Phase 1 Trial of the TQB2928 Injection in Patients With Advanced Cancers

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TQB2928 Injection in Patients With Advanced Solid Tumors or Hematological Malignancies

Conditions
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Advanced Solid Tumors and Hematological Malignancies

Intervention / Treatment
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* Drug: TQB2928 Injection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQB2928 injection<br>Dose Escalation: intravenous (IV) infusion of TQB2928 as monotherapy | Drug: TQB2928 Injection<br>* 4 weekly IV infusions (Days 1, 8, 15, and 22) of TQB2928 in each 28-day treatment cycle until unacceptable toxicity, documentation of confirmed progressive disease (PD), or subject withdrawal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLTs) | DLTs will be assessed during the first 28 days of treatment for dose-escalation and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle (28 days) of treatment. | During the first 28 days | 
| Maximum tolerated dose (MTD) | MTD is defined as the highest dosing schedule cohort level at which no more than 1 of 6 patients experience a Dose Limiting Toxicity (DLT). | During the first 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events (AEs) and serious adverse events (SAEs) | Assessed by CTCAE v5.0 | From the time of informed consent signed through 90 days after the last dose | 
| Pharmacokinetics: Cmax | Maximum observed concentration (Cmax) of TQB2928 after administration | From the time of informed consent signed through 90 days after the last dose | 
| Pharmacokinetics: Cmin | Minimum observed concentration (Cmin) of TQB2928 at steady state | From the time of informed consent signed through 90 days after the last dose | 
| Pharmacokinetics: Tmax | Time to maximum concentration (Tmax) | From the time of informed consent signed through 90 days after the last dose | 
| Pharmacokinetics: AUC | The area under the curve (AUC) of serum concentration of TQB2928 | From the time of informed consent signed through 90 days after the last dose | 
| Pharmacokinetics: T1/2 | Terminal half-life (T1/2) | From the time of informed consent signed through 90 days after the last dose | 
| Percentage of ADA positive patients | Number of patients who develop detectable anti-drug antibody (ADA), and percentage of ADA positive patients will be calculated to evaluate immunogenicity of TQB2928. | From the time of informed consent signed through 90 days after the last dose | 
| Objective Response Rate (ORR) | Defined as the percentage of Complete Response (CR) plus partial response (PR) assessed by iRECIST v1.1 criteria for solid tumors, Lugano2014 criteria and lymphoma response to immunomodulatory therapy criteria (LYRIC) for lymphoma, and AML IWG 2003 response criteria for acute myeloid leukemia (AML). | up to 2 years | 
| Disease control rate (DCR) | Defined as the proportion of subjects with CR, PR, or SD. | up to 2 years | 
| Duration of Response (DOR) | Defined as the time from first documented response to documented disease progression. | up to 2 years | 
| Progression-free survival (PFS) | Defined as the time from the first dose of TQB2928 to the first occurrence of disease progression or death from any cause. | up to 2 years |