An Exploratory Clinical Study of BC006 in Patients With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This is a first in human, open-label, exploratory phase I clinical study including dose escalation (Ia) and dose expansion (Ib) stage. It aims to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of BC006 in giant cell tumor of tendon sheath (GCTTS) and other advanced solid tumors.

Official Title
-----------------
An Exploratory Clinical Study to Evaluate the Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of BC006 Monoclonal Antibody Injection in Patients With Advanced Solid Tumors Including Giant Cell Tumor of Tendon Sheath

Conditions
-----------------
Advanced Solid Tumors (Including GCTTS)

Intervention / Treatment
-----------------
* Drug: BC006


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Signed informed consent form. Age ≥ 18 years. Clinical diagnosis: Dose Escalation: Phase Ia Histologically or cytologically confirmed GCTTS: initial treatment unresectable, or postoperative recurrence unresectable, or refuse surgical treatment. Patients with histologically or cytologically confirmed advanced solid tumor, who have progression after prior SOC therapy, or who intolerant to SOC, or for whom there is no SOC therapy available. Dose Expansion: Phase Ib Cohort 1: Histologically or cytologically confirmed GCTTS: initial treatment unresectable, or postoperative recurrence unresectable, or refuse surgical treatment. Cohort 2 4: Patients with histologically or cytologically confirmed advanced solid tumor which is sensitive to Ia treatment，who have progression after prior SOC therapy, or who intolerant to SOC, or for whom there is no SOC therapy available. Life expectancy ≥ 12 weeks. Ia: at least one evaluable lesion; Ib: at least one measureable lesion as defined by RECIST V1.1. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. Evidence of adequate organ function by standard laboratory tests: Adequate hematological function: Hemoglobin (Hgb) ≥ 90 g/L, Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, Platelets (Plts) ≥ 90 × 109/L. Adequate liver function: Total bilirubin ≤ 1.5 × the upper limit of normal (ULN), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) ≤ 2.5 × ULN (AST≤ 5 × ULN, ALT≤ 5 × ULN for subjects with liver metastases). Adequate renal function: Creatinine ≤ 1.5 × ULN, or Creatinine clearance by Cockcroft Gault formula ≥ 50 mL/min. Adequate Coagulation function: Activated partial thrombin time (APTT) ≤ 1.5 × ULN, prothrombin time (PT) ≤ 1.5 × ULN, international standardized ratio (INR) ≤ 1.5 × ULN. Female patients of child-bearing potential or male patients with a female partner(s) of child-bearing potential must agree to use reliable contraceptive methods (hormonal, condoms or abstinence) for the duration of the study and for 6 months after the last dose of BC006; women of child-bearing potential must have a negative blood or urine pregnancy test within 7 days prior to enrollment. Key Exclusion Criteria: Prior anti-tumor therapies such as radiotherapy, chemotherapy, targeted therapy, endocrine therapy, immunotherapy or other investigational agents within 4 weeks before the first dose of BC006. Prior treatment with any anti-CSF-1R inhibitor. Any toxicity from previous anti-tumor treatments have not recovered to CTCAE V5.0 grade ≤ 1 (except treatment-related alopecia). Patients with untreated or clinically symptomatic brain metastases, spinal cord compression, cancerous meningitis, or patients with evidence that brain and spinal cord metastases have not been controlled (Patients with previously treated brain metastases may participate provided they are clinically and imaging stable for at least 4 weeks prior to first dose of BC006, have no evidence of cerebral edema and are off steroids). Patients with severe cardiovascular diseases: cardiac arrhythmia requiring clinical intervention; acute coronary syndrome, congestive heart failure, stroke or other ≥ grade 3 cardiovascular events within 6 months; New York Heart Association (NYHA) cardiac function ≥ grade II or left ventricular ejection fraction (LVEF) <50%; poorly controlled hypertension as judged by the investigator are not suitable to participate in the study. Receipt of a live vaccine within 4 weeks prior to the first dose of BC006 or anticipation that such a live vaccine will be required during the study. Patients with symptomatic pleural, abdominal, or pericardial effusions that require repeated puncture and drainage treatment and cannot be relieved; patients with stable disease after receiving treatment (including therapeutic thoracentesis or abdominal puncture) are allowed to enroll. In the opinion of the investigator, patients have any clinical or laboratory examination abnormality or other conditions that are not suitable to participate in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation: Phase Ia<br>Participants will receive escalating doses of BC006 at assigned dose (0.08, 0.3, 1.0, 3.0, 10, 20 mg/kg) via intravenous (IV) infusion every 2 weeks until disease progression, unacceptable toxicity, withdrawal of informed consent, or up to 48 weeks of treatment, whichever occurs first. | Drug: BC006<br>* BC006 monoclonal antibody injection<br>|
| Experimental: Dose Expansion: Phase Ib Cohort 1<br>Participants with GCTTS will receive BC006 at recommended dose for expansion (RDE) IV every 2 weeks until disease progression, unacceptable toxicity, withdrawal of informed consent, or up to 24 weeks of treatment, whichever occurs first. | Drug: BC006<br>* BC006 monoclonal antibody injection<br>|
| Experimental: Dose Expansion: Phase Ib Cohort 