Assess Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of BAT8009

Study Overview
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Brief Summary
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Primary objectives: To evaluate the safety and tolerability of BAT8009 in patients with advanced solid tumours. To determine the maximum tolerated dose (MTD) and recommended dose for Phase 2 (RP2D).

Detailed Description
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This is a first-in-human (FIH), multicentre, open-label, Phase 1 dose escalation and dose expansion study of BAT8009 (a B7H3-targeting antibody-drug conjugate) in patients with advanced solid tumours.

Official Title
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A Phase 1, Multi-Center, Open-Label Study to Assess Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of BAT8009 in Patients With Advanced Solid Tumours

Conditions
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Locally Advanced/Metastatic Solid Tumours

Intervention / Treatment
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* Drug: BAT8009 for Injection


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 and ≤ 75 years. Life expectancy ≥ 3 months. ECOG performance status ≤ 1. Histologically/cytologically confirmed, locally advanced unresectable or metastatic solid tumours that are refractory to standard therapy. Has measurable or evaluable disease per RECIST v1.1. Adequate haematological, liver, kidney, cardiac and coagulation function. Is willing to provide pre-existing diagnostic or resected tumour samples (if available). Female patients must: Be of non-child-bearing potential; Male patients must: be willing not to donate sperm. 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 (28-day Safety Follow-up Visit). Exclusion Criteria: Females who are pregnant or nursing. Receiving concurrent anticancer therapy or investigational therapy. Persisting AEs that are > Grade 1 from prior antitumour treatment as per CTCAE v5.0. Patients with primacy central nervous system (CNS) malignancy, symptomatic CNS metastases, meningeal metastases or leptomeningeal disease are not allowed. Had major surgery within 28 days of the Screening visit. History of autologous transplantation ≤ 3 months. History of severe infection deemed clinically significant by the PI or designee within 4 weeks. History of human immunodeficiency virus (HIV) infection. Active hepatitis B or C. History of a Grade 3 or Grade 4 allergic reaction to treatment with other antibodies.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Experimental: BAT8009 for Injection 0.6 mg/kg (frequency: Q3W) | Drug: BAT8009 for Injection<br>* BAT8009 will be administered as a 90-minute (± 5min) IV infusion on Day 1 of Cycle 1. If there is no infusion related reaction after initial dose, the next dose of BAT8009 will be infused intravenously into each patient for approximately 30 120 minutes.<br>* Other names: Recombinant Humanized Anti-B7H3 Monoclonal Antibody-Exatecan Conjugate;|
| Experimental: Cohort 2<br>Drug: BAT8009 for Injection 1.2 mg/kg (frequency: Q3W) | Drug: BAT8009 for Injection<br>* BAT8009 will be administered as a 90-minute (± 5min) IV infusion on Day 1 of Cycle 1. If there is no infusion related reaction after initial dose, the next dose of BAT8009 will be infused intravenously into each patient for approximately 30 120 minutes.<br>* Other names: Recombinant Humanized Anti-B7H3 Monoclonal Antibody-Exatecan Conjugate;|
| Experimental: Cohort 3<br>Drug: BAT8009 for Injection 2.4 mg/kg (frequency: Q3W) | Drug: BAT8009 for Injection<br>* BAT8009 will be administered as a 90-minute (± 5min) IV infusion on Day 1 of Cycle 1. If there is no infusion related reaction after initial dose, the next dose of BAT8009 will be infused intravenously into each patient for approximately 30 120 minutes.<br>* Other names: Recombinant Humanized Anti-B7H3 Monoclonal Antibody-Exatecan Conjugate;|
| Experimental: Cohort 4<br>Drug: BAT8009 for Injection 3.6mg/kg (frequency: Q3W) | Drug: BAT8009 for Injection<br>* BAT8009 will be administered as a 90-minute (± 5min) IV infusion on Day 1 of Cycle 1. If there is no infusion related reaction after initial dose, the next dose of BAT8009 will be infused intravenously into each patient for approximately 30 120 minutes.<br>* Other names: Recombinant Humanized Anti-B7H3 Monoclonal Antibody-Exatecan Conjugate;|
| Experimental: Cohort 5<br>Drug: BAT8009 for Injection 4.8mg/kg (frequency: Q3W) | Drug: BAT8009 for Injection<br>* BAT8009 will be administered as a 90-minute (± 5min) IV infusion on Day 1 of Cycle 1. If there is no infusion related reaction after initial dose, the next dose of BAT8009 will be infused intravenously into each patient for approximately 30 120 minutes.<br>* Other names: Recombinant Humanized Anti-B7H3 Monoclonal Antibody-Exatecan Conjugate;|
| Experimental: Cohort6<br>Drug: BAT8009 for Injection 6.0mg/kg (frequency: Q3W) | Drug: BAT8009 for Injection<br>* BAT8009 will be administered as a 90-minute (± 5min) IV infusion on Day 1 of Cycle 1. If there is no infusion related reaction after initial dose, the next dose of BAT8009 will be infused intravenously into each patient for approximately 30 120 minutes.<br>* Other names: Recombinant Humanized Anti-B7H3 Monoclonal Antibody-Exatecan Conjugate;|
| Experimental: Cohort 7<br>Drug: BAT8009 for Injection 7.2mg/kg (frequency: Q3W) | Drug: BAT8009 for Injection<br>* BAT8009 will be administered as a 90-minute (± 5min) IV infusion on Day 1 of Cycle 1. If there is no infusion related reaction after initial dose, the next dose of BAT8009 will be infused intravenously into each patient for approximately 30 120 minutes.<br>* Other names: Recombinant Humanized Anti-B7H3 Monoclonal Antibody-Exatecan Conjugate;|
| Experimental: Cohort 8<br>Drug: BAT8009 for Injection 8.4mg/kg (frequency: Q3W) | Drug: BAT8009 for Injection<br>* BAT8009 will be administered as a 90-minute (± 5min) IV infusion on Day 1 of Cycle 1. If there is no infusion related reaction after initial dose, the next dose of BAT8009 will be infused intravenously into each patient for approximately 30 120 minutes.<br>* Other names: Recombinant Humanized Anti-B7H3 Monoclonal Antibody-Exatecan Conjugate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity(DLT) | A DLT is defined as a toxicity occurring during the DLT observation period | A minimum of 21 days after first dose of BAT8009 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (Maximum serum concentration) | Maximum observed plasma or serum concentration | 126 days after first dosing | 
| Immunogenicity | Presence of ADAs / neutralizing antibodies (NAbs). | 126 days after first dosing | 
| 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 | 126 days after first dosing |