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)

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Investigational drug late phase More information Active drug More information Low burden on patient More information

Trial Details

Sponsor: Summit Therapeutics (industry)

Phase: 3

Start date: Oct. 26, 2023

Planned enrollment: 1080

Trial ID: NCT05899608
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More trial details at ClinicalTrials.gov More info

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Investigational Drug AI Analysis

chevron Show for: Ivonescimab (AK112/SMT112)

TrialFetch AI Analysis

Goal: Determine whether first-line ivonescimab plus chemotherapy improves survival compared with pembrolizumab plus chemotherapy in metastatic non-small cell lung cancer (NSCLC).

Patients: Adults with previously untreated stage IV squamous or nonsquamous NSCLC, ECOG performance status 0–1, a recorded PD-L1 tumor proportion score regardless of expression level, and at least one measurable noncerebral lesion. Patients with actionable alterations for which approved first-line therapies are available, including EGFR, ALK, ROS1, or BRAF V600E, are excluded.

Design: Randomized, double-blind, multiregional comparison of two first-line treatment regimens.

Treatments: Patients receive ivonescimab plus chemotherapy or pembrolizumab plus chemotherapy. Ivonescimab is an investigational bispecific antibody targeting PD-1 and VEGF-A, intended to inhibit immune suppression and tumor angiogenesis. In other phase 3 NSCLC populations, ivonescimab-based regimens improved progression-free survival over their respective comparators; those results do not establish benefit for this trial’s population or regimen. Pembrolizumab is an established PD-1 inhibitor used with chemotherapy as first-line treatment for metastatic NSCLC.

Outcomes: Primary endpoints are overall survival in the intention-to-treat population and investigator-assessed progression-free survival by RECIST 1.1. Secondary assessments include response and safety, including adverse events and clinically significant laboratory abnormalities.

Burden on patient: Moderate: both arms require clinic visits for injected immunotherapy and chemotherapy, along with imaging, laboratory monitoring, and follow-up typical of first-line metastatic NSCLC treatment. PD-L1 assessment and, for nonsquamous disease, driver testing are required before randomization. No mandatory research biopsy or intensive pharmacokinetic sampling is specified.

Last updated: Sep 2026

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Caution: ClinicalTrials.gov appears to have newer eligibility criteria than the version saved here. Review the current criteria in ClinicalTrials.gov.

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BRCR Medical Center Inc.

