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Recombinant Human Anti-PD-1 Monoclonal Antibody HX008 Injection for the Treatment of Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03704246
Recruitment Status : Recruiting
First Posted : October 12, 2018
Last Update Posted : October 12, 2018
Sponsor:
Information provided by (Responsible Party):
Taizhou Hanzhong biomedical co. LTD

Brief Summary:
In this study, patients of advanced gastric adenocarcinoma with failed first-line chemotherapy-line or advanced mismatched repair deficient (dMMR) or microsatellite instability-high (MSI-H) advanced solid carcinoma will be treated with HX008 combined with irinotecan and HX008 monotherapy There will be two cohorts in this study: Cohort 1 and Cohort 2. For Cohort 1, advanced gastric adenocarcinoma with failed first-line chemotherapy-line cancer participants, who had failed or were unable to tolerate first line chemotherapy with platinum-based or fluorouracil regimens. For Cohort 2, advanced solid tumor participants, who are required to have been previously treated with at least one line of systemic standard of care therapy.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: Anti-PD-1 monoclonal antibody Phase 2

Detailed Description:

Cohort 1:

Currently, no PD-1 antibody against gastric cancer have been approved in China, and there are many patients with gastric cancer in China, so effective, low-toxicity and affordable treatment is urgently needed. This study aims to investigate the efficacy of combined application of recombinant human anti-PD-1 monoclonal antibody (HX008) and irinotecan in patients with locally advanced or metastatic gastric cancer (including gastric esophageal junction cancer) ,thus providing a better treatment for Chinese patients with gastric cancer.Advanced gastric adenocarcinoma with failed first-line chemotherapy-line cancer participants, who had failed or were unable to tolerate first line chemotherapy with platinum-based or fluorouracil regimens are needed.

Cohort 2:

Later-line therapies after failure of standard treatments for advanced solid cancer patients are limited. Mismatch repair (MMR) deficiency or microsatellite instability-high (MSI-H) played a role of positive predictive factor, which had been documented after the pembrolizumab and nivolumab trial were reported, for PD-1 blockade monotherapy in patients with advanced solid carcinomas.

In this study, patients with previously-treated locally-advanced or metastatic mismatched repair deficient (dMMR) or microsatellite instability-high (MSI-H) advanced solid tumors will be treated with HX008 monotherapy.Advanced solid tumor participants, who are required to have been previously treated with at least one line of systemic standard of care therapy are needed.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 123 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open and Phase II Clinical Study of HX008 for the Treatment in Patients With Advanced Solid Tumors
Actual Study Start Date : September 30, 2018
Estimated Primary Completion Date : December 30, 2019
Estimated Study Completion Date : March 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Anti-PD-1
Anti-PD-1 monoclonal antibody HX008 injection with a dose of 200mg (intravenous infusion, every 3 weeks)
Drug: Anti-PD-1 monoclonal antibody
HX008 is a monoclonal antibody drug which is intravenous drip at a dose of 200mg.
Other Name: HX008




Primary Outcome Measures :
  1. ORR of HX008 combined with irinotecan and HX008 single drug [ Time Frame: Up to approximately 2 years ]
    ORR was assessed according to Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST 1.1)


Secondary Outcome Measures :
  1. HX008 safety and tolerability assessed by monitoring AEs [ Time Frame: From screening to up to 1 months after the last dose of study drug (up to approximately 2 years) ]
    Percentage of participants with adverse events (AEs), serious adverse events and AEs of special interest

  2. Disease Control Rate (DCR) [ Time Frame: Up to approximately 2 years ]
    per RECIST 1.1 assessed by central imaging vendor and investigator

  3. Duration of Response (DOR) [ Time Frame: Up to approximately 2 years ]
    per RECIST 1.1 assessed by central imaging vendor and investigator

  4. Progression-Free Survival (PFS) [ Time Frame: Up to approximately 2 years ]
    per RECIST 1.1 assessed by central imaging vedor and investigator

  5. Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    Calculated by the Kaplan-Meier method.

  6. Immunogenicity [ Time Frame: From the first dose of study drug (up to approximately 2 years) ]
    Measured by MSD electroluminescence detection method



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main inclusion Criteria:

  1. Subject is male or female ≥ 18 years and ≤ 70 years of age on the day of signing informed consent,and subject has voluntarily agreed to participate by giving written informed consent.
  2. Subjects must have a histopathological diagnosis of any locally advanced or metastatic solid tumor, Subjects must have failed established standard medical anti-cancer therapies ( have disease progression after the therapies or be intolerant to the therapies) or Subjects refuse to standard therapies, or no effective treatment.
  3. Subject must have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  4. Measurable disease as defined by RECIST v1.1.
  5. Life expectancy ≥ 12 weeks.
  6. Subject must have adequate hematologic and organ function.
  7. Asymptomatic patients with Central Nervous System (CNS) metastasis or asymptomatic brain metastasis after treatment shall undergo computed tomography (CT) or magnetic resonance imaging (MRI) for no disease progression, stable for at least 3 months and no steroid treatment for at least 4 weeks.
  8. Male subjects and female subjects should agree to take effective contraception from the date of signing the informed consent form until 3 months after the last administration.

Special inclusion criteria 1 in the Cohort 1.

  1. Locally advanced or metastatic gastric adenocarcinoma (including gastric esophageal junction cancer) diagnosed histologically or cytologically.
  2. Participants who had previously received a platinum-based or fluorouracil based first-line chemotherapy failed or could not tolerate.
  3. The final cytotoxic drug, radiotherapy, or surgery≥4 weeks away. Special inclusion criteria 1 in the Cohort 2

1.Advanced malignant solid tumors confirmed by histology or cytology and confirmed as msi-h or dMMR by the central laboratory designated by the sponsor.

2.Participants must have received or not tolerated a first-line anti-tumor drug regimen.

Main exclusion Criteria:

  1. Participants with other malignant tumors within 5 years before enrollment, excluding cured cervical carcinoma in situ and cured basal cell carcinoma of the skin.
  2. Subject Is currently participating and receiving study therapy or has participated in a study of an investigational agent and receive study therapy within 28 days of the first dose of study drug.
  3. Subject has not recovered to CTCAE Grade 1 or better from the adverse events due to cancer therapeutics administered.
  4. Subject who had received anti-PD-1, PD-L1-,CTLA-4 monoclonal therapy, etc.
  5. Subjects with active, or pre-existing, autoimmune diseases that may recur.
  6. Systemic corticosteroids should be administered within 14 days before initial administration or during the study.
  7. Subjects with active gastrointestinal ulcer, incomplete intestinal obstruction, active gastrointestinal hemorrhage and perforation.
  8. Subjects with existing interstitial lung or pneumonia, pulmonary fibrosis, acute pulmonary disease, radioactive pneumonia;
  9. Subjects with Uncontrollable and stable systemic diseases, such as cardiovascular and cerebrovascular diseases, diabetes, hypertension and tuberculosis.
  10. Subjects with a history of infection with human immunodeficiency virus, or have other acquired or congenital immune deficiency diseases, or have a history of organ transplantation or stem cell transplantation.
  11. Subject is positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active hepatitis B (HBV surface antigen positive and HBV DNA ≥ 500 copies/ml)or hepatitis C or tuberculosis (HCV antibody positive).
  12. Subjects with severe infection within 4 weeks before first administration, or those with active infection within 2 weeks before administration or intravenous antibiotic treatment.
  13. Subjects who have been previously known to have severe allergic reactions to macromolecules/monoclonal antibodies or to any of the test drug components (CTCAE ≥Grade 3).
  14. Participated in clinical trials of other drugs within 4 weeks before the first administration (subject to the use of the tested drugs).
  15. Subjects with alcohol dependence or a history of drug abuse or drug abuse within one year.
  16. Subjects with a clear history of neurological or mental disorders, such as epilepsy, dementia, poor compliance, or peripheral nervous system disorders;
  17. Subjects with symptomatic brain metastases.
  18. Women who are pregnant or lactating.
  19. Subjects were not fit for other reasons concluded by the researchers.

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): NCT03704246


Contacts
Contact: Zhengang Xu, MD 86-10-87788495 cancergcp@163.com
Contact: Jing Huang, MD 86-13301056087 huangjingwg@163.com

Locations
China, Beijing
Cancer Hospital, Chinese Academy of Medical Sciences Recruiting
Beijing, Beijing, China, 100021
Contact: Jing Huang, MD    86-13301056087    huangjingwg@163.com   
Contact: Jing Yang, MD    86-15971460298    jing.yang@hanxbio.com   
Sponsors and Collaborators
Taizhou Hanzhong biomedical co. LTD

Responsible Party: Taizhou Hanzhong biomedical co. LTD
ClinicalTrials.gov Identifier: NCT03704246     History of Changes
Other Study ID Numbers: hanxbio
First Posted: October 12, 2018    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs