BAT7104 in Patients With Advanced Solid Tumours

Study Overview
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Brief Summary
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This is a prospective multi-centre, Open-Label Study to Assess Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of BAT7104 in Patients with Advanced Solid Tumours in Australia.

Official Title
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A Phase 1, Multi-Center, Open-Label Study to Assess Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of BAT7104 in Patients With Advanced Solid Tumours

Conditions
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Patients With Advanced Solid Tumors

Intervention / Treatment
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* Biological: BAT7104


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to give voluntary informed consent and understand the study and are willing to follow and complete all the study required procedures. Aged ≥ 18 years Life expectancy ≥ 3 months. Eastern Cooperative Oncology Group （ECOG）performance status ≤ 1. Histologically/cytologically confirmed, locally advanced unresectable or metastatic solid tumours that are refractory to standard therapy, or for whom no standard therapy exists, and where standard therapy is contraindicated or has been declined by the patient. Note that certain malignancies can be included based on imaging (e.g., HCC) and can be included based on the discretion of the PI, Sponsor Medical Monitor approval. Has measurable or evaluable disease per RECIST v1.1. that was not in a prior radiation or other locally treated area, unless imagingbased progression has been clearly documented following radiation or other local therapy. Adequate haematological, liver, and kidney function International normalized ratio (INR) /prothrombin time (PT)< 2, activated partial thromboplastin time (aPTT) ≤ 1.5 × upper limits of normal （ULN）. Must agree to adhere to the current state and national advice regarding minimising exposure to COVID-19 from the first Screening visit until the end of study (90-day follow-up) visit. Exclusion Criteria: Females who are pregnant or nursing; Receiving concurrent anticancer therapy or investigational therapy (including chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy); Has remaining AEs > Grade 1 from prior antitumour treatment as per CTCAE v5.0, with the exception of alopecia or ≤ Grade 2 peripheral neuropathy. Patients with chronic Grade 2 toxicities may be eligible per discretion of the Investigator or designee and Sponsor Medical Monitor (e.g., Grade 2 chemotherapy induced neuropathy). Patients with primacy central nervous system (CNS) malignancy, symptomatic CNS metastases, meningeal metastases or leptomeningeal disease are not allowed. Note: Patients with asymptomatic CNS metastases are eligible if clinically controlled, which is defined as 1) ≥4 weeks of stable neurologic function following CNSdirected therapy prior to Cycle 1 Day 1 dosing, 2) no evidence of CNS disease progression as determined by radiographic imaging ≥ 4 weeks prior to Cycle 1 Day 1 dosing, 3) ≥ 2 weeks from discontinuation of anti-seizure and steroid therapies (receiving prednisone ≤ 10mg or equivalent steroid therapies is allowed) prior to Cycle 1 Day 1 dosing. Had major surgery within 28-days of the Screening visit. Note: Patients who have undergone a surgical procedure ≥ 28-days prior to Screening must have recovered adequately from the toxicity and/or complications from the intervention before the first dose of study drugs. Exception: no waiting period applies following port-a-cath placement for venous access. History of tissue or organ transplantation. History of severe infection deemed clinically significant by the PI or designee within 4 weeks or signs and symptoms of any active infection within 2 weeks prior to the first dose of study drugs. History of human immunodeficiency virus (HIV) infection or history of autoimmune diseases. Active hepatitis B or C. History of a Grade 3 or Grade 4 allergic reaction to treatment with another monoclonal antibody.

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Dose 0.3mg/kg | Biological: BAT7104<br>* Symmetric IgG-like AntiPD-L1/CD47 Bispecific Antibody Solution for Injection BAT7104 injection available in 100 mg/2 mL (50 mg/mL) dosage<br>|
| Experimental: Cohort 2<br>Dose 1mg/kg | Biological: BAT7104<br>* Symmetric IgG-like AntiPD-L1/CD47 Bispecific Antibody Solution for Injection BAT7104 injection available in 100 mg/2 mL (50 mg/mL) dosage<br>|
| Experimental: Cohort 3<br>Dose: 3 mg/kg | Biological: BAT7104<br>* Symmetric IgG-like AntiPD-L1/CD47 Bispecific Antibody Solution for Injection BAT7104 injection available in 100 mg/2 mL (50 mg/mL) dosage<br>|
| Experimental: Cohort 4<br>Dose: 10 mg/kg | Biological: BAT7104<br>* Symmetric IgG-like AntiPD-L1/CD47 Bispecific Antibody Solution for Injection BAT7104 injection available in 100 mg/2 mL (50 mg/mL) dosage<br>|
| Experimental: Cohort 5<br>Dose: 20 mg/kg | Biological: BAT7104<br>* Symmetric IgG-like AntiPD-L1/CD47 Bispecific Antibody Solution for Injection BAT7104 injection available in 100 mg/2 mL (50 mg/mL) dosage<br>|
| Experimental: Cohort 6<br>Dose: 40 mg/kg | Biological: BAT7104<br>* Symmetric IgG-like AntiPD-L1/CD47 Bispecific Antibody Solution for Injection BAT7104 injection available in 100 mg/2 mL (50 mg/mL) dosage<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Number of subjects who experience DLT events during 28 days. Toxicity will be graded according to CTCAE, Version 5.0. | A minimum of 28 days after first dose of BAT-7104 | 
| Adverse Events (AEs) | Incidence of treatment -related AEs as assessed by CTCAE, Version 5.0. | up to 90 days after the last dose, an average of 1 year | 
| Serious adverse events (SAEs) | Any SAE that is judged by the PI or designee to be related to the study medication must be reported regardless of the amount of time since the last dose received. Follow-up information collected for any initial report of an SAE must also be reported to the Sponsor (or its designee) within 24 hours of receipt by the PI or designee. | From the time of informed consent to 90 days after the last dose, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (Maximum serum concentration) | Maximum observed plasma or serum concentration | up to Cycle 6, each cycle is 14 days | 
| Presence of anti-drug antibodies (ADAs) / neutralizing antibodies (NAbs) |  | up to Cycle 6, each cycle is 14 days | 
| Objective response rate (ORR) | The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1. | 12 months (anticipated) | 
| Tmax (Time to reach maximum serum concentration) | Time to Maximum concentration | up to Cycle 6, each cycle is 14 days | 
| AUC0-inf after Cycle 1 administration and AUC0- λ after Cycle 6 administration | area under the serum concentration versus time curve from time zero to infinity and to time λ | up to Cycle 6, each cycle is 14 days | 
| Systemic Clearance (CL) | Systemic dose clearance | up to Cycle 6, each cycle is 14 days | 
| Vss (volume of distribution at steady state) | Amount of drug in the body divided by plasma concentration | up to Cycle 6, each cycle is 14 days | 
| t1/2 (terminal half-life) | Apparent terminal-phase disposition half-life. | up to Cycle 6, each cycle is 14 days |