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

Launched by ASTRAZENECA · May 13, 2024

Keywords

ClinConnect Summary

This clinical trial is investigating the effectiveness and safety of a new treatment called Dato-DXd, either on its own or combined with another drug called osimertinib, for patients with advanced non-small cell lung cancer (NSCLC) that has spread to other parts of the body. The researchers want to see how long patients can live without their cancer worsening compared to those receiving standard chemotherapy. The study is currently looking for participants and aims to help find better treatment options for people with specific types of EGFR mutations, which are changes in a gene that can affect how cancer grows.

To be eligible for this trial, participants should have a confirmed diagnosis of non-squamous NSCLC and have previously received treatment with osimertinib. Other key requirements include having limited prior treatments with other targeted therapies and being able to measure at least one tumor that hasn't been treated with radiation. Participants will be monitored closely during the trial, and the goal is to provide them with new treatment options that may improve their outcomes. If you or a loved one meets these criteria, this trial could be an opportunity to contribute to important research while exploring potential new therapies.

Gender

ALL

Eligibility 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.