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 (TROPION-Lung10)

AstraZeneca

Status and phase: Enrolling; Phase 3

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: Datopotamab Deruxtecan; Drug: Rilvegostomig; Drug: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06357533

D7632C00001

Details and patient eligibility

About

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.

Full description

This is a Phase III, randomized, 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.

Enrollment: 675 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 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 within 7 days before the first dose of study intervention

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 systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease.
• Has clinically significant third-space fluid retention (for example pleural effusion) and is not amenable for repeated drainage.
• 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
• Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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675 participants in 3 patient groups

Arm 1: Dato-DXd in Combination With Rilvegostomig

Experimental group

Description:

Participants in the Dato-DXd in combination with Rilvegostomig group will receive Dato-DXd plus rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Treatment:

Drug: Rilvegostomig

Drug: Datopotamab Deruxtecan

Arm 2: Rilvegostomig Monotherapy

Experimental group

Description:

Participants in the rilvegostomig monotherapy group will receive rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Treatment:

Drug: Rilvegostomig

Arm 3: Pembrolizumab Monotherapy

Active Comparator group

Description:

Participants in the pembrolizumab group will receive pembrolizumab as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Treatment:

Drug: Pembrolizumab