NCT05687266

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

A Phase III, Randomised, Open-label, Multicentre, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab and Carboplatin Versus Pembrolizumab in Combination With Platinum-based Chemotherapy for the First-line Treatment of Patients With Locally Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (D926NC00001; AVANZAR)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,350 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 130 Years
• Healthy volunteers: Not accepted

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).

Detailed description

Participants with locally advanced or metastatic NSCLC without actionable tumor tissue genomic alterations and confirmed to meet all eligibility criteria will be randomized in a 1:1 ratio to Dato-DXd in combination with durvalumab and carboplatin versus pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment. The primary objectives of the study are to demonstrate 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

Conditions

• NSCLC

Interventions

Type	Name	Description
DRUG	Datopotamab deruxtecan	Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
DRUG	Durvalumab	Intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
DRUG	Carboplatin	Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.
DRUG	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).
DRUG	Cisplatin	Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.
DRUG	Pemetrexed	Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
DRUG	Paclitaxel	Intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for up to 4 cycles.

Timeline

• Start date: 2022-12-29
• Primary completion: 2027-11-01
• Completion: 2027-11-01
• First posted: 2023-01-18
• Last updated: 2026-03-13

Locations

254 sites across 23 countries: United States, Austria, Brazil, Bulgaria, Canada, China, France, Germany, Greece, Hungary, India, Italy, Japan, Mexico, Peru, Poland, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, Vietnam

Regulatory

• FDA-regulated drug study