Phase III Study of AK112 for NSCLC Patients

NCT ID: NCT06396065

Last Updated: 2024-10-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-04

Study Completion Date

2025-12-31

Brief Summary

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A Randomized, Double-blind, Multi-center, Phase III Clinical Study of AK112 or Placebo Combined With Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Progressed on or Following Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment (HARMONi)

Detailed Description

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The trial will be performed as a randomized, Double-Blind, Multicenter trial to compare Ivonescimab (SMT112 /AK112) Plus Pemetrexed and Carboplatin to Placebo Plus Pemetrexed and Carboplatin in Patients with Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Harboring. Approximately 420 subjects will be randomized to two treatment arms at the ratio of 1:1. Each enrolled subject will receive an intravenous infusion of the Ivonescimab (SMT112 /AK112)/Placebo Plus Pemetrexed and Carboplatin (Q3W,up to 4 cycles) in treatment periods per the randomization schedule. Afterward, Ivonescimab (SMT112 /AK112)/ Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Conditions

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Non-Squamous Non-small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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AK112 in combination with Pemetrexed and Carboplatin

Subjects will receive AK112 Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles. Afterward, AK112 Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Group Type EXPERIMENTAL

AK112 Injection

Intervention Type DRUG

Subjects will receive AK112 Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles. Afterward, AK112 Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Placebo in combination with Pemetrexed and Carboplatin

Subjects will receive Placebo Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles in treatment periods per the randomization schedule. Afterward, Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Group Type ACTIVE_COMPARATOR

Placebo Injection

Intervention Type DRUG

Subjects will receive Placebo Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles in treatment periods per the randomization schedule. Afterward, Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Interventions

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AK112 Injection

Subjects will receive AK112 Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles. Afterward, AK112 Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Intervention Type DRUG

Placebo Injection

Subjects will receive Placebo Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles in treatment periods per the randomization schedule. Afterward, Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

Intervention Type DRUG

Other Intervention Names

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Pemetrexed Carboplatin Pemetrexed Carboplatin

Eligibility Criteria

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Inclusion Criteria

1. Ability to understand and voluntarily sign a written informed consent form (ICF), which must be signed before the specified study procedures required for the study are performed.
2. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent. (For patients from North America and Europe, there will be no upper age cutoff)
3. ECOG performance status score of 0 or 1.
4. Expected survival ≥3 months.
5. Histologically or cytology-confirmed, locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-squamous NSCLC (according to TNM staging of lung cancer, 8th edition) that cannot be completely resected by surgery and cannot receive radical concurrent/sequential chemoradiation.
6. EGFR activation mutations that are confirmed by tumor histology or cytology or blood test before enrollment (eg, exon 18 point mutations, exon 19 deletions, exon 20 point mutations, and exon 21 point mutations). Patients must provide a previous EGFR mutation test report, otherwise tumor tissue samples, peripheral blood samples, or pleural fluid samples will need to be collected for EGFR status testing prior to enrollment.
7. Prior treatment with EGFR TKI and treatment failure, meeting any of the following requirements: Progression after treatment with first- or second-generation EGFR TKI, and confirmation of absence of T790M mutation after progression (only for patients enrolled in China). Progression after treatment with a third-generation EGFR TKI (eg, osimertinib, ametinib, vometinib). Note, for North America and Europe patients only.
8. According to RECIST v1.1, there is at least 1 measurable noncerebral lesion.
9. Adequate organ function determined by the following requirements
10. Female patients of childbearing age have a negative serum pregnancy test result within 3 days before the first dose
11. If a female patient of childbearing potential has sex with an unsterilized male partner, the patient must use a highly effective method of contraception from the beginning of screening and must agree to continue using these precautions until 120 days after the last dose of the study drug or until 6 months after the last carboplatin and pemetrexed dose (whichever is longer).
12. If an unsterilized male patient has sex with a female partner of childbearing potential, the patient must use an effective method of contraception from the beginning of screening to day 120 after the last dose or until 6 months after the last carboplatin and pemetrexed dose (whichever is longer). The decision to stop contraception after this time point should be discussed with investigator.

