Sensitizing and T790M mutant EGFR tyrosine kinase inhibition

The key inclusion criteria are-

• Age ≥18 years (if the legal age of consent is >18 years, then follow local regulatory requirements)
• Histologically documented nonsquamous NSCLC:
  • The tumor harbors 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations
• Participants must not have received prior EGFR TKIs or other systemic therapy for Stage IIIB, IIIC or IV NSCLC^a
• Provision of an unstained, archival tumor tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status
• Measurable disease per RECIST v1.1
• ECOG PS of 0–1 at screening
• Life expectancy ≥3 months
• Adequate bone marrow function within 7 days before randomization

^aClassification based on the American Joint Committee on Cancer, 8th edition

Reference:

Study NCT06350097. ClinicalTrials.gov website

The key exclusion criteria are-

• Evidence of diseases, history of allogenic organ transplant, and/or substance abuse which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol
• Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of osimertinib
• History of another primary malignancy
• Spinal cord compression and unstable brain metastases
• Clinically significant corneal disease
• Active or uncontrolled infection, including hepatitis B/C virus, or HIV
• Uncontrolled infection requiring IV antibiotics, antivirals or antifungals, suspected, or inability to rule-out infection
• Resting ECG with clinically abnormal findings
• Uncontrolled or significant cardiac disease
• Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
• Has severe pulmonary function compromise
• Prior exposure to any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase I, TROP2-directed therapy
• Known history of severe hypersensitivity reactions to either Dato-DXd and osimertinib or any excipients of Dato-DXd and osimertinib or drugs with a similar chemical structure or class to DXd and osimertinib