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)

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Goal: To compare the efficacy and safety of ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy as first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC).

Patients: Adult patients (≥18 years) with stage IV squamous or non-squamous NSCLC, ECOG 0 or 1, no prior systemic therapy for metastatic disease, and absence of actionable oncogenic mutations (EGFR, ALK, ROS1, BRAF V600E) or small cell carcinoma. Patients must have at least one measurable noncerebral lesion and available PD-L1 Tumor Proportion Score, but enrollment is irrespective of PD-L1 status.

Design: Randomized, double-blind, active-controlled, multiregional phase 3 trial.

Treatments: One arm receives ivonescimab in combination with chemotherapy. Ivonescimab is a first-in-class tetravalent bispecific antibody targeting both PD-1 and VEGF, aiming to block angiogenesis and reverse immunosuppression. Previous studies show it improves progression-free survival and objective response rates compared to pembrolizumab in PD-L1-positive NSCLC, with a manageable safety profile and approval in China for certain indications. The comparator arm receives pembrolizumab with chemotherapy, the current standard first-line immunotherapy regimen for metastatic NSCLC without known driver mutations.

Outcomes: Co-primary endpoints are overall survival and progression-free survival by investigator assessment using RECIST 1.1. Key secondary outcomes include objective response rate and safety, including incidence and severity of adverse events and laboratory abnormalities.

Burden on patient: The trial is phase 3, double-blind, and uses standard chemotherapy and immunotherapy regimens, so burden is typical for first-line metastatic NSCLC trials. Required assessments likely mirror standard of care, with regular imaging and routine labs per protocol. No additional or unusual invasive procedures such as mandatory fresh biopsies or frequent pharmacokinetic sampling are described, making the patient burden low to moderate and in line with current clinical practice.

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London, Ontario, N6A5W9, Canada

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Ottawa, Ontario, K1H8L6, Canada

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Regina, Saskatchewan, S4T7T1, Canada

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Changsha, 410013, China

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Jiaxing, 330029, China

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Hubei, 434000, China

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Henan, 450003, China

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Fuzhou, 350014, China

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Beijing, 101149, China

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Beijing, 100044, China

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Beijing, 100000, China

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Yunnan, 650107, China

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Taizhou, 31700, China

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Shanghai, 200437, China

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Shanghai, 200032, China

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Shanghai, 200031, China

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Marseille, 13915, France

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Le Mans, 72000, France

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Villejuif, 94800, France

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Tours, 37044, France

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Créteil, 94010, France

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Caen, 14059, France

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Caen, 14033, France

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Quimper, 29107, France

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Montpellier, 34295, France

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Rennes, 35033, France

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Paris, 75000, France

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Saint-Herblain, 44805, France

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Pierre-Bénite, 69495, France

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Strasbourg, 67033, France

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Brest, 29200, France

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Giesen, 35392, Germany

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Luebeck, 23538, Germany

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Kempten, 87435, Germany

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Jena, 07747, Germany

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Heidelberg, 69126, Germany

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Gauting, 82131, Germany

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Frankfurt, 60488, Germany

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Esslingen, 73730, Germany

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Athens, 11526, Greece

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Athens, 11527, Greece

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Athens, 11528, Greece

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Athens, 15562, Greece

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Athens, 57010, Greece

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Patra, 26443, Greece

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Patra, 26504, Greece

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Thessaloníki, 54622, Greece

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Lucca, 55100, Italy

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Monza, 20900, Italy

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Peschiera Del Garda, 37019, Italy

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Verona, 37134, Italy

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Fukuoka, 810-8563, Japan

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Hiroshima, 734-8551, Japan

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Hokkaido, 003-0804, Japan

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Miyagi, 981-0914, Japan

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Okayama, 700-8558, Japan

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Osaka, 569-8686, Japan

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Osaka, 573-1191, Japan

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Tokyo, 104-0045, Japan

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Yamaguchi, 755-0241, Japan

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Guadalajara, 44670, Mexico

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Monterrey, 64060, Mexico

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Poznań, 60-693, Poland

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Łódź, 90-302, Poland

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Kragujevac, 34000, Serbia

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Belgrade, 11000, Serbia

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Belgrade, 11040, Serbia

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Belgrade, 11080, Serbia

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Kamenica, 21204, Serbia

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Niš, 18000, Serbia

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Lugo, 27003, Spain

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Jaén, 23007, Spain

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Girona, 17007, Spain

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Barcelona, 08107, Spain

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Barcelona, 08035, Spain

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Barcelona, 08028, Spain

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Badalona, 08916, Spain

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Badajoz, 06080, Spain

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Vigo, 36312, Spain

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Valencia, 46206, Spain

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Valencia, 46010, Spain

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Sevilla, 41013, Spain

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Pamplona, 31008, Spain

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Madrid, 28046, Spain

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Madrid, 28040, Spain

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Manchester, M20 4BX, United Kingdom

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London, EC1A 7BE, United Kingdom

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Little Rock, Arkansas, 72205, United States

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Santa Rosa, California, 95403, United States

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Santa Monica, California, 90404, United States

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Plantation, Florida, 33322, United States

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Pembroke Pines, Florida, 33028, United States

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Ocala, Florida, 34474, United States

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Jacksonville, Florida, 32256, United States

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Peoria, Illinois, 61615, United States

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Burlington, Massachusetts, 01805, United States

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Detroit, Michigan, 48202, United States

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Billings, Montana, 59102, United States

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New York, New York, 10029, United States

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New York, New York, 10065, United States

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Chapel Hill, North Carolina, 27514, United States

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Charlotte, North Carolina, 28204, United States

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Cleveland, Ohio, 44195, United States

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Cincinnati, Ohio, 45242, United States

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Cleveland, Ohio, 44106, United States

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Eugene, Oregon, 97401, United States

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Charleston, South Carolina, 29425, United States

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Greenville, South Carolina, 29605, United States

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Nashville, Tennessee, 37203, United States

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Tyler, Texas, 75702, United States

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Austin, Texas, 78745, United States

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Dallas, Texas, 75246, United States

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MD Anderson Cancer Center

Houston, Texas, 77030, United States

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San Antonio, Texas, 78216, United States

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Reston, Virginia, 20190, United States

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Norfolk, Virginia, 23502, United States

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Spokane, Washington, 99202, United States

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Seattle, Washington, 98103, United States

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Madison, Wisconsin, 53792, United States

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