Tamarac, Florida, 33321, United States

No email / No phone

Status: Recruiting

BioResearch Partner- Hialeah Hospital

Hialeah, Florida, 33013, United States

No email / No phone

Status: Recruiting

Cancer Care of Brevard

Palm Bay, Florida, 32901, United States

No email / No phone

Status: Recruiting

Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

No email / No phone

Status: Recruiting

Exigent Network

Petersburg, Florida, 33709, United States

No email / No phone

Status: Recruiting

Florida Cancer Specialists & Research Institute (FCS) - North

St. Petersburg, Florida, 33705, United States

No email / No phone

Status: Recruiting

Florida Cancer Specialists & Research Institute (FCS)-East

Fort Myers, Florida, 33901, United States

No email / No phone

Status: Recruiting

Florida Cancer Specialists & Research Institute (FCS)-South

West Palm Beach, Florida, 33401, United States

No email / No phone

Status: Recruiting

Mayo Clinic

Jacksonville, Florida, 32224, United States

No email / No phone

Status: Recruiting

Memorial Cancer Institute

Pembroke Pines, Florida, 33028, United States

No email / No phone

Status: Recruiting

Ocala Oncology

Ocala, Florida, 34474, United States

No email / No phone

Status: Recruiting

Illinois Cancer Care

Peoria, Illinois, 61615, United States

No email / No phone

Status: Recruiting

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

No email / No phone

Status: Recruiting

Baptist Health

Lexington, Kentucky, 40503, United States

No email / No phone

Status: Recruiting

Ascension Saint Agnes Hospital

Baltimore, Maryland, 21229, United States

No email / No phone

Status: Recruiting

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21187, United States

No email / No phone

Status: Recruiting

Lahey Hospital

Burlington, Massachusetts, 01805, United States

No email / No phone

Status: Recruiting

Henry Ford Hospital

Detroit, Michigan, 48202, United States

No email / No phone

Status: Recruiting

Karmanos Cancer Insitute

Detroit, Michigan, 48201, United States

No email / No phone

Status: Recruiting

Trinity Health

Ann Arbor, Michigan, 48197, United States

No email / No phone

Status: Recruiting

University of Michigan

Ann Arbor, Michigan, 48109, United States

No email / No phone

Status: Recruiting

Mayo Clinic

Rochester, Minnesota, 55905, United States

No email / No phone

Status: Recruiting

Park Nicollet Institute

Saint Paul, Minnesota, 55101, United States

No email / No phone

Status: Recruiting

American Oncology Partners, PA

Kansas City, Missouri, 64132, United States

No email / No phone

Status: Recruiting

Washington University St.Louis

St Louis, Missouri, 63110, United States

No email / No phone

Status: Recruiting

St. Vincent Cancer Center

Billings, Montana, 59102, United States

No email / No phone

Status: Recruiting

University of Nebraska Medical Center (UNMC)

Omaha, Nebraska, 68105, United States

No email / No phone

Status: Recruiting

Memorial Sloan Kettering

New York, New York, 10065, United States

No email / No phone

Status: Recruiting

Mount Sinai

New York, New York, 10029, United States

No email / No phone

Status: Recruiting

Levine Center

Charlotte, North Carolina, 28204, United States

No email / No phone

Status: Recruiting

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

No email / No phone

Status: Recruiting

Cleveland Clinic

Cleveland, Ohio, 44195, United States

No email / No phone

Status: Recruiting

Oncology Hematology Care (OHC), Inc

Cincinnati, Ohio, 45242, United States

No email / No phone

Status: Recruiting

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

No email / No phone

Status: Recruiting

Willamette Valley Cancer Institute and Research Center (WVCI)

Eugene, Oregon, 97401, United States

No email / No phone

Status: Recruiting

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

No email / No phone

Status: Recruiting

Prisma Health-Upstate

Greenville, South Carolina, 29605, United States

No email / No phone

Status: Recruiting

SCRI-Nashville

Nashville, Tennessee, 37203, United States

No email / No phone

Status: Recruiting

West Cancer Center

Memphis, Tennessee, 38138, United States

No email / No phone

Status: Recruiting

Houston Methodist Hospital

Houston, Texas, 77030, United States

No email / No phone

Status: Recruiting

MD Anderson Cancer Center

Houston, Texas, 77030, United States

[email protected] / 713-563-6096

Status: Recruiting

Texas Oncology- Austin

Austin, Texas, 78745, United States

No email / No phone

Status: Recruiting

Texas Oncology-Dallas

Dallas, Texas, 75246, United States

No email / No phone

Status: Recruiting

Texas Oncology-San Antonio

San Antonio, Texas, 78216, United States

No email / No phone

Status: Recruiting

Texas Oncology-Tyler

Tyler, Texas, 75702, United States

No email / No phone

Status: Recruiting

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

No email / No phone

Status: Recruiting

University of Texas at Tyler

Tyler, Texas, 75708, United States

No email / No phone

Status: Recruiting

Virginia Cancer

Reston, Virginia, 20190, United States

No email / No phone

Status: Recruiting

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

No email / No phone

Status: Recruiting

Cancer Care NW Centers

Spokane, Washington, 99202, United States

No email / No phone

Status: Recruiting

Swedish Cancer Institute

Seattle, Washington, 98103, United States

No email / No phone

Status: Recruiting

Carbone Cancer Center

Madison, Wisconsin, 53792, United States

No email / No phone

Status: Recruiting

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