A Randomized, Double-blinded, Multiregional Phase 3 Study of Ivonescimab Versus Pembrolizumab for the First-line Treatment of Metastatic Non-small Cell Lung Cancer in Patients Whose Tumors Demonstrate High PD-L1 Expression

Eligibility: Inclusion Criteria
  •   * Age >= 18 years old at the time of enrollment
  •   * Eastern Cooperative Oncology Group (ECOG) performance status score of 0 - 1
  •   * Expected life expectancy >= 3 months
  •   * Metastatic (Stage IV) NSCLC
  •   * Histologically or cytologically confirmed squamous or non-squamous NSCLC
  •   * Tumor demonstrates high PD-L1 expression ( TPS>50%) based on a 22C3 immunohistochemistry ( IHC) clinical assay approved / cleared by local health authorities.
  •   * At least one measurable noncerebral lesion according to RECIST 1.1
  •   * No prior systemic treatment for metastatic NSCLC.
Exclusion Criteria
  •   * Histologic or cytopathologic evidence of the presence of small cell lung carcinoma for which first-line approved therapies are indicated. For patients with non-squamous histology, actionable driver mutation testing results are required before randomization.
  •   * Has received any prior therapy for NSCLC in the metastatic setting.
  •   * Concurrent enrollment in another clinical study, unless patient is enrolled in a non-interventional clinical study or is completing survival follow -up.
  •   * Known actionable genomic alterations for which first-line approved therapies are indicated
  •   * Symptomatic CNS metastases, CNS metastasis >= 1.5 cm, CNS radiation within 7 days prior to randomization, potential need for CNS radiation within the first cycle, or leptomeningeal disease
  •   * Other prior malignancy (including previously treated NSCLC) unless the patient has undergone curative therapy with no evidence of recurrence of the disease for 3 years prior to randomization
  •   * Active autoimmune or lung disease requiring systemic therapy
  •   * Has pre-existing peripheral neuropathy that is >= Grade 2 by CTCAE version 5
  •   * Severe infection within 4 weeks prior to randomization
  •   * Major surgical procedures or serious trauma within 4 weeks prior to randomization
  •   * History of noninfectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease