Recruiting NCT06417814

A Study to Investigate the Efficacy and Safety of Dato-DXd With or Without Osimertinib Compared With Platinum Based Doublet Chemotherapy in Participants With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Phase III Interventional Metastatic Non-small Cell Lung Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Dato-DXd, Osimertinib, Pemetrexed, Carboplatin.
Who it may be relevant to: Registry conditions: Metastatic Non-small Cell Lung Cancer. Basic parameters: 18 years — 130 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, Belgium, Brazil, Canada +22
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

A Phase III, Open-label, Sponsor-blind, Randomized Study of Dato-DXd With or Without Osimertinib Versus Platinum-based Doublet Chemotherapy for Participants With EGFR-mutated Locally Advanced or Metastatic Non-small Cell Lung Cancer Whose Disease Has Progressed on Prior Osimertinib Treatment (TROPION-Lung15)

Overview

This study will assess the effect of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in terms of progression-free survival (PFS).

Detailed description

This is a Phase III, open-label, 3-arm, multicenter study assessing the effects of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in participants with epidermal growth factor receptor gene mutation (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on prior osimertinib treatment.

Participants will be randomized in a 1:1:1 ratio to one of the following intervention groups:

1. Dato-DXd + osimertinib combination therapy 2. Dato-DXd monotherapy 3. Platinum-based doublet chemotherapy

Participants will receive study intervention until Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) -defined radiological progression by the investigator, unacceptable toxicity, or other discontinuation criterion is met.

After study intervention discontinuation, all participants will undergo an end of treatment (EoT) visit within 35 days of discontinuation and will be followed up for safety assessments 28 (+ 7) days after their last dose of study intervention.

Interventions

Drug Dato-DXd
Dato-DXd will be administered as IV infusion.
Drug Osimertinib
Osimertinib will be administered orally.
Drug Pemetrexed
Pemetrexed will be administered as IV infusion.
Drug Carboplatin
Carboplatin will be administered as IV infusion.
Drug Cisplatin
Cisplatin will be administered as IV infusion.

Primary outcome measures

Progression free Survival (PFS) [Time frame: Up to 2.5 years]

Secondary outcome measures (12)

Overall Survival (OS) [Time frame: Up to 3.5 years]
Central Nervous System Progression-free Survival (CNS PFS) [Time frame: Up to 2.5 years]
Objective Response Rate (ORR) [Time frame: Up to 2.5 years]
Duration of Response (DoR) [Time frame: Up to 2.5 years]
Progression-free Survival-2 (PFS-2) [Time frame: Up to 3.5 years]
Objective Response Rate (ORR) Using CNS Modified RECIST v1.1 [Time frame: Up to 2.5 years]
Duration of Response (DoR) Using CNS Modified RECIST v1.1 [Time frame: Up to 2.5 years]
Time to Deterioration in Pulmonary Symptoms [Time frame: Up to 3.5 years]
Time to Deterioration in Physical Functioning [Time frame: Up to 3.5 years]
Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL) [Time frame: Up to 3.5 years]
Pharmacokinetics (PK) of Dato-DXd [Time frame: Up to 3.5 years]
Immunogenicity of Dato-DXd [Time frame: Up to 3.5 years]

Eligibility criteria

Inclusion criteria

Histologically or cytologically confirmed non-squamous NSCLC.
Must have evidence of documented pre-existing EGFRm information (EGFRm known to be associated with (epidermal growth factor receptor \[EGFR\] tyrosine kinase inhibitor \[TKis\] sensitivity \[Ex19del, L858R, G719X, S768I, or L861Q\], either alone or in combination with other EGFR mutations, which may include T790M).
Documented extra-cranial radiologic progression on prior osimertinib monotherapy (as most recent line of treatment) in the adjuvant, locally advanced, or metastatic setting.
Less than or equal to (<=2) prior lines of EGFR TKIs (osimertinib is the only permitted prior third generation EGFR TKI).
At least one lesion, not previously irradiated, that qualifies as a RECIST v1.1 TL at baseline and can be accurately measured at baseline.
World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Adequate bone marrow reserve and organ function within 7 days before randomization.

Exclusion criteria

Use of chemotherapy, vascular endothelial growth factor inhibitor, immunotherapy or any anti-cancer therapy in the metastatic setting. Platinum-based chemotherapy in non-metastatic setting within 12 months prior to randomization.
History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention.
Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease.
Has significant third-space fluid retention (example \[eg.\], ascites or pleural effusion) as judged by the investigator and is not amenable for required repeated drainage.
History of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids or drug-induced ILD, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
Unstable spinal cord compression and/or unstable brain metastases.
Participants with symptomatic brain metastases (including leptomeningeal involvement).
Clinically significant corneal disease.
Uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections. Use of systemic antibiotics within 14 days of randomization.
Has known human immunodeficiency virus (HIV) infection that is not well controlled.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Open label
Primary purpose: Treatment

Study locations

China · 38 centers

Research Site — Baoding
Research Site — Beijing
Research Site — Beijing
Research Site — Beijing
Research Site — Beijing
Research Site — Beijing
Research Site — Beijing
… and 31 more centers

United States · 34 centers

Research Site — Fayetteville
Research Site — Duarte
Research Site — Fountain Valley
Research Site — La Jolla
Research Site — Los Angeles
Research Site — San Diego
Research Site — Colorado Springs
Research Site — Fort Collins
… and 26 more centers

Japan · 24 centers