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

Study identifier:D7632C00001

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:2023-505077-32-00

Will Be Recruiting

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)

Medical condition

Non-small Cell Lung Cancer

Phase

Phase 3

Healthy volunteers

Study drug

Datopotamab Deruxtecan, Rilvegostomig, Pembrolizumab

Sex

All

Estimated Enrollment

675

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 26 Apr 2024

Estimated Primary Completion Date: 24 May 2030

Estimated Study Completion Date: 24 May 2030

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2024 by AstraZeneca

Collaborators

Daiichi Sankyo

Inclusion and exclusion 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 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

No locations available

Arms	Assigned Interventions
Experimental: Arm 1: Dato-DXd in Combination With Rilvegostomig 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.	Drug: Datopotamab Deruxtecan Datopotamab Deruxtecan IV (intravenous) Other Name: Dato-DXd Drug: Rilvegostomig Rilvegostomig IV (intravenous) Other Name: AZD2936
Experimental: Arm 2: Rilvegostomig Monotherapy 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.	Drug: Rilvegostomig Rilvegostomig IV (intravenous) Other Name: AZD2936
Active Comparator: Arm 3: Pembrolizumab Monotherapy Participants in the pembrolizumab group will receive pembrolizumab as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.	Drug: Pembrolizumab Pembrolizumab IV (intravenous) Other Name: KEYTRUDA

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Suresh S. Ramalingam

Emory University, Atlanta, Georgia, United States of America.