Exclusion Criteria

1. Histologic or cytopathologic evidence of the presence of a small cell carcinoma component, or a predominantly squamous cell carcinoma.
2. Patients who have received immune checkpoint inhibitors (eg, anti-PD-1/L1 antibodies, anti-CTLA-4 antibodies, anti-LAG-3 antibodies, etc.)
3. Received prior systemic chemotherapy, anti-angiogenic therapy, or more than one prior line of antitumor therapy (other than EGFR inhibitors) for advanced stage (IIIB to IV) NSCLC.
4. Concurrent enrollment in another clinical study, unless it is a noninterventional clinical study or the follow-up period of the interventional study is more than 4 weeks from the last dose of the prior clinical study or more than 5 half-lives of the prior study drug, whichever is shorter.
5. Received EGFR inhibitor therapy within 2 weeks (with the exception of osimertinib to be within 7 days) prior to the first dose; received nonspecific immunomodulatory therapy (eg, interleukin, interferon, thymus peptide, tumor necrosis factor) within 2 weeks prior to the first dose, excluding IL-11 for the treatment of thrombocytopenia; have received Chinese herbal medicines or proprietary Chinese medicines with antitumor indications within 1 week before the first dose.
6. Imaging during the screening period shows that the tumor surrounds important blood vessels or has obvious necrosis and/or cavitation of tumor lesions within the lung parenchyma.
7. Imaging during the screening period shows that the tumor invades the surrounding vital organs and blood vessels, such as the heart and pericardium, trachea, esophagus, aorta, superior vena cava, or patient is at risk of esophageal tracheal fistula or esophageal pleural fistula.
8. Symptomatic metastases of the central nervous system.
9. Malignant tumors other than NSCLC within 3 years before the first dose.
10. Active autoimmune disease requiring systemic therapy (eg, with disease-modifying drugs, corticosteroids, immunosuppressant therapy) within 2 years prior to the first dose (excluding ir AEs due to PD-1/L1 inhibitors). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy (prednisone ≤ 10 mg daily or equivalent) for adrenal or pituitary insufficiency) is permitted.
11. There is a history of major diseases before the first dose
12. History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection, complicated by chronic diarrhea) within 6 months before the first study drug administration.
13. Patients with \>30 Gy of chest radiation therapy within 6 months prior to the first dose, nonthoracic radiation therapy \>30 Gy within 4 weeks prior to the first dose, and palliative radiation therapy of ≤30 Gy within 2 weeks prior to the first dose and failed to recover from the toxicity and/or complications of these interventions to NCI CTCAE Grade ≤1 (except hair loss and fatigue). Palliative radiotherapy for symptom control is permitted if it has been completed at least 2 weeks before the first dose, and no additional radiotherapy for the same lesion is planned.
14. Inactivated vaccines are allowed. Patients are excluded if they have received a live vaccine or live attenuated vaccine within 4 weeks prior to the first dose, or if they are scheduled to receive a live vaccine or live attenuated vaccine during the study period.
15. Severe infection within 4 weeks prior to the first dose, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection that has received systemic anti-infective therapy within 2 weeks prior to the first dose (excluding antiviral therapy for hepatitis B or C)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Akeso

INDUSTRY

Sponsor Role collaborator

Summit Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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CBCC Global Research

Bakersfield, California, United States

Site Status

UC San Diego

La Jolla, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

Valkyrie Clinical Trials

Los Angeles, California, United States

Site Status

UCLA Department of Medicine - Hematology/Oncology

Los Angeles, California, United States

Site Status

Palo Alto Medical Foundation Research Institute

Mountain View, California, United States

Site Status

Providence St. Joseph

Orange, California, United States

Site Status

UC Irvine

Orange, California, United States

Site Status

Sutter Cancer center

Sacramento, California, United States

Site Status

UC DAVIS Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Sharp Memorial Hospital

San Diego, California, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

Providence Medical Foundation

Santa Rosa, California, United States

Site Status

Presbyterian Intercommunity Hospital

Whittier, California, United States

Site Status

Rocky Mountain Cancer Center

Lone Tree, Colorado, United States

Site Status

The Oncology Institute of Hope & Innovation

Fort Lauderdale, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Florida Cancer Associates - Ocala Oncology

Ocala, Florida, United States

Site Status

BRCR Global

Plantation, Florida, United States

Site Status

Florida Cancer Specialists - North

St. Petersburg, Florida, United States

Site Status

BRCR Global

Tamarac, Florida, United States

Site Status

Florida Cancer Specialists -East

West Palm Beach, Florida, United States

Site Status

Hematology/Oncology Clinic - SCRI

Baton Rouge, Louisiana, United States

Site Status

New England Cancer Specialists

Scarborough, Maine, United States

Site Status

American Oncology Partners

Bethesda, Maryland, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

HealthPartners Cancer Research Center

Saint Paul, Minnesota, United States

Site Status

New York Oncology/Hematology

Clifton Park, New York, United States

Site Status

NYU Langone Laura and Isaac Perlmutter Cancer Center

New York, New York, United States

Site Status

Mount Sinai

New York, New York, United States

Site Status

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States

Site Status

Zangmeister Cancer Center

Columbus, Ohio, United States

Site Status

Oncology Hematology Care

Fairfield, Ohio, United States

Site Status

Williamette Valley Cancer Institute and Research

Eugene, Oregon, United States

Site Status

Kaiser Permanente Northwest

Portland, Oregon, United States

Site Status

Medical University South Carolina

Charleston, South Carolina, United States

Site Status

Baptist Hospital

Memphis, Tennessee, United States

Site Status

Texas Oncology South Austin

Austin, Texas, United States

Site Status

Texas Oncology Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status

MD Anderson University of Texas

Houston, Texas, United States

Site Status

Texas Oncology Webster

Webster, Texas, United States

Site Status

Virginia Cancer specialisits

Fairfax, Virginia, United States

Site Status

Compass Oncology

Vancouver, Washington, United States

Site Status

Cross cancer Institute

Edmonton, Alberta, Canada

Site Status

BC Cancer

Vancouver, British Columbia, Canada

Site Status

Lung Cancer Canada

Ottawa, Ontario, Canada

Site Status

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Allan Blaire Cancer Centre

Regina, Saskatchewan, Canada

Site Status

Universite Hospital Laval

Québec, , Canada

Site Status

CHI Creteil

Créteil, , France

Site Status

Léon Bérard Cancer Center, Lyon

Lyon, , France

Site Status

Hospital Bichat-Claude Bernard

Paris, , France

Site Status

Institut Curie

Paris, , France

Site Status

Gustave Roussy Cancer

Villejuif, , France

Site Status

Istituto Nazionale dei Tumori

Milan, , Italy

Site Status

Instituto Europeo di Oncologia

Milan, , Italy

Site Status

University Hospital of Parma

Parma, , Italy

Site Status

Campus Bio-Medico University

Roma, , Italy

Site Status

Istituto Nazionale Tumori, Regina Elena

Rome, , Italy

Site Status

Hospital Teresa Herrera

A Coruña, , Spain

Site Status

Vall d'Hebron Institute of Oncology

Barcelona, , Spain

Site Status

Badalona-Hospital Germans Trias i Pujol

Barcelona, , Spain

Site Status

omplejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria

Las Palmas, , Spain

Site Status

Lucus Augusti University Hospital

Lugo, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Universitario Clinico San Carlos

Madrid, , Spain

Site Status

Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Puerta de Hierro University Hospital

Majadahonda, , Spain

Site Status

Hospital Regional Universitario de Malaga

Málaga, , Spain

Site Status

Hospital Universitario Nuestro Senora de Valme

Seville, , Spain

Site Status

The Royal Marsden

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Countries

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United States Canada France Italy Spain United Kingdom

Other Identifiers

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AK112-301 (HARMONi)

Identifier Type: -

Identifier Source: org_study_id

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