Clinical Trials /

The Safety, Tolerability, and Initial Efficacy of HX009 in Patients With Advanced Malignancies

NCT04097769

Description:

This is a first-in-human, multicenter, open-label, multiple-dose Phase I study to investigate the safety, tolerability, and initial efficacy of HX009 in subjects with advanced malignant tumors. The study will consist of a dose-escalation and dose-finding component to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and to evaluate the preliminary antitumor activity of HX009.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: The Safety, Tolerability, and Initial Efficacy of HX009 in Patients With Advanced Malignancies
  • Official Title: A Phase I, First-in-Human Study Evaluating the Safety, Tolerability, and Initial Efficacy of HX009 in Patients With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: HX009-I-01
  • NCT ID: NCT04097769

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
HX009anti-PD-1/CD47 infusion proteinHX009

Purpose

This is a first-in-human, multicenter, open-label, multiple-dose Phase I study to investigate the safety, tolerability, and initial efficacy of HX009 in subjects with advanced malignant tumors. The study will consist of a dose-escalation and dose-finding component to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and to evaluate the preliminary antitumor activity of HX009.

Detailed Description

      The study will follow a 3+3 dose-escalation scheme enrolling cohorts of at least 3 subjects
      sequentially at escalating doses. During study treatment, subjects will receive HX009
      treatment via intravenous infusion once every 2 weeks. Dose escalation will continue until
      identification of an MTD or the maximum dose is reached. Dose-limiting toxicities (DLTs) will
      be assessed from the first dose of study treatment (Day 1) until 28 days later (Day 29).

      The study is divided into a screening period (28 days before first dose), treatment period
      (up to 24 months), and survival follow-up period. Safety will be evaluated throughout the
      study up until 90 (±7) days after the last dose of study treatment. Blood samples will be
      collected at regular intervals for pharmacokinetics (PK) and immunogenicity evaluation. Tumor
      evaluation (assessed by the Investigator in accordance with Response Evaluation Criteria in
      Solid Tumors Version 1.1 [RECIST 1.1] and immune RECIST [iRECIST]) to assess efficacy will
      start from the first dose and occur every 8 weeks in the first 12 months and every 12 weeks
      in the second 12 months and during the survival follow-up period.
    

Trial Arms

NameTypeDescriptionInterventions
HX009OtherStudy treatment: HX009 administered every 2 weeks (14 [±1] days) via intravenous infusion.
  • HX009

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female subject aged 18 to 70 years, inclusive.

          2. Eastern Cooperative Oncology Group performance status of 0 to 1.

          3. Histologically confirmed advanced malignant tumor that is refractory/relapsed to
             standard therapies, or for which no effective standard therapy is available, or the
             subject refuses standard therapy.

          4. At least 1 measurable tumor according to RECIST v1.1 (see Appendix 7 of the protocol).

          5. Life expectancy ≥12 weeks.

          6. A subject with a history of brain/meninges metastases who has received prior topical
             treatment (surgery/radiotherapy) before the start of the study and is clinically
             stable for at least 3 months is allowed (prior treatment with corticosteroids is
             permitted; however, if a subject requires systemic concomitant treatment with
             corticosteroids, they must be excluded).

          7. Adequate organ function, as indicated by the following laboratory values, within 14
             days before signing informed consent:

             Hematology

               -  Hemoglobin ≥100 g/L (no blood transfusion is allowed within 14 days before
                  signing informed consent)

               -  Absolute neutrophil count ≥1.5 × 109/L

               -  Platelet count ≥100 × 109/L Biochemistry

               -  Total bilirubin ≤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)

               -  Serum creatinine ≤1 × ULN

               -  Prothrombin time/international normalized ratio ≤1.5 × ULN or activated partial
                  thromboplastin time ≤1.5 × ULN (for subjects on anticoagulants, prothrombin time
                  or activated partial thromboplastin time must be within the normal range for
                  anticoagulants).

          8. Male subject: must agree to use contraception as detailed in Appendix 5 of this
             protocol during the treatment period and for at least 12 months after the last dose of
             the study treatment.

             Female subject: must not be pregnant; or must not be of childbearing potential as
             defined in in Appendix 5; or if of childbearing potential, must agree to use highly
             effective birth control methods during the study treatment period and for at least 12
             months after the last dose of the study treatment.

          9. Voluntarily agrees to participate by giving written informed consent and is willing
             and able to comply with protocol and scheduled visits.

        Exclusion Criteria:

          1. For subjects who have received prior anti-PD-1, anti-PD-L1, or anti-cytotoxic
             T-lymphocyte-associated antigen 4 (CTLA-4):

               -  Subjects must not have received anti-PD-1, anti-PD-L1, anti-CTLA-4, CD47, or any
                  other immunotherapy or immune-oncology agent within 4 weeks of the first dose
                  study treatment

               -  Subjects must not have experienced a toxicity that led to permanent
                  discontinuation of prior immunotherapy

               -  Any adverse events reported while receiving prior immunotherapy must have
                  completely resolved or resolved to Grade 1 prior to screening for this study.

          2. Prior malignancy active within the previous 2 years except for the tumor for which a
             subject is enrolled in the study and locally curable cancers that have been apparently
             cured, such as basal or squamous cell skin cancer, superficial bladder cancer or
             carcinoma in situ of the cervix or breast.

          3. Allergic to recombinant humanized anti-PD-1 monoclonal antibody drugs and their
             components.

          4. Receipt of any immunotherapy, or investigational anticancer therapy within 4 weeks
             prior to the first dose of study treatment; in the case of mAbs (for investigational
             use or immunotherapy), 6 weeks prior to the first dose of study treatment.

          5. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy (except for
             subjects with metastatic prostate cancer on androgen deprivation treatment eg,
             goserelin, leuprorelin) for cancer. Concurrent use of hormones for noncancer-related
             conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
             NOTE: Local treatment of isolated lesions for palliative intent is acceptable (eg, by
             local surgery or local radiotherapy).

          6. Radiation therapy (localized radiation therapy for therapeutic purpose is allowed)
             within 4 weeks of the first dose of study treatment.

          7. Female subject who is pregnant or lactating.

          8. Tests positive for human immunodeficiency virus, or has active hepatitis B virus or
             hepatitis C virus.

          9. Active, or history of, autoimmune disease (within the past 2 years) that may recur
             (eg, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,
             autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulitis, etc) or are
             at high risk (eg, receiving an immunosuppressive treatment for an organ transplant);
             however, subjects with the following are allowed to enroll:

               -  Type I diabetes that is stable after a fixed dose of insulin

               -  Only requiring hormone replacement therapy for autoimmune hypothyroidism

               -  Skin disease that does not require treatment such as eczema, rash that accounts
                  for <10% of the body surface, psoriasis without ophthalmic symptoms.

         10. Planning major surgery during the study including the screening period.

         11. Requiring systemic corticosteroids (dose equivalent to >10 mg prednisone/day) or other
             immunosuppressive drugs within 14 days before the first dose of study treatment or
             during the study. The following are allowed:

               -  Use of topical or inhaled glucocorticoids

               -  A brief course of corticosteroids (≤7 days) for prophylaxis or for treatment of
                  non autoimmune conditions.

         12. Active peptic ulcer, incomplete intestinal obstruction, active gastrointestinal
             bleeding, and perforation.

         13. Lung disease, interstitial lung disease or pneumonia, pulmonary fibrosis, acute lung
             disease, interstitial pneumonia, etc.

         14. Uncontrolled stable systemic diseases such as cardiovascular and cerebrovascular
             diseases, diabetes, high blood pressure, etc.

         15. History of infection with human immunodeficiency virus, or other acquired, congenital
             immunodeficiency disease, or history of organ transplantation, or history of stem cell
             transplantation.

         16. Current, or history of, tuberculosis or evidence of latent tuberculosis infection:
             positive QuantiFERON-TB Gold assessment at screening.

         17. Severe infections within 4 weeks before the first dose of study treatment, or active
             infections within 2 weeks before the first dose that require oral or intravenous
             antibiotics.

         18. Cancerous meningitis.

         19. Has received hematopoietic stimulating factors such as colony stimulating factor and
             erythropoietin within 2 weeks before the first dose of study treatment.

         20. Use of any live vaccines within 4 weeks before the first dose of study treatment.

         21. Any major surgery within 4 weeks before the first dose of study treatment (except for
             diagnostic surgery).

         22. A history of psychotropic substance abuse who is unable to quit or who has a history
             of mental disorders.

         23. Other severe, acute or chronic medical or psychiatric diseases or laboratory
             abnormalities that, in the Investigator's opinion, may increase the study-related
             risks or interfere with the interpretation of the findings.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The safety of HX009
Time Frame:up to 90 days after the last dose of study treatment.
Safety Issue:
Description:Adverse Events.

Secondary Outcome Measures

Measure:Time for Cmax (Tmax) of HX009
Time Frame:Approximately 2 years
Safety Issue:
Description:Time to reach HX009 maximum observed serum concentration.
Measure:Terminal Half-life (t½)of HX009
Time Frame:Approximately 2 years
Safety Issue:
Description:HX009 terminal half-life.
Measure:Area Under the Serum Concentration-time Curve (AUC)
Time Frame:Approximately 2 years
Safety Issue:
Description:HX009 area under the serum concentration-time curve .
Measure:Number of Participants With Positive Anti-Drug Antibody (ADA) of HX009
Time Frame:Cycles 1, 2, 3, 4, 5, 6, 7, 9, 13, and 17, and then every 8 cycles, Day 1: within 60 minutes before the start of the infusion(each cycle is 14 days)
Safety Issue:
Description:ADA blood samples were assayed for anti-HX009 antibodies.
Measure:Objective response rate(ORR) Per Investigator Assessment Using RECIST 1.1
Time Frame:Approximately 2 years
Safety Issue:
Description:The ORR, using RECIST 1.1 criteria, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on Investigator assessment.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Waterstone Hanxbio Pty Ltd

Last Updated