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First-line treatment for metastatic non-small cell lung cancer with Ivonescimab

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)

Phase 3 Interventional Summit Therapeutics · NCT05899608

This study is testing if a new treatment called Ivonescimab, used with chemotherapy, can help people with advanced lung cancer live longer and feel better compared to a standard treatment.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment1600 (estimated)
Ages18 Years and up
SexAll
SponsorSummit Therapeutics Industry-sponsored
Drugs / interventionsIvonescimab, Pembrolizumab, Chemotherapy
Locations253 sites (Phoenix, Arizona and 252 other locations)
Trial IDNCT05899608 on ClinicalTrials.gov

What this trial studies

This Phase 3 clinical trial evaluates the effectiveness of Ivonescimab combined with chemotherapy compared to Pembrolizumab combined with chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC). The study is randomized and double-blind, focusing on overall survival and progression-free survival as primary endpoints, with secondary endpoints assessing response and safety. Participants must have confirmed metastatic NSCLC and meet specific eligibility criteria, including performance status and measurable lesions.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with metastatic NSCLC who have not received prior systemic treatment.

Not a fit: Patients with small cell lung carcinoma or known actionable genomic alterations that have approved first-line therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve survival rates and quality of life for patients with metastatic non-small cell lung cancer.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches in treating metastatic NSCLC, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Phoenix, Arizona and 252 other locations

+203 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Non-Small Cell Lung Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.