Clinical trial NCT04854681: Phase 1 Trial of the TQB2928 Injection in Patients With Advanced Cancers
Official title: A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TQB2928 Injection in Patients With Advanced Solid Tumors or Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumors and Hematological Malignancies
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-04-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: TQB2928 is a promising new molecular entity that mediates blockade of CD47 and SIRPα and enhances the phagocytosis of cancer cells by macrophages. In preclinical in vivo models, TQB2928 was active against a wide range of solid tumors and hematologic malignancies. This is the first-in-human phase 1 trial of TQB2928 in patients with advanced solid tumors and hematological malignancies.


Eligibility criteria: Inclusion Criteria:

* 1. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.

  2. Histologically or cytologically confirmed, locally advanced unresectable or metastatic solid tumors, or hematological malignancies, or lymphoma.

  3. Solid tumors or hematological malignancies that failed from standard therapy, or lymphoma patients who have had at least two regimens of systemic therapy failures, or who refused other systemic therapy.

  4. At least 1 measurable lesion according to tumor-appropriate response criteria.

  5. Must have adequate organ and bone marrow function. 6. Resolved acute effects of any prior therapy to baseline severity or Grade ≤1 per CTCAE v5.0 except for AEs not constituting a safety risk by investigator judgment.

  7. Serum pregnancy test (for females of childbearing potential) negative within 7 days before enrollment.

  8. Male and female patients of childbearing potential and at risk for pregnancy must agree to use two highly effective method(s) of contraception throughout the study and for at least 90 days (180 days if required by local regulation) after the last dose of assigned treatment.

  9. Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.

Exclusion Criteria:

* 1. Patients with known symptomatic brain metastases requiring steroids. 2. Concurrent secondary malignancy. 3. Uncontrolled pleural effusion or pericardial effusion with clinical significance and requiring repeated drainage as assessed by the Investigators.

  4. Prior treatment with monospecific or bispecific antibodies or fusion proteins targeting CD47 or signal regulatory protein alpha (SIRPα).

  5. Therapeutic or experimental monoclonal antibodies within 28 days prior to enrollment.

  6. Immunosuppressive regimens involving systemic corticosteroids (except \<10 mg daily prednisone equivalent) within 14 days before the first dose of study treatment.

  7. Prior allogeneic hematopoietic stem cell transplant. 8. Major surgical procedure, laparoscopic procedure, open biopsy or significant traumatic injury within 28 days prior to enrollment.

  9. RBC transfusion dependence, defined as requiring more than 2 units of RBC transfusions during the 4-week period prior to screening. RBC transfusions are permitted during screening and prior to enrollment to meet the hemoglobin inclusion criteria.

  10. Vaccination within 4 weeks prior to enrollment except for administration of inactivated vaccines (for example, inactivated influenza vaccines) 11. Active and clinically significant bacterial, fungal or viral infection including tuberculosis, hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.

  12. History of hemolytic anemia or Evans syndrome within 3 months. 13. Autoimmune hemolytic anemia (AIHA) assessed by Positive Direct Antiglobulin Test (DAT).

  14. Autoimmune disorders (e.g., Crohn's Disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus) and other diseases that compromise or impair the immune system.

  15. Unstable or serious concurrent medical conditions in the previous 6 months. 16. Significant medical diseases or conditions, as assessed by the Investigators, that would substantially increase the risk-benefit ratio of participating in the study.

  17. Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs)
timeFrame: During the first 28 days
measure: Maximum tolerated dose (MTD)
timeFrame: During the first 28 days
Secondary outcomes:
measure: Number of patients with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From the time of informed consent signed through 90 days after the last dose
measure: Pharmacokinetics: Cmax
timeFrame: From the time of informed consent signed through 90 days after the last dose
measure: Pharmacokinetics: Cmin
timeFrame: From the time of informed consent signed through 90 days after the last dose
measure: Pharmacokinetics: Tmax
timeFrame: From the time of informed consent signed through 90 days after the last dose
measure: Pharmacokinetics: AUC
timeFrame: From the time of informed consent signed through 90 days after the last dose
measure: Pharmacokinetics: T1/2
timeFrame: From the time of informed consent signed through 90 days after the last dose
measure: Percentage of ADA positive patients
timeFrame: From the time of informed consent signed through 90 days after the last dose
measure: Objective Response Rate (ORR)
timeFrame: up to 2 years
measure: Disease control rate (DCR)
timeFrame: up to 2 years
measure: Duration of Response (DOR)
timeFrame: up to 2 years
measure: Progression-free survival (PFS)
timeFrame: up to 2 years
Other outcomes:
Locations:
Study officials:
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