A Study of TQB2102 for Injection in Patients With Recurrent/Metastatic Breast Cancer

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), an 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 1/Phase 2 study to evaluate the effectiveness, safety, pharmacokinetics (PK) and anti-drug antibody (ADA) of TQB2102 for injection in subjects with HER2-expressing relapsed/metastatic breast cancer.

Official Title
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A Phase 1 Clinical Trial of TQB2102 for Injection in Patients With Human Epidermal Growth Factor Receptor 2 (HER2) -Expressing Relapsed/Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: TQB2102 for injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects voluntarily participate in this study and sign informed consent; Between the ages of 18-75 years (subject to the date of signing the informed consent); Eastern cooperative oncology group (ECOG) score 0-1; estimated survival time ≥3 months; Breast cancer patients diagnosed with HER2 expression by pathological examination, with evidence of local focal recurrence or distant metastasis, are not suitable for surgery or radiotherapy for cure; Disease progression or intolerance during or after the most recent treatment period must be present before participating in clinical trials; At least one measurable lesion (based on Response Evaluation Criteria In Solid Tumors 1.1); The main organs function are normally; Female participants of childbearing age should agree to use contraception during the study period and for 6 months after the end of the study; Have a negative serum pregnancy test within 7 days prior to study enrollment and must be a non-lactating subject; Male participants should agree that contraception must be used during the study period and for 6 months after the end of the study period. Exclusion Criteria: Concomitant disease and medical history: Has diagnosed and/or treated additional malignancy within 3 years prior to first administration of study drug; Adverse effects due to any prior treatment have not been restored according to CommonTerminology Criteria for Adverse Events (CTCAE) 5.0 ≤ level 1 (Excluding hair loss); Major surgical treatment, incision biopsy, or significant traumatic injury received within 28 days prior to study treatment; Long-term unhealed wounds or fractures; Patients who have a prior history of interstitial lung disease/pneumonia requiring steroid intervention, or who are present with interstitial lung disease/pneumonia, or who are suspected of having interstitial lung disease/pneumonia on screening imaging and cannot be ruled out; Arterial/venous thrombosis events, such as cerebrovascular accident, deep vein thrombosis, and pulmonary embolism, occurred within 6 months before the first medication; Patients who have a history of psychotropic substance abuse and are unable to abstain or have mental disorders; Patients with any severe and/or uncontrolled disease; Tumor related symptoms and treatment: Patients who have been treated with other antitumor drug, such as chemotherapy, radical radiotherapy, or immunotherapy, within 4 weeks prior to the first dose, or who are still within 5 half-lives of the drug; Received Chinese patent drugs with anti-tumor indications specified in the National Medical Products Administration (NMPA) approved drug instructions within 2 week before the study treatment; Patients whose imaging shows that the tumor has invaded important blood vessels or who are determined by the investigators to be highly likely to invade important blood vessels during follow-up studies and cause fatal major bleeding; Uncontrolled pleural effusion, ascites, and moderate or higher pericardial effusion requiring repeated drainage; Known presence of cancerous meningitis or clinically active central nervous system metastasis; Patients who have been stable for at least 4 weeks after treatment and have been off corticosteroids for at least 2 weeks are excluded; Patients with severe bone injury due to tumor bone metastasis; Study treatment related: people who are known to be allergic to the study drug or its excipients, or to humanized monoclonal antibody products; Patients who participated in and used other anti-tumor clinical trials within 4 weeks before the first medication; In the judgment of the investigator, there is a situation that seriously endangers the safety of the subjects or affects the completion of 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 for injection<br>Dose: 6.0 mg/kg or 7.5 mg/kg of TQB2102 for injection. Administration: Intravenous infusion, administered every 3 weeks, 21 days as a treatment cycle. | Drug: TQB2102 for injection<br>* TQB2102 for injection is a HER2 dual-antibody-drug Conjugate (ADC)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR defined as percentage of participants achieving complete response (CR) and partial response (PR). | Baseline up to 10 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS defined as the time from the first injection until the first documented progressive disease (PD) or death from any cause, whichever happens first. | Baseline up to 14 months. | 
| Duration of Remission (DOR) | DOR defined as the time when the participants first achieved complete or partial remission to disease progression. | Baseline up to 14 months. | 
| Disease Control Rate (DCR) | Percentage of participants achieving complete response (CR), partial response (PR) and stable disease (SD). | Baseline up to 10 months. | 
| Clinical Benefit Rate (CBR) | Percentage of participants achieving complete response (CR), partial response (PR) and stable disease (SD) for ≥ 24 weeks. | Baseline up to 14 months. | 
| Overall Survival (OS) | OS defined as the time from the first injection to death from any cause. | Baseline up to 20 months. | 
| Incidence of adverse event (AE) | The occurrence of all adverse medical events after the first injection. | From the date of signing the informed consent to 28 days after the last dosing or a new anti-tumor treatment, whichever comes first. | 
| Severity of adverse event (AE) | The severity of all adverse medical events after the first injection. | From the date of signing the informed consent to 28 days after the last dosing or a new anti-tumor treatment, whichever comes first. | 
| Concentration of TQB2102 | Serum concentration of TQB2102 | 0 to 1 hour before infusion and 0.5 to 2 hours after infusion on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Cycle 7 Day 1. Each cycle is 21 days. | 
| Concentration of total antibody | Total antibody concentration in serum | 0 to 1 hour before infusion and 0.5 to 2 hours after infusion on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Cycle 7 Day 1. Each cycle is 21 days. | 
| Small molecule toxin | Small molecule toxin in plasma | 0 to 1 hour before infusion and 0.5 to 2 hours after infusion on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 and Cycle 7 Day 1. Each cycle is 21 days. | 
| Anti-drug antibody (ADA) | Incidence of anti-drug antibody (ADA) | Before infusion on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 7 Day 1, Cycle 12 Day 1, 30 days after the end of the last infusion. Each cycle is 21 days. |