Sensitizing and T790M mutant EGFR tyrosine kinase inhibition

The key inclusion criteria are^1,2-

• Age ≥18 years (if the legal age of consent is >18 years, then follow local regulatory requirements)
• Histologically documented nonsquamous NSCLC:
  • Must have evidence of documented pre-existing EGFRm information (EGFRm known to be associated with (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^a.
• 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 at baseline and can be accurately measured at baseline.
• WHO/ECOG PS 0 or 1.
• Adequate bone marrow reserve and organ function within 7 days before randomization.
• No more than 28 days off osimertinib prior to randomization
• Tumor biopsy or archival tissue for retrospective evaluation of exploratory biomarkers

^aPer the IASLC Cancer Staging Manual in Thoracic Oncology version 9

References:

1. Study NCT06417814. ClinicalTrials.gov website.
2. Tan DS, et al. Ther Adv Med Oncol. 2025;17:17588359251385410.

The key exclusion criteria are^1,2-

• 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 (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 HIV infection that is not well controlled.