Clinical Study of Ivonescimab for First-line Treatment of Metastatic NSCLC Patients

This study consists of two distinct NSCLC histology cohorts: squamous (N=600) and non-squamous (N=1000), approximately 1600 patients in total. Within each cohort, subjects are randomized in a 1:1 ratio into one of two treatment groups, receiving either ivonescimab or pembrolizumab combined with platinum-doublet chemotherapy. The two histology cohorts will be analyzed independently

• Ivonescimab Injection (Biological): Subject will receive ivonescimab and chemotherapy as an IV injection
• Pembrolizumab Injection (Biological): Subject will receive pembrolizumab and chemotherapy as an IV injection

Primary outcomes

• Overall Survival (OS) [approximately 4 years]: Overall Survival (OS) in the ITT population
• Progression Free Survival (PFS) [approximately 3 years]: Progression Free Survival (PFS) assessed by investigator based on RECIST V1.1

Secondary outcomes

• Adverse Event (AE) [From the subject signs the ICF to 30 days (AE) and 90 days (SAE related to ivonescimab/pembrolizumab ) after the last dose of study treatment or initiation of other anticancer therapy, whichever occurs first, up to 2 years.]: incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory test results

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age ≥ 18 years old at the time of enrollment
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
* Expected life expectancy ≥ 3 months
* Metastatic (Stage IV) NSCLC
* Histologically or cytologically confirmed squamous or non-squamous NSCLC
* Recorded measurement of the Tumor Proportion Score (TPS) or Tumor Cells (TC) for PD-L1 expression, irrespective of the PD-L1 expression, prior to randomization
* 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
* Known actionable genomic alterations (EGFR, ALK, ROS1, and BRAF V600E) or genes for which first-line approved therapies are available.

  * For non-squamous histology patients, actionable driver mutation testing results are required before randomization.
* Has received any prior therapy for NSCLC in the metastatic setting
* Tumor invasion, encasement of organs (e.g. pericardium, heart, trachea, esophagus, central bronchi), or major blood vessels (e.g aorta, central veins), if poses a significant increased risk of bleeding.

160 more sites not listed.

• Indu Lal, Study director, Summit Therapeutics, Inc.