carboplatin compared with pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment of adults with stage IIIB, IIIC, or IV NSCLC without actionable genomic alterations (including sensitizing EGFR mutations, and ALK and ROS1 rearrangements).

Eligibility

Sex

ALL

Min age

18 Years

Max age

130 Years

Healthy volunteers

Inclusion: * 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: * 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.

Primary outcome measure(s)

Progression-Free Survival (PFS) by blinded independent central review (BICR) in the non-squamous TROP2 biomarker positive population — Approximately 3 years
PFS is deﬁned as time from randomisation until progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) as assessed by BICR, or death due to any cause.
Overall Survival (OS) in the non-squamous TROP2 biomarker positive population — Approximately 5 years
OS is defined as the time from randomisation until the date of death due to any cause.
PFS by BICR in the non-squamous population — Approximately 3 years
PFS is deﬁned as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
OS in the non-squamous population — Approximately 5 years
OS is deﬁned as the time from randomisation until the date of death due to any cause.

Trial sites (254)

Facility	City	Region
Research Site	Phoenix	Arizona
Research Site	Tucson	Arizona
Research Site	Hot Springs	Arkansas
Research Site	Little Rock	Arkansas
Research Site	Springdale	Arkansas
Research Site	Fountain Valley	California
Research Site	Los Angeles	California
Research Site	Orange	California
Research Site	Boulder	Colorado
Research Site	Fort Myers	Florida
Research Site	Jacksonville	Florida
Research Site	St. Petersburg	Florida
Research Site	West Palm Beach	Florida
Research Site	Hinsdale	Illinois
Research Site	Fort Wayne	Indiana
Research Site	Bettendorf	Iowa
Research Site	Iowa City	Iowa
Research Site	Waukee	Iowa
Research Site	Baton Rouge	Louisiana
Research Site	Covington	Louisiana
Research Site	Duluth	Minnesota
Research Site	Rochester	Minnesota
Research Site	Hannibal	Missouri
Research Site	Lincoln	Nebraska
Research Site	Lincoln	Nebraska
Research Site	Clifton Park	New York
Research Site	Asheville	North Carolina
Research Site	Canton	Ohio
Research Site	Columbus	Ohio
Research Site	Maumee	Ohio
Research Site	Tulsa	Oklahoma
Research Site	Portland	Oregon
Research Site	Salem	Oregon
Research Site	Philadelphia	Pennsylvania
Research Site	Philadelphia	Pennsylvania
Research Site	Philadelphia	Pennsylvania
Research Site	York	Pennsylvania
Research Site	Watertown	South Dakota
Research Site	Memphis	Tennessee
Research Site	Dallas	Texas

+ 214 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05687266 on ClinicalTrials.gov ↗ ← All trials in the USA