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)

JRCT ID: jRCT2061240051

Registered date:03/09/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Metastatic Non-small Cell Lung Cancer
• Date of first enrollment: 17/10/2024
• Target sample size: 77
• Countries of recruitment: Australia,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,China,Japan,France,Japan,Germany,Japan,Greece,Japan,India,Japan,Israel,Japan,Italy,Japan,Korea,Japan,Malaysia,Japan,Philippines,Japan,Poland,Japan,Singapore,Japan,Spain,Japan,Taiwan,Japan,Thailand,Japan,United Kingdom,Japan,United States,Japan,Vietnam,Japan
• Study type: Interventional
• Intervention(s): Pparticipants will be randomized in a 1:1:1 ratio to receive either Dato DXd combined with osimertinib, Dato-DXd monotherapy, or chemotherapy.

Outcome(s)

• Primary Outcome: PFS is defined as the time from randomization to Blinded Independent Central Review (BICR)-assessed progression using RECIST v1.1 or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinical progression.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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.

Exclude 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.

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT06417814