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Phase 3 Clinical Study of AK112 for NSCLC Patients

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ClinicalTrials.gov Identifier: NCT05184712
Recruitment Status : Recruiting
First Posted : January 11, 2022
Last Update Posted : May 25, 2023
Sponsor:
Collaborator:
Akeso
Information provided by (Responsible Party):
Summit Therapeutics

Study Description
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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)

Condition or disease Intervention/treatment Phase
Non-Squamous Non-small Cell Lung Cancer Drug: AK112 Injection Drug: Placebo Injection Phase 3

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 470 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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 470 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Multi-center, Phase III Study of AK112 or Placebo Combined With Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous NSCLC Who Have Failed to EGFR-TKI Treatment
Actual Study Start Date : January 1, 2022
Estimated Primary Completion Date : January 1, 2025
Estimated Study Completion Date : January 1, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: 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.
Other Names:
  • Pemetrexed
  • Carboplatin
Placebo Comparator: 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.
 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.
Other Names:
  • Pemetrexed
  • Carboplatin


Outcome Measures
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Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    Progression-free survival (PFS) assessed by IRC per RECIST v1.1 in the ITT population.

  2. Overall Survival (OS) [ Time Frame: Up to 2 years ]
    Overall Survival (OS) in the ITT population


Secondary Outcome Measures :
  1. ORR [ Time Frame: Up to 2 years ]
    Efficacy measures such as overall response rate (ORR), which is the proportion of subjects with CR or PR by IRRC based on RECIST v1.1

  2. DCR [ Time Frame: Up to 2 years ]
    Disease control rate (DCR), which is defined as the proportion of subjects with CR, PR, or SD, based on RECIST v1.1

  3. DoR [ Time Frame: Up to 2 years ]
    Duration of response (DoR), which is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.

  4. TTR [ Time Frame: Up to 2 years ]
    TTR is defined as the time to response base on RECIST v1.1

  5. PFS [ Time Frame: Up to 2 years ]
    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first assessed by investigator Per RECIST 1.1.

  6. AE [ Time Frame: 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.

  7. Observed concentrations of AK112 [ Time Frame: through study completion, an average of 2 year ]
    The endpoints for assessment of PK of AK112 include serum concentrations of AK112 at different timepoints after AK112 administration

  8. Number of subjects who develop detectable anti-drug antibodies (ADAs) [ Time Frame: 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)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 years at the time of signing informed consent.
  3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
  4. Life expectancy ≥3 months；
  5. Locally advanced (stage IIIB/IIIC) or metastatic (stage IV) non-squamous NSCLC confirmed by histology or cytology, inoperable and unable to receive radiotherapy and chemotherapy;
  6. The tumor histology, cytology or hematology confirmed the presence of EGFR activating mutations before enrollment
  7. Have previously received 3rd generation EGFR-TKI treatment and have progressed on or following
  8. Subjects have at least one measurable non-brain tumor lesion per RECIST v1.1
  9. Major organ function prior to treatment meets the following criteria
  10. Patients of childbearing potential must agree to use effective contraceptive measures

Exclusion Criteria:

  1. Histological or cytological pathology confirmed the presence of small cell carcinoma components, or the main component is squamous cell carcinoma
  2. There are reports confirming the existence of other driver gene mutations with known drug treatments
  3. Subjects who received any prior treatments targeting the mechanism of tumor immunity
  4. The subject has received systemic anti-tumor therapy other than EGFR-TKI
  5. Currently enrolled in any other clinical study
  6. Received EGFR-TKI treatment, palliative local treatment, non-specific immunomodulatory treatment within 2 weeks prior to the first dose.
  7. Tumor surrounds important blood vessels or has obvious necrosis, cavitation, or invades surrounding important organs and blood vessels.
  8. Symptomatic central nervous system metastases
  9. Active malignancies within the past 3 years, with the exception of tumors in this study and cured local tumors
  10. Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment
  11. There is a history of major diseases 1 year prior to the first dose.
  12. .Medical history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose
  13. Received chest radiation therapy prior to the first dose
  14. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage.
  15. Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05184712


Contacts
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Contact: Lori Styles, MD 1-833-256-0522 medicalinformation@smmttx.com

Locations
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United States, California
Research Site Not yet recruiting
Los Angeles, California, United States, 90024
Research Site Not yet recruiting
Orange, California, United States, 92868
Research Site Recruiting
Santa Rosa, California, United States, 95404
United States, Florida
Research Site Not yet recruiting
Ocala, Florida, United States, 34471
Research Site Recruiting
Plantation, Florida, United States, 33322
United States, Illinois
Research Site Not yet recruiting
Chicago, Illinois, United States, 92037
Canada, Alberta
Research Site Not yet recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Research Site Not yet recruiting
Vancouver, British Columbia, Canada, V5Z 1L3
Canada, Ontario
Research Site Not yet recruiting
Ottawa, Ontario, Canada, K1H 8L6
Research Site Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Canada
Research Site Not yet recruiting
Québec, Canada, V5Z 1H6
China, Guangdong
Sun Yat-sen University Cancer Center Recruiting
Guangzhou, Guangdong, China, 510000
Contact: Li Zhang, Master    139 0228 2893      
France
Research Site Not yet recruiting
Paris, France, 75018
Italy
Research Site Not yet recruiting
Roma, Italy, 00128
Spain
Research Site Not yet recruiting
Madrid, Spain, 28034
United Kingdom
Research Site Not yet recruiting
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Summit Therapeutics
Akeso
Investigators
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Principal Investigator: Li Zhang, MD Sun Yat-sen University
More Information
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Responsible Party: Summit Therapeutics
ClinicalTrials.gov Identifier: NCT05184712    
Other Study ID Numbers: AK112-301
HARMONi ( Other Identifier: Summit Therapeutics )
First Posted: January 11, 2022    Key Record Dates
Last Update Posted: May 25, 2023
Last Verified: May 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
 Respiratory Tract Diseases
Carboplatin
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors