This is a Phase II, single-arm, multicenter trial for patients with metastatic non-small cell lung cancer who have brain metastases and no known actionable mutations. Eligible patients will receive a combination of Datopotamab-deruxtecan, Carboplatin, and Pembrolizumab every three weeks for four cycles, followed by maintenance therapy with Datopotamab-deruxtecan and Pembrolizumab until disease progression or intolerable toxicity. Patients with intracranial progression but no systemic progression may receive stereotactic radiosurgery and continue treatment based on the investigator's decision.
Documented negative test results for EGFR and ALK actionable genomic alterations by local test;
No known actionable genomic alterations in ROS1, NTRK, RET, HER2, or MET.
No prior systemic therapy for advanced or metastatic NSCLC. Patients who received chemotherapy or immunotherapy for localized or locally advanced NSCLC are eligible if progression occurred at least 6 months after the last dose of systemic treatment.
Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible.
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to inclusion.
Has received prior radiotherapy to the brain within 2 weeks of the start of therapy, or received radiotherapy to the chest within 4 weeks of start of therapy, or that have ongoing radiation-related toxicities requiring corticosteroid.
Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
Single group
Pembrolizumab
DrugPembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2).
Datopotamab deruxtecan
DrugDatopotamab deruxtecan (Dato-DXd) is a novel antibody-drug conjugate (ADC) composed of a humanized anti-TROP2 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload and a cleavable linker.
Carboplatin
DrugCarboplatin is a platinum compound chemotherapy used to treat lung cancer with a known safety profile. For more details on specific indications refer to the approved product label.
Confirmed Intracranial Objective Response Rate (iORR) as Measured by the RANO-BM Criteria
The intracranial objective response rate (iORR) is defined as the proportion of patients achieving a complete response (CR) or partial response (PR) according to the RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) criteria, as assessed by central review. The best overall CNS (central nervous system) response is determined based on a composite assessment of radiographical CNS target and non-target lesion responses, corticosteroid use, and clinical status.
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Latin American Cooperative Oncology Group
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
AstraZeneca
Collaborator
