Clinical Trial of the TQB2102 Injection in Patients With Advanced Cancers

Study Overview
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Brief Summary
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TQB2102 is an antibody-drug conjugate comprised of a humanised antibody against Human Epidermal Growth Factor Receptor 2 (HER2), a enzyme-cleavable linker, and a topoisomerase I inhibitor payload, which combine the ability of antibodies to specifically target tumour cells with the highly potent killing activity of drugs with payloads too toxic for systemic administration. This is a phase I study to evaluate the safety, tolerability and effectiveness of TQB102 injection in subjects with advanced malignancies.

Official Title
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A Phase I Study of TQB2102 Injection in Patients With Advanced Cancers

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: TQB2102 injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study; Male or female patient 18 to 75 years of age, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, and life expectancy ≥12 weeks; Histologically or cytologically confirmed, locally advanced tumors, Priority will be given to subjects with HER2 positive solid tumor; Malignant tumor that failed from standard treatment or had no standard treatment; According to the RECIST 1.1 standard, patient with at least one evaluable lesion; The main organs function well; Male or female patient had no plans to become pregnant and voluntarily took effective contraceptive measures from agree with the study to at least 6 months after the last dose of study drug. Exclusion Criteria: Concurrent secondary malignancy or other malignancy with no evidence of disease for more than 3 years; History of uncontrolled intercurrent illness; Major surgical procedure, radiotherapy, chemotherapy, or immunotherapy within 4 weeks prior to first dose; Patients with known symptomatic brain metastases; Receiving any other investigational agent within 4 weeks before first dose; Patients with severe hypersensitivity after the use of monoclonal antibodies History of interstitial lung disease or pneumonia; Unstable or serious concurrent medical conditions, as assessed by the Investigators, that would substantially increase the risk-benefit ratio of participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: TQB2102 injection<br>intravenous infuse TQB2102 injection every three weeks, 21 days as a treatment cycle. (1.5mg/kg, 3mg/kg, 4.5mg/kg, 6mg/kg, 7.5mg/kg, 9mg/kg) | Drug: TQB2102 injection<br>* TQB2102 is an antibody-drug conjugate comprised of a humanised antibody against HER2, a enzyme-cleavable linker, and a topoisomerase I inhibitor payload.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) | DLT was defined as toxicities that meet pre-defined severity criteria (according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) toxicity assessment criteria), and assessed as having a suspected relationship to study drug that occurred within the first cycle (21 days) of treatment. | During the first treatment cycle (21 days). | 
| Maximum tolerated dose (MTD) | MTD was defined as the highest dose at which dose-limiting toxicity (DLT) occurred in less than 33% of patients. | During the first treatment cycle (21 days). | 
| The occurrence rate of all adverse events (AEs) | The occurrence of adverse events defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) | From date of the first dose until 28 days after last dose or new anti-tumor treatment, whichever came first. | 
| The severity of all adverse events (AEs) | The severity of adverse events defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) | From date of the first dose until 28 days after last dose or new anti-tumor treatment, whichever came first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | Incidence of anti-drug antibody (ADA) | Before infusion on Cycle1 Day1, Cycle2 Day1, Cycle 4 Day1, Cycle7 Day1, Cycle12 Day1 (each cycle is 21 days). 90 days after the end of the last infusion. | 
| Area under the curve (AUC) | The area under the curve (AUC) of serum or plasma concentration of ADC drug, total antibody, and small molecule toxin. | Before infusion, 15 minutes after infusion on Cycle1 Day1, Cycle2 Day1, Cycle3 Day1, Cycle4 Day1 and Cycle6 Day1; 4hours, 7 hours, 7days and 14days after infusion on Cycle1 Day1; 4 hours and 7 hours after infusion on Cycle3 Day1. each cycle is 21 days | 
| Peak concentration (Cmax) | Maximum observed concentration (Cmax) of ADC drug, total antibody, and small molecule toxin. | Before infusion, 15 minutes after infusion on Cycle1 Day1, Cycle2 Day1, Cycle3 Day1, Cycle4 Day1 and Cycle6 Day1; 4 hours, 7 hours, 7days and 14days after infusion on Cycle1 Day1; 4 hours and 7 hours after infusion on Cycle3 Day1. each cycle is 21 days | 
| Terminal half-life (T1/2) | Terminal plasma half-life is the time required to divide the plasma concentration by two. | Before infusion, 15 minutes after infusion on Cycle1 Day1, Cycle2 Day1, Cycle3 Day1, Cycle4 Day1 and Cycle6 Day1; 4 hours, 7 hours, 7days and 14days after infusion on Cycle1 Day1; 4 hours and 7 hours after infusion on Cycle3 Day1. each cycle is 21 day | 
| Objective Response Rate (ORR) | Defined as the percentage of Complete Response (CR) plus partial response (PR) assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria | Baseline up to 2 years. | 
| Disease control rate (DCR) | Defined as the proportion of subjects with CR, PR, or SD (Stable Disease). | Baseline up to 2 years. | 
| Duration of Response (DOR) | Defined as the time from first documented response to documented disease progression. | Baseline to the date of documented disease progression, up to 2 years. | 
| Progression-free survival (PFS) | Defined as the time from first documented response to documented disease progression. | Baseline to the date of documented disease progression, up to 2 years. | 
| Overall survival(OS) | Overall survival refers to the time from the first treatment to death from any cause. | Baseline to the date of death from any cause, up to 2 years. |