A Study Evaluating the Safety, Tolerance and Anti-tumor Activity of a Study Drug in Subjects With Advanced Solid Tumors

Overview

This is a study to evaluate the safety and tolerability of the study drug HBM4003, and to determine the maximum tolerated dose and/or recommended Phase 2 study dose of HBM4003. Participants will receive 3 escalating doses of HBM4003, with the possibility of a fourth, higher dose level following review by a Safety Committee. The study will also look at the anti-tumor activity of HBM4003.

Full Title of Study: “A Phase 1 Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of HBM4003 in Subjects With Advanced Solid Tumors”

Study Type

  • Study Type: Interventional
  • Study Design
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 2020

Interventions

  • Drug: HBM4003
    • Intravenous (IV) administration on days 1, 8, 15 and 22 of a 28-day treatment cycle.

Arms, Groups and Cohorts

  • Experimental: HBM4003
    • Up to 4 (28 day) cycles of treatment with the potential for a higher dose to be administered in each of cycle 2 and cycle 4.

Clinical Trial Outcome Measures

Primary Measures

  • Proportion of subjects with Dose-Limiting Toxicity (DLT)
    • Time Frame: From Day 1 until disease progression or Day 28
    • Number of subjects who experience DLT events during 28 days after first administration of HBM4003, divided by the number of DLT-evaluable subjects

Secondary Measures

  • Objective Response Rate
    • Time Frame: Up to 28 months
    • Proportion of subjects with best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 and per Response Criteria for Use in Trials Testing Immunotherapeutics (iRECIST)
  • Duration of response
    • Time Frame: Up to 28 months
    • Time interval from first occurrence of a documented objective response to the time of disease progression, as determined by the Investigator using RECIST 1.1 or death from any cause, whichever comes first.
  • Disease control rate
    • Time Frame: Up to 28 months
    • Proportion of subjects with a best overall response of complete response (CR), partial response (PR) or stable disease (SD).
  • Duration of disease control
    • Time Frame: Up to 28 months
    • Time from data of start of treatment to the date of disease progression or death for subjects who had CR or PR or SD during treatment.
  • Tumor shrinkage (The percentage of patients with tumor shrinkage)
    • Time Frame: Up to 28 months
    • Greatest tumor shrinkage achieved at any follow-up assessment. Measured by radiological (computed tomography [CT]/Magnetic Resonance Imaging [MRI]) scanning until documented radiographic disease progression according to RECIST 1.1, or loss of clinical benefit after disease progression according to RECIST 1.1
  • Cmax (Maximum serum concentration)
    • Time Frame: Up to 28 months
  • Tmax (Time to reach maximum serum concentration)
    • Time Frame: Up to 28 months
    • Plasma
  • AUC0-tau (Area under the serum concentration versus time curve from time zero to the dosing interval tau
    • Time Frame: Up to 28 months
  • AUC0-inf (Area under the serum concentration versus time curve from time zero to infinity
    • Time Frame: Up to 28 months
  • t1/2 (Terminal half-life)
    • Time Frame: Up to 28 months
  • Clearance (CL)
    • Time Frame: Up to 28 months
  • Vss (Volume of distribution at steady state)
    • Time Frame: Up to 28 months

Participating in This Clinical Trial

Inclusion Criteria

  • Signed informed consent form and willingness to comply study requirements.
  • Confirmed advanced solid tumors that have progressed after treatment with standard therapies, or for which no effective standard therapy is available, or the subject refuses or has a contraindication to standard therapy.
  • Adequate organ and bone marrow function.
  • Females of childbearing potential may participate provided they agree to practice abstinence; and, if heterosexually active, agree to use at least 2 highly effective contraceptive methods throughout the study and for 3 months following the last dose of study drug; and have a negative serum pregnancy test.
  • Females of non-childbearing potential must be post-menopausal or have been surgically sterilized.
  • Male subjects with a female partner of childbearing potential must agree to practice abstinence or to use a physician-approved contraceptive method throughout the study and for 3 months following the last does of study drug.

Exclusion Criteria

  • Participation in another clinical study at the same time.
  • History of severe allergic diseases, history of severe drug allergy, or are known to be allergic to macromolecular protein preparations or any component of the study drug.
  • Receipt of anticancer medications or investigational drugs within the following intervals before the first administration of the study drug:

1. CTLA-4 antibody within 6 weeks of study drug administration;

2. Any PD-1 or PD-L1 or Programmed cell death protein ligand 2 (PDL2)-directed antibody within 4 weeks of study drug administration;

3. Any other anticancer therapy within 2 weeks of the start of the study;

4. Anti-tumor vaccines within 3 months prior to study drug administration;

5. Live vaccine within 4 weeks prior to study drug administration or planned live vaccine during study period;

6. Corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 2 weeks of study drug administration; Nasal spray, inhalation, topical corticosteroids or physiological doses of systemic corticosteroids are not included.

  • Major surgical procedure(s) within 28 days prior to first dose of study drug.
  • Failure to recover from any immune-related toxicity from prior cancer therapy, or any other toxicity related to previous anticancer treatment, with the exception of alopecia.
  • Combination medication or treatments to be excluded:

1. Any concurrent chemotherapy, radiotherapy, immunotherapy, or biological therapy for cancer treatment. Concurrent use of hormones on a stable dose for non-cancer related conditions is acceptable. Androgen deprivation therapy (ADT) for advanced prostate cancers is acceptable. Local treatment of isolated non-target lesions for palliative intent is acceptable;

2. Any traditional anti-tumor herbal medications;

3. Receipt of red blood cells or platelets infusion, granulocyte colony stimulating factor (G-CSF) or granulocyte monocyte colony stimulating factor (GM-CSF) within 1 week of the first dose of study drug.

  • Have other diseases that may affect the effectiveness and safety of the study drug, such as:

1. Known brain metastases or other central nervous system metastases that is either symptomatic or untreated, that requires concurrent treatment;

2. Active infection requiring treatment of antibiotics within 14 days prior to first dose of study drug;

3. Known history of infection of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS), human T lymphotropic virus 1, hepatitis B virus, or active hepatitis C virus;

4. Active known or suspected autoimmune disease or a history of autoimmune disease, including but not limited to inflammatory bowel disease, autoimmune hepatitis, Guillain-Barre syndrome.

5. Known primary immunodeficiency;

6. Sever diarrhea, active gastrointestinal bleeding, or a history of Gastrointestinal perforation, acute diverticulitis, intra-abdominal abscess or gastrointestinal obstruction;

(b) Have received allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation, or have received autologous hematopoietic stem cell transplantation within 3 months prior to the first dose of study drug.

  • Subjects with major cardiovascular disease.
  • History of other uncured malignant diseases, except for non-melanoma skin cancer in situ, superficial bladder cancer, cervical cancer in situ that has been curatively resected, and localized prostate cancer managed by active surveillance.
  • Pregnant or breastfeeding women.

Other protocol-defined inclusion/exclusion criteria may apply.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Harbour BioMed (Guangzhou) Co. Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Maria, +86 021-5339-9017, maria.deassis@harbourbiomed.com

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