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NCT05687266PHASE3ACTIVE_NOT_RECRUITING4 endpoints open for prediction

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)

Sponsor: AstraZeneca

Open for Predictions · 4 endpoints

NCT05687266HR for PFS in TROP2-positive nonsquamous patients Primary

Hazard Ratio for Progression-Free Survival assessed by blinded independent central review (BICR) in the prespecified TROP2 biomarker-positive nonsquamous subgroup. This is the primary biomarker-enriched endpoint and the one most likely to show the largest treatment effect if TROP2 expression drives Dato-DXd activity. A Hazard Ratio below 1.0 favours the Dato-DXd arm.

Prediction range: 0.3 – 1.1 Hazard Ratio
NCT05687266HR for OS in TROP2-positive nonsquamous patientsPrimary

Hazard Ratio for Overall Survival in the prespecified TROP2 biomarker-positive nonsquamous subgroup. OS in this enriched population is the highest-bar regulatory endpoint and the result most likely to determine whether Dato-DXd can claim superiority over pembrolizumab plus chemotherapy in biomarker-selected first-line NSCLC. A Hazard Ratio below 1.0 favours the Dato-DXd arm.

Prediction range: 0.4 – 1.2 Hazard Ratio
NCT05687266HR for PFS in nonsquamous ITT population

Hazard Ratio for Progression-Free Survival assessed by blinded independent central review (BICR) in the prespecified TROP2 biomarker-positive nonsquamous subgroup. This is the primary biomarker-enriched endpoint and the one most likely to show the largest treatment effect if TROP2 expression drives Dato-DXd activity. A Hazard Ratio below 1.0 favours the Dato-DXd arm.

Prediction range: 0.3 – 1.2 Hazard Ratio
NCT05687266HR for OS in nonsquamous ITT population

Hazard Ratio for Overall Survival across the full nonsquamous intent-to-treat population. The relationship between this result and the TROP2-positive OS HR is the central biomarker question of the trial — a large divergence between the two would support a biomarker-selected label, while convergence would support broader use. A Hazard Ratio below 1.0 favours the Dato-DXd arm.

Prediction range: 0.3 – 1.2 Hazard Ratio

Key Facts

Study type
INTERVENTIONAL
Conditions
NSCLC
Interventions
Datopotamab deruxtecan, Durvalumab, Carboplatin, Pembrolizumab
Enrollment
1,350 participants
Primary completion
Nov 2027
Study completion
Nov 2027
First posted
Jan 2023
Last updated
Apr 2026

Primary Endpoints (CT.gov)

Progression-Free Survival (PFS) by blinded independent central review (BICR) in the non-squamous TROP2 biomarker positive population

Time frame: Approximately 3 years

Overall Survival (OS) in the non-squamous TROP2 biomarker positive population

Time frame: Approximately 5 years

PFS by BICR in the non-squamous population

Time frame: Approximately 3 years

OS in the non-squamous population

Time frame: Approximately 5 years

Secondary Endpoints

PFS by BICR in ITT and TROP2 biomarker-defined populations

OS in ITT and TROP2 biomarker-defined populations

Objective Response Rate (ORR) in ITT, non-squamous and TROP2 biomarker-defined populations

Eligibility Criteria

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 exc…

Read full criteria on CT.gov →

✦ Analyst Commentary

Expert commentary on why this trial matters and what to watch for.

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Source

Open on ClinicalTrials.gov

Related Program

Datroway (datopotamab deruxtecan)

AstraZeneca

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