Phase III Study of AK112 for NSCLC Patients
- Conditions
- Non-Squamous Non-small Cell Lung Cancer
- Interventions
- Drug: AK112 InjectionDrug: Placebo Injection
- Registration Number
- NCT06396065
- Lead Sponsor
- Summit Therapeutics
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 420
- 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.
- 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)
- ECOG performance status score of 0 or 1.
- Expected survival ≥3 months.
- 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.
- 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.
- 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.
- According to RECIST v1.1, there is at least 1 measurable noncerebral lesion.
- Adequate organ function determined by the following requirements
- Female patients of childbearing age have a negative serum pregnancy test result within 3 days before the first dose
- 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).
- 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.
- Histologic or cytopathologic evidence of the presence of a small cell carcinoma component, or a predominantly squamous cell carcinoma.
- Patients who have received immune checkpoint inhibitors (eg, anti-PD-1/L1 antibodies, anti-CTLA-4 antibodies, anti-LAG-3 antibodies, etc.)
- 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.
- 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.
- 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.
- 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.
- 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.
- Symptomatic metastases of the central nervous system.
- Malignant tumors other than NSCLC within 3 years before the first dose.
- 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.
- There is a history of major diseases before the first dose
- 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.
- 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.
- 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.
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AK112 in combination with Pemetrexed and Carboplatin 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. Placebo in combination with Pemetrexed and Carboplatin 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) in the ITT population Up to 2 years Overall Survival (OS) in the ITT population
Progression-free survival (PFS) Up to 2 years Progression-free survival (PFS) assessed by IRC per RECIST v1.1 in the ITT population.
- Secondary Outcome Measures
Name Time Method ORR Up to 2 years Efficacy measures such as overall response rate (ORR) and duration of response (DoR), which is the proportion of subjects with CR or PR by IRRC based on RECIST v1.1
AE From the subject signs the ICF to 30 days (AE) and 90 days (SAE) after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first,up to 2 years Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results.
Observed concentrations of AK112 through study completion, an average of 2 years The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration
DoR Up to 2 years Duration of response (DoR) which is the proportion of subjects with CR or PR by IRRC based on RECIST v1.1
Number of subjects who develop detectable anti-drug antibodies (ADAs) From first dose of AK112 through 90 days after last dose of AK112, up to 2 years The immunogenicity of AK112 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs)
Trial Locations
- Locations (73)
CBCC Global Research
🇺🇸Bakersfield, California, United States
UC San Diego
🇺🇸La Jolla, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Valkyrie Clinical Trials
🇺🇸Los Angeles, California, United States
UCLA Department of Medicine - Hematology/Oncology
🇺🇸Los Angeles, California, United States
Palo Alto Medical Foundation Research Institute
🇺🇸Mountain View, California, United States
Providence St. Joseph
🇺🇸Orange, California, United States
UC Irvine
🇺🇸Orange, California, United States
Sutter Cancer center
🇺🇸Sacramento, California, United States
UC DAVIS Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Providence Medical Foundation
🇺🇸Santa Rosa, California, United States
Presbyterian Intercommunity Hospital
🇺🇸Whittier, California, United States
Rocky Mountain Cancer Center
🇺🇸Lone Tree, Colorado, United States
The Oncology Institute of Hope & Innovation
🇺🇸Fort Lauderdale, Florida, United States
Florida Cancer Specialists - North
🇺🇸Saint Petersburg, Florida, United States
University of Miami
🇺🇸Miami, Florida, United States
Florida Cancer Specialists -East
🇺🇸West Palm Beach, Florida, United States
Hematology/Oncology Clinic - SCRI
🇺🇸Baton Rouge, Louisiana, United States
New England Cancer Specialists
🇺🇸Scarborough, Maine, United States
Florida Cancer Associates - Ocala Oncology
🇺🇸Ocala, Florida, United States
BRCR Global
🇺🇸Tamarac, Florida, United States
American Oncology Partners
🇺🇸Bethesda, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
HealthPartners Cancer Research Center
🇺🇸Saint Paul, Minnesota, United States
New York Oncology/Hematology
🇺🇸Clifton Park, New York, United States
NYU Langone Laura and Isaac Perlmutter Cancer Center
🇺🇸New York, New York, United States
Mount Sinai
🇺🇸New York, New York, United States
Sanford Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
Zangmeister Cancer Center
🇺🇸Columbus, Ohio, United States
Oncology Hematology Care
🇺🇸Fairfield, Ohio, United States
Williamette Valley Cancer Institute and Research
🇺🇸Eugene, Oregon, United States
Kaiser Permanente Northwest
🇺🇸Portland, Oregon, United States
Medical University South Carolina
🇺🇸Charleston, South Carolina, United States
Baptist Hospital
🇺🇸Memphis, Tennessee, United States
Texas Oncology South Austin
🇺🇸Austin, Texas, United States
Texas Oncology Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
MD Anderson University of Texas
🇺🇸Houston, Texas, United States
Texas Oncology Webster
🇺🇸Webster, Texas, United States
Virginia Cancer specialisits
🇺🇸Fairfax, Virginia, United States
Compass Oncology
🇺🇸Vancouver, Washington, United States
Cross cancer Institute
🇨🇦Edmonton, Alberta, Canada
BC Cancer
🇨🇦Vancouver, British Columbia, Canada
Lung Cancer Canada
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Allan Blaire Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Universite Hospital Laval
🇨🇦Québec, Canada
CHI Creteil
🇫🇷Creteil, France
Léon Bérard Cancer Center, Lyon
🇫🇷Lyon, France
Hospital Bichat-Claude Bernard
🇫🇷Paris, France
Institut Curie
🇫🇷Paris, France
Gustave Roussy Cancer
🇫🇷Villejuif, France
Istituto Nazionale dei Tumori
🇮🇹Milan, Italy
Instituto Europeo di Oncologia
🇮🇹Milan, Italy
University Hospital of Parma
🇮🇹Parma, Italy
Campus Bio-Medico University
🇮🇹Roma, Italy
Istituto Nazionale Tumori, Regina Elena
🇮🇹Rome, Italy
Vall d'Hebron Institute of Oncology
🇪🇸Barcelona, Spain
Badalona-Hospital Germans Trias i Pujol
🇪🇸Barcelona, Spain
Hospital Teresa Herrera
🇪🇸Coruña, Spain
omplejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria
🇪🇸Las Palmas, Spain
Lucus Augusti University Hospital
🇪🇸Lugo, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Clinico San Carlos
🇪🇸Madrid, Spain
Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Puerta de Hierro University Hospital
🇪🇸Majadahonda, Spain
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Hospital Universitario Nuestro Senora de Valme
🇪🇸Sevilla, Spain
The Royal Marsden
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom