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 - TROPION-Lung15

Study identifier:D516KC00001

ClinicalTrials.gov identifier:NCT06417814

EudraCT identifier:N/A

CTIS identifier:N/A

Will Be Recruiting

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)

Medical condition

metastatic non-small cell lung cancer

Phase

Phase 3

Healthy volunteers

Study drug

Dato-DXd, Osimertinib, Pemetrexed, Carboplatin, Cisplatin

Sex

All

Estimated Enrollment

630

Study type

Interventional

Age

18 Years - n/a

Date

Study Start Date: 12 Aug 2024

Estimated Primary Completion Date: 08 Sept 2026

Estimated Study Completion Date: 08 Feb 2028

Study design

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

Verification:

Verified 01 Jun 2024 by AstraZeneca

Collaborators

Daiichi Sankyo

Inclusion and exclusion 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 IV antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections.
- Has known human immunodeficiency virus (HIV) infection that is not well controlled.

No locations available

Arms	Assigned Interventions
Experimental: Group 1: Dato-DXd + Osimertinib Combination Therapy Participants will receive Dato-DXd 6 mg/kg as IV infusion Q3W on Day 1 of every 21-day cycle, and osimertinib 80 milligrams (mg) once daily (QD) orally, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met.	Drug: Dato-DXd Dato-DXd will be administered as IV infusion. Other Name: DS-1062a Drug: Osimertinib Osimertinib will be administered orally. Other Name: Tagrisso Other Name: AZD9291
Experimental: Group 2: Dato-DXd Monotherapy Participants will receive Dato-DXd 6 milligrams per kilogram (mg/kg) as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of every 21-day cycle, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met.	Drug: Dato-DXd Dato-DXd will be administered as IV infusion. Other Name: DS-1062a
Experimental: Group 3: Platinum-based Doublet Chemotherapy Participants will receive pemetrexed 500 milligrams per meter square (mg/m2) in combination with carboplatin (AUC5) or cisplatin 75 mg/m2 as IV infusion Q3W for 4 cycles followed by pemetrexed maintenance 500 mg/m2 as IV infusion Q3W, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or another discontinuation criterion is met.	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.

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]