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Recombinant Humanized Anti-CD47 / PD-1 Bifunctional Antibody HX009 Injection in the Treatment of Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04886271
Recruitment Status : Recruiting
First Posted : May 14, 2021
Last Update Posted : May 18, 2021
Sponsor:
Information provided by (Responsible Party):
Waterstone Hanxbio Pty Ltd

Brief Summary:
This is a multi-center phase II clinical trial to evaluate the anti-tumor activity and safety of HX009 in subjects with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: HX009 Phase 2

Detailed Description:

The present study is comprised of two parts: the efficacy estimation part and the key phase II part. In the first part, subjects with unresectable locally advanced or metastatic solid tumors (confirmed by histology or pathology) will be enrolled. Tumor types of special interest include biliary cancers, head and neck cancers, esophageal cancers, sarcoma, and malignant mesothelioma, and at least 8 subjects will be enrolled for each of these tumor types. Subjects with biliary cancers and other tumor types based on the efficacy data of the first part will be enrolled in the second part of the study.

Subjects will receive HX009 via intravenous infusion at 5 mg/Kg once every 2 weeks. Treatment will continue until loss of clinical benefit at the discretion of the investigator, or intolerable toxicity, or withdrawal of consent, or disease progression, or death, or loss of follow-up (whichever occurs first). The maximum duration of treatment with HX009 is one year.

Tumor evaluation is conducted by the investigator according to the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and immune RECIST (iRECIST), and is repeated every 6 weeks. Adverse events (AEs) are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Phase II Clinical Study of Recombinant Humanized Anti-CD47 / PD-1 Bifunctional Antibody HX009 Injection in the Treatment of Advanced Solid Tumors
Estimated Study Start Date : May 10, 2021
Estimated Primary Completion Date : December 10, 2022
Estimated Study Completion Date : February 10, 2023

Arm Intervention/treatment
Experimental: HX009 Drug: HX009
Eligible participants will receive HX009 treatment at 5mg/Kg via IV infusion over 60-120 minutes, and the scheduled dosing cycle is once every 2 weeks.




Primary Outcome Measures :
  1. Objective response rate (ORR) of patients with solid tumors treated with HX009 assessed by the Independent Review Committee (IRC) [ Time Frame: Approximately 1 year ]
    The ORR is defined as the percentage of participants in the analysis population who had a confirmed Complete Response or Partial Response using RECIST 1.1 criteria.


Secondary Outcome Measures :
  1. Objective response rate(ORR) of patients with solid tumors treated with HX009 per Investigator Assessment [ Time Frame: Approximately 1 year ]
    The ORR is defined as the percentage of participants in the analysis population who had a confirmed Complete Response or Partial Response using RECIST 1.1 criteria.

  2. Duration of response (DoR) of patients with solid tumors treated with HX009 [ Time Frame: Approximately 1 year ]
    The DoR is defined as the time from the first recorded response (CR or PR) to the first recorded tumor progression or death due to any cause.

  3. Disease control rate (DCR) of patients with solid tumors treated with HX009 [ Time Frame: Approximately 1 year ]
    The DCR is defined as the percentage of participants in the analysis population who had a confirmed Complete Response, or Partial Response, or Stable Disease using RECIST 1.1 criteria.

  4. Progression-free survival (PFS) of patients with solid tumors treated with HX009 [ Time Frame: Approximately 1 year ]
    PFS is defined as the time from the start of the first dose and the first documented disease progression using RECIST 1.1 criteria or death of any cause.

  5. Overall survival (OS) of patients with solid tumors treated with HX009 [ Time Frame: Approximately 1 year ]
    OS is defined as the time between the start of the first dose and death of any cause.

  6. Incidence of treatment-related adverse events in patients with advanced solid tumors treated with HX009 [ Time Frame: AEs will be collected from the start of the study treatment up to 90 days after the last dose. ]
    Adverse events (AEs) related to HX009 as determined by the investigator are recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0).

  7. Severity of treatment-related adverse events in patients with advanced solid tumors treated with HX009 [ Time Frame: AEs will be collected from the start of the study treatment up to 90 days after the last dose. ]
    Adverse events (AEs) related to HX009 as determined by the investigator are recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0).

  8. Number of patients having detectable anti-drug antibody (ADA) of HX009 [ Time Frame: Approximately 1 year ]
    Detection of ADA is a measure of immunogenicity of HX009

  9. Number of patients having detectable neutralizing antibody (Nab) of HX009 [ Time Frame: Approximately 1 year ]
    Detection of Nab is a measure of immunogenicity of HX009

  10. Elimination half-life (t1/2β) of HX009 in patients with advanced solid tumors [ Time Frame: Approximately 1 year ]
    Key pharmacokinetic parameter

  11. Mean residence time in the body (MRT) of HX009 in patients with advanced solid tumors [ Time Frame: Approximately 1 year ]
    Key pharmacokinetic parameter

  12. Area under the concentration-time curve (AUC0-t) of HX009 in patients with advanced solid tumors [ Time Frame: Approximately 1 year ]
    Key pharmacokinetic parameter

  13. Peak plasma concentration (Cmax) of HX009 in patients with advanced solid tumors [ Time Frame: Approximately 1 year ]
    Key pharmacokinetic parameter

  14. Time to peak plasma concentration (Tmax) of HX009 in patients with advanced solid tumors [ Time Frame: Approximately 1 year ]
    Key pharmacokinetic parameter



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, aged 18 to 75 years, inclusive;
  2. Eastern Cooperative Oncology Group performance status of 0 to 1;
  3. Having unresectable locally advanced or metastatic solid tumor (confirmed by histology or pathology);
  4. Participants must have failed the standard treatment (due to either disease progression or intolerable toxicity) or the standard of care had not been established for the specific condition;
  5. Measurable extracranial lesion based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1;
  6. Life expectancy ≥12 weeks;
  7. For prior anti-tumor therapies, the following conditions must be met:

    • The interval between local radiotherapy or radiotherapy for bone metastasis and the first dose of is ≥2 weeks;
    • The interval between the last dose of previous chemotherapy, immunotherapy (including PD-1, PD-L1 or CTLA-4 antibodies), biological therapy (tumor vaccines, cytokines, or anti-cancer growth factors) and the first dose of HX009 is ≥4 weeks (The interval between the last dose of small molecule targeted drugs and the first dose of HX009 is ≥2 weeks);
    • The interval between the last dose of anti-cancer Traditional Chinese Medicine and the first dose of HX009 is ≥ 2 weeks;
    • Has had previously serious adverse reactions (pneumonia or myocarditis) related to previous PD1/PDL1 inhibitors that preclude their treatment according to the investigator's criteria;
  8. Participants with asymptomatic central nervous system (CNS) metastases are eligible only if they have no evidence of progression by imaging for at least four weeks prior to the first dose of HX009 and are not using corticosteroids;
  9. Appropriate organ functions according to the following laboratory tests :

    • Absolute neutrophil count (ANC)≥1.5 × 10^9/L
    • Absolute white blood cell count (WBC) ≥3.0×10^9/L
    • Platelet count ≥90 × 10^9/L
    • Hemoglobin ≥90 g/L (no blood transfusion within 4 weeks prior to HX009 administration)
    • Serum creatinine≤1.5 upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN , ALT and AST ≤5 × ULN for subjects with liver metastases or liver cancer
    • Serum Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN)
    • International normalized ratio (INR) ≤ 2 x ULN, or activated partial thromboplastin time (APTT) ≤ 1.5 x ULN (except for patients receiving anticoagulant therapy) ;
  10. Reproductive males or females who are likely to become pregnant must use highly effective contraceptive methods (such as oral contraceptives, intrauterine contraceptives, sexual control or barrier contraceptives combined with spermicides) during the trial, and continue contraception for 6 months after the last dose of HX009;
  11. Participants must be willing and able to provide written informed consent for the study, and have good compliance;

Exclusion Criteria:

  1. Participants having a known additional malignancy within 3 years before enrollment, except for malignancies with low risk of metastasis and death (5-year survival rate> 90%), such as completely resected basal cell or squamous cell skin cancer, or cervical carcinoma in situ, or superficial bladder cancer;
  2. Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. (Subjects with > Grade 1 neuropathy or hair loss are an exception to this criterion and may qualify for the study according to the judgment of the investigator);
  3. Participants with active or history of autoimmune diseases are ineligible, except for the following conditions:

    • Participants with type 1 diabetes who are in stable condition after using a fixed dose of insulin;
    • Autoimmune hypothyroidism requiring only hormone replacement therapy;
    • Autoimmune skin diseases that do not require systemic treatment (such as eczema, skin rashes that account for less than 10% of the body surface, or psoriasis without ophthalmological symptoms);
  4. Participants expected to undergo major surgery within 28 days before the planned first dose of HX009;
  5. Participants receiving systemic corticosteroids equivalent to >10 mg prednisone/day or other immunosuppressive drugs within 14 days before the first administration of HX009, except for the following conditions:

    • Participants using topical or inhaled corticosteroids;
    • Short-term (≤7 days) use of corticosteroids to prevent or treat non-autoimmune allergic diseases;
  6. Participants with known interstitial lung disease or non-infectious pneumonia requiring systemic treatment with corticosteroids;
  7. Participants having clinically serious cardiovascular diseases (unstable angina or myocardial infarction within 6 months before enrollment), diabetes, or hypertension;
  8. Participants having arterial or venous thrombosis or embolic events (cerebrovascular events including transient ischemic attack, deep vein thrombosis, or pulmonary embolism) within 6 months before the first administration of HX009;
  9. Participants having a history of human immunodeficiency virus infection, or having other acquired or congenital immunodeficiency diseases, or having a history of organ or stem cell transplantation;
  10. Participants with active chronic hepatitis B or active hepatitis C;
  11. Participants having a serious infection within 4 weeks before the first administration of HX009, or having an active infection that require oral or intravenous antibiotic treatment;
  12. Participants having severe allergic reactions to macromolecular protein preparations/monoclonal antibodies, or to any drug component of HX009 (CTCAE 5.0 grade greater than 3);
  13. Participated in other drug clinical trials within 4 weeks before the first administration of HX009;
  14. Alcohol dependent or known history of drug abuse within the past year;
  15. Participants with poor compliance due to known history of neurological or mental disorders, such as epilepsy, dementia;
  16. Pregnant or breastfeeding women;
  17. Participants with pleural effusion, abdominal effusion or pericardial effusion with clinical symptoms;
  18. Participants having received colony-stimulating factor, granulocyte macrophage colony-stimulating factor or recombinant erythropoietin within 2 weeks prior to the start of treatment;
  19. Participants, in the judgement of the investigator, who are unlikely to comply with the study procedures, restrictions, and requirements of the study.

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): NCT04886271


Contacts
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Contact: Qian Jiang +8618600110741 qian.jiang@hanxbio.com

Locations
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China, Guangdong
Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center Recruiting
Shenzhen, Guangdong, China
Contact: Jing Huang, MD         
Sponsors and Collaborators
Waterstone Hanxbio Pty Ltd
Investigators
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Principal Investigator: Jing Huang, MD Chinese Academy of Medical Sciences
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Responsible Party: Waterstone Hanxbio Pty Ltd
ClinicalTrials.gov Identifier: NCT04886271    
Other Study ID Numbers: HX009-II-01
First Posted: May 14, 2021    Key Record Dates
Last Update Posted: May 18, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms