Recruiting NCT06357533

Phase III, Open-label, Study of First-line Dato-DXd in Combination With Rilvegostomig for Advanced Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations

Phase III Interventional 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: Datopotamab Deruxtecan, Rilvegostomig, Pembrolizumab.
Who it may be relevant to: Registry conditions: Non-Small Cell Lung Cancer. Basic parameters: from 18 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, Austria, Belgium, Brazil +16
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, Randomised, Open-label, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Pembrolizumab Monotherapy for the First-line Treatment of Participants With Locally-advanced or Metastatic Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations (TROPION-Lung10)

Overview

The purpose of this study is to evaluate efficacy and safety of Dato-DXd in combination with rilvegostomig or rilvegostomig monotherapy compared with pembrolizumab monotherapy as a first line therapy in participants with locally advanced or metastatic non-squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.

Detailed description

This is a Phase III, randomized, open-label, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig monotherapy compared with Pembrolizumab monotherapy for the first-line treatment of participants with locally-advanced or metastatic non-squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.

Interventions

Drug Datopotamab Deruxtecan
Datopotamab Deruxtecan IV (intravenous)
Drug Rilvegostomig
Rilvegostomig IV (intravenous)
Drug Pembrolizumab
Pembrolizumab IV (intravenous)

Primary outcome measures

Progression-Free Survival (PFS) in TROP2 biomarker positive participants. [Time frame: Approximately 4 years]
Overall Survival (OS) in TROP2 biomarker positive participants. [Time frame: Approximately 6 years]

Secondary outcome measures (9)

Progression-Free Survival (PFS) in the FAS population. [Time frame: Approximately 4 years]
Overall Survival (OS) in the FAS population. [Time frame: Approximately 6 years]
Assessment of Objective Response Rate (ORR) by BICR in TROP2 biomarker positive and FAS populations [Time frame: Approximately 4 years]
Assessment of Duration of Response (DoR) by BICR in TROP2 biomarker positive and FAS populations [Time frame: Approximately 4 years]
Participant-reported lung cancer symptoms of NSCLC and participant-reported GHS/QOL in participants treated with Dato-DXd in combination with rilvegostomig relative to pembrolizumab. [Time frame: Approximately 6 years]
Participant-reported physical functioning in participants treated with Dato DXd in combination with rilvegostomig relative to pembrolizumab. [Time frame: Approximately 6 years]
Pharmacokinetics (PK) [Time frame: Approximately 6 years]
Immunogenicity [Time frame: Approximately 6 years]
Second Progression-Free Survival (PFS2). [Time frame: Approximately 6 years]

Eligibility criteria

Inclusion criteria

Histologically or cytologically documented non-squamous NSCLC.
Stage IIIB or IIIC or Stage IV metastatic NSCLC (according to Edition 8 of the AJCC staging manual) not amenable to curative surgery or definitive chemoradiation.
Absence of sensitising EGFR mutations, and ALK and ROS1 rearrangements, and absence of documented local test result for any other known genomic alteration for which there are locally approved and available targeted first-line therapies.
Must provide tumor sample to determine PD-L1 status, TROP2 status and other biomarkers.
Known tumour PD-L1 expression status defined as TC ≥ 50%
At least one lesion, not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline
ECOG performance status of 0 or 1
Adequate bone marrow reserve and organ function

Exclusion criteria

Prior systemic therapy for advanced/metastatic NSCLC.
Squamous cell histology, or predominantly squamous cell histology NSCLC; mixed small cell lung cancer; NSCLC histology, sarcomatoid variant.
History of another primary malignancy within 3 years
Active or prior documented autoimmune or inflammatory disorders (with exceptions)
Any evidence of severe or uncontrolled disease that makes it undesirable for the participant to participate in the study or that would jeopardies compliance with the protocol.
Has clinically significant third-space fluid retention (for example pleural effusion) and is not amenable for repeated drainage.
History of any ILD/pneumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, has current or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
Has significant pulmonary function compromise, as determined by the investigator
Spinal cord compression, or brain metastases unless participant treated and no longer symptomatic, radiologically stable, and who require no treatment with corticosteroids or anticonvulsants.
History of leptomeningeal carcinomatosis
Known clinically significant corneal disease
Active infection with TB, HBV, HCV, Hepatitis A, or known HIV infection that is not well controlled
History of active primary immunodeficiency

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: Single blind
Primary purpose: Treatment