Phase III Study of AK112 for NSCLC Patients

NCT06396065 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AK112-301 (HARMONi)
• Study Type: interventional
• Target: 420
• Locations: 6 countries
• Sites: 74

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)

Conditions

Non-Squamous Non-small Cell Lung Cancer

Keywords

NSCLC; EGFR Positive; ivonescimab

Outcome Measures

Primary Outcomes (2)

• Progression-free survival (PFS)

  Progression-free survival (PFS) assessed by IRC per RECIST v1.1 in the ITT population.

  Up to 2 years

• Overall Survival (OS) in the ITT population

  Overall Survival (OS) in the ITT population

  Up to 2 years

Secondary Outcomes (5)

• ORR

  Up to 2 years

• 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

• Observed concentrations of AK112

  through study completion, an average of 2 years

• 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

• DoR

  Up to 2 years

Study Arms (2)

AK112 in combination with Pemetrexed and Carboplatin

EXPERIMENTAL

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.

Drug: AK112 Injection

Placebo in combination with Pemetrexed and Carboplatin

ACTIVE COMPARATOR

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.

Drug: Placebo Injection

Interventions

AK112 Injection 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.

Also known as: Pemetrexed, Carboplatin

AK112 in combination with Pemetrexed and Carboplatin

Placebo Injection 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.

Also known as: Pemetrexed, Carboplatin

Placebo in combination with Pemetrexed and Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Summit Therapeutics: lead
• Akeso: collaborator

Study Sites (74)

CBCC Global Research

Bakersfield, California, 93309, United States

Location

UC San Diego

La Jolla, California, 92093, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

Location

UCLA Department of Medicine - Hematology/Oncology

Los Angeles, California, 90095, United States

Location

Palo Alto Medical Foundation Research Institute

Mountain View, California, 94040, United States

Location

Providence St. Joseph

Orange, California, 92868, United States

Location

UC Irvine

Orange, California, 92868, United States

Location

Sutter Cancer center

Sacramento, California, 95816, United States

Location

UC DAVIS Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

Providence Medical Foundation

Santa Rosa, California, 95403, United States

Location

Presbyterian Intercommunity Hospital

Whittier, California, 90602, United States

Location

Rocky Mountain Cancer Center

Lone Tree, Colorado, 80124, United States

Location

The Oncology Institute of Hope & Innovation

Fort Lauderdale, Florida, 33308, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Florida Cancer Associates - Ocala Oncology

Ocala, Florida, 34474, United States

Location

BRCR Global

Plantation, Florida, 33322, United States

Location

Florida Cancer Specialists - North

St. Petersburg, Florida, 33705, United States

Location

BRCR Global

Tamarac, Florida, 33321, United States

Location

Florida Cancer Specialists -East

West Palm Beach, Florida, 33401, United States

Location

Hematology/Oncology Clinic - SCRI

Baton Rouge, Louisiana, 70809, United States

Location

New England Cancer Specialists

Scarborough, Maine, 04074, United States

Location

American Oncology Partners

Bethesda, Maryland, 20817, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

HealthPartners Cancer Research Center

Saint Paul, Minnesota, 55101, United States

Location

New York Oncology/Hematology

Clifton Park, New York, 12065, United States

Location

NYU Langone Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58102, United States

Location

Zangmeister Cancer Center

Columbus, Ohio, 43219, United States

Location

Oncology Hematology Care

Fairfield, Ohio, 45014, United States

Location

Williamette Valley Cancer Institute and Research

Eugene, Oregon, 97401, United States

Location

Kaiser Permanente Northwest

Portland, Oregon, 97227, United States

Location

Medical University South Carolina

Charleston, South Carolina, 29425, United States

Location

Baptist Hospital

Memphis, Tennessee, 38120, United States

Location

Texas Oncology South Austin

Austin, Texas, 78745, United States

Location

Texas Oncology Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

MD Anderson University of Texas

Houston, Texas, 77030, United States

Location

Texas Oncology Webster

Webster, Texas, 77598, United States

Location

Virginia Cancer specialisits

Fairfax, Virginia, 22031, United States

Location

Compass Oncology

Vancouver, Washington, 98684, United States

Location

Cross cancer Institute

Edmonton, Alberta, T6g 1Z2, Canada

Location

BC Cancer

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Lung Cancer Canada

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5g 2M9, Canada

Location

Allan Blaire Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Universite Hospital Laval

Québec, G1V 4G5, Canada

Location

CHI Creteil

Créteil, 94010, France

Location

Léon Bérard Cancer Center, Lyon

Lyon, 69008, France

Location

Hospital Bichat-Claude Bernard

Paris, 75018, France

Location

Institut Curie

Paris, 75248, France

Location

Gustave Roussy Cancer

Villejuif, 94800, France

Location

Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Instituto Europeo di Oncologia

Milan, 20141, Italy

Location

University Hospital of Parma

Parma, 43126, Italy

Location

Campus Bio-Medico University

Roma, 00128, Italy

Location

Istituto Nazionale Tumori, Regina Elena

Rome, 00144, Italy

Location

Hospital Teresa Herrera

A Coruña, 15006, Spain

Location

Vall d'Hebron Institute of Oncology

Barcelona, 08035, Spain

Location

Badalona-Hospital Germans Trias i Pujol

Barcelona, 08916, Spain

Location

omplejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria

Las Palmas, 35016, Spain

Location

Lucus Augusti University Hospital

Lugo, 27002, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Clinico San Carlos

Madrid, 28040, Spain

Location

Instituto de Investigacion Sanitaria-Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Puerta de Hierro University Hospital

Majadahonda, 28222, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29011, Spain

Location

Hospital Universitario Nuestro Senora de Valme

Seville, 41014, Spain

Location

The Royal Marsden

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4GJ, United Kingdom

Location

MeSH Terms

Interventions

Pemetrexed; Carboplatin

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: May 2, 2024
• Study Start: May 4, 2023
• Primary Completion: April 12, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

CA (6); ES (13); IT (5); FR (5); GB (2); US (43)