ClinicalTrials.gov
ClinicalTrials.gov Menu

A Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Anti-PD-1 Antibody (HLX10) in Combination With Avastin Biosimilar (HLX04) in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03757936
Recruitment Status : Not yet recruiting
First Posted : November 29, 2018
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
Shanghai Henlius Biotech

Brief Summary:
This is a single-center, open-label, dose-escalation Phase I clinical trial to evaluate the safety and the tolerability of HLX10-HLX04 combination therapy in patients with advanced solid tumors after failure of standard of care.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: HLX04 Drug: HLX10 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection (HLX10) in Combination With Recombinant Anti-VEGF Humanized Monoclonal Antibody Injection (HLX04) in Patients With Advanced Solid Tumors
Estimated Study Start Date : November 27, 2018
Estimated Primary Completion Date : September 27, 2019
Estimated Study Completion Date : December 27, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: HLX04+HLX10
HLX10, at three dose levels (1, 3, 10 mg/kg), to be intravenously injected once every two weeks; HLX04, at a fixed dose of 5 mg/kg, intravenously injected once every two weeks; Study drugs given in combination for up to 2 years or until the disease gets worse, whichever comes first.
Drug: HLX04
Recombinant Anti-VEGF Humanized Monoclonal Antibody Injection

Drug: HLX10
Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of HLX04 plus HLX10 in patients with advanced solid tumors [ Time Frame: 28 days ]
    The MTD is the dose with toxicity rate (estimated by isotonic regression) most approximate to the target one (30%).

  2. Dose Limiting Toxicity (DLT) of HLX04 plus HLX10 in patients with advanced solid tumors [ Time Frame: 28 days ]
    DLT is defined as the occurrence of the following adverse events (unless judged by the investigator to be definitely unrelated to HLX04 or HLX10) within Cycle 1 (i.e., from Cycle 1 Day 1 to Cycle 1 Day 28)


Secondary Outcome Measures :
  1. PK parameters of the HLX04 plus HLX10 therapy in patients with advanced solid tumors [ Time Frame: Day 1 of treatment up to 2 years ]
    Peak Plasma Concentration (Cmax) for single dose and multiple doses

  2. PK parameters of the HLX04 plus HLX10 therapy in patients with advanced solid tumors [ Time Frame: Day 1 of treatment up to 2 years ]
    Area under the plasma concentration versus time curve (AUC) for single dose and multiple doses

  3. Objective Response Rate (ORR) of HLX04 plus HLX10 in patients with advanced solid tumors [ Time Frame: Day 1 of treatment up to 2 years ]
    ORR determined by RECIST criteria

  4. Disease Control Rate (DCR) of HLX04 plus HLX10 in patients with advanced solid tumors [ Time Frame: Day 1 of treatment up to 2 years ]
    DCR determined by RECIST criteria

  5. Duration of Response (DOR) of HLX04 plus HLX10 in patients with advanced solid tumors [ Time Frame: Day 1 of treatment up to 2 years ]
    DOR determined by RECIST criteria

  6. Progression-Free Survival (PFS) of HLX04 plus HLX10 in patients with advanced solid tumors [ Time Frame: Day 1 of treatment up to 2 years ]
    PFS determined by RECIST criteria

  7. Overall Survival (OS) of HLX04 plus HLX10 in patients with advanced solid tumors [ Time Frame: Day 1 of treatment up to 2 years ]
    OS determined by RECIST criteria

  8. Immunogenicity [ Time Frame: Day 1 of treatment up to 2 years ]
    Anti-drug Antibody (ADA) Testing



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Age ≥18 years, male or female
  2. Patient with histologically or cytologically confirmed advanced malignant solid tumors who have failed standard of care, or has no standard-of-care therapy or are not suitable for standard of care at the present stage;
  3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1;
  4. Life expectancy greater than 3 months;
  5. Patient must have at least one measurable tumor lesion as defined by RECIST v1.1; the lesion concerned must not be a bone metastasis if only one target lesion is present;
  6. Has adequate organ functions;
  7. If the subject is a patient with hepatocellular carcinoma, Child-Pugh classification must be A.
  8. A qualified patient (male or female) of childbearing potential must agree to use reliable contraceptive methods (hormonal, or barrier method or abstinence) for the course of the study and through at least 6 months after the last dose; a female patient of childbearing potential must have negative blood pregnancy test within 7 days prior to enrollment;
  9. The subject must give his/her informed consent to this study prior to the trial, and voluntarily sign a written informed consent form.

Exclusion Criteria:

  1. Histopathological confirmed head and neck cancer or squamous-cell lung cancer, or bleeding tendency in the tumor lesion judged by the investigator;
  2. Has received antitumor therapy like radiotherapy, chemotherapy, targeted therapy, endocrinal therapy or immunotherapy, or other clinical study drug therapy within 4 months prior to the initial drug administration;
  3. Has received a surgical operation on major viscera or experienced apparent trauma within 4 weeks from the initial drug administration, or experienced subcutaneous venous access device implantation within 7 days;
  4. The adverse reactions which occurred in the previous antitumor treatment were not recovered to ≤ grade 1 based on CTCAE 4.03 assessment (except for hair loss);
  5. Evidences of metastatic lesion in the patient's central nervous system;
  6. Previously experienced ≥ grade 3 immune-related adverse event during immunotherapy;
  7. Active, or history of autoimmune disease which may relapse (for example, systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.);
  8. Currently having or have had interstitial lung disease;
  9. Uncontrollable active infection(s);
  10. History of immunodeficiency, including HIV antibody positive;
  11. Known active hepatitis B; or hepatitis C virus infections;
  12. Has bleeding tendency;
  13. History of severe cardiovascular diseases;
  14. Known gastrointestinal diseases as follows:

    Gastrointestinal perforation, abdominal fistula or abdominal abscess within 6 months before signing the informed consent; History of poorly controlled or recurrent inflammatory bowel disease; Active peptic ulcers, or > moderate esophageal varices;

  15. Known hypersensitivity to Bevacizumab, or other anti-PD-1, anti-PD-L1 monoclonal antibody agents;
  16. Pregnant or breastfeeding female.

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): NCT03757936


Contacts
Contact: Joanne Wang +86-021-33395800-6024 Joanne_wang@henlius.com

Locations
China
Shanghai East Hospital Not yet recruiting
Shanghai, China
Contact: Jin Li, MD       lijin@csco.org.cn   
Sponsors and Collaborators
Shanghai Henlius Biotech

Responsible Party: Shanghai Henlius Biotech
ClinicalTrials.gov Identifier: NCT03757936     History of Changes
Other Study ID Numbers: HLX10HLX04-001
First Posted: November 29, 2018    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 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
Bevacizumab
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents