Title
A Randomized, Double-blind, Multiregional Phase 3 Study of Ivonescimab Combined with Chemotherapy Versus Pembrolizumab Combined with Chemotherapy for the First-line Treatment of Metastatic Non-small Cell Lung Cancer (HARMONi-3)

Description
A Randomized, Controlled, Multiregional Phase 3 Study of Ivonescimab Combined With Chemotherapy Versus Pembrolizumab Combined With Chemotherapy for the First-line Treatment of Metastatic Squamous Non-small Cell Lung Cancer (HARMONi-3)

Objective
Primary Objective: To compare OS between ivonescimab combined with carboplatin and paclitaxel or nabpaclitaxel versus pembrolizumab combined with carboplatin and paclitaxel or nabpaclitaxel

Secondary Objectives:
1) To compare investigator assessed PFS based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 between ivonescimab combined with carboplatin and paclitaxel or nab-paclitaxel and pembrolizumab combined with carboplatin and paclitaxel or nabpaclitaxel
2) To compare the objective response rate (ORR) and duration of response (DoR) between
ivonescimab combined with carboplatin and paclitaxel or nab-paclitaxel versus pembrolizumab combined with carboplatin and paclitaxel or nab-paclitaxel, as assessed by investigator, based on RECIST v1.1
3) To evaluate the safety and tolerability of ivonescimab in combination with carboplatin and paclitaxel or nab-paclitaxel and compare to pembrolizumab combined with carboplatin and paclitaxel or nab-paclitaxel
4) To evaluate the pharmacokinetic profile of ivonescimab in combination with carboplatin and paclitaxel or nab-paclitaxel
5) To evaluate the immunogenicity of ivonescimab

Exploratory Objectives:
1) To explore potential tumor specific biomarkers in tumor tissue and peripheral blood samples
2) To evaluate central nervous system (CNS) metastases response in patients with CNS
metastasis at baseline
3) To evaluate health-related quality-of-life (HRQoL) measures of ivonescimab combined with carboplatin and paclitaxel or nab-paclitaxel versus pembrolizumab combined with carboplatin and paclitaxel or nab-paclitaxel

Treatment This is a Phase 3 Randomized, Controlled, Multiregional Study of Ivonescimab Combined with Chemotherapy Versus Pembrolizumab Combined with Chemotherapy for the First-line Treatment of Metastatic Squamous Non-small Cell Lung Cancer. The primary endpoint is overall survival and key secondary endpoints include progression free survival. response and safety.

Key Eligibility 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 NSCLC

Tumor Proportion Score (TPS) with PD-L1 expression percent

At least one measurable noncerebral lesion according to RECIST 1.1

No prior systemic treatment for metastatic NSCLC

Applicable Disease Sites
Lung

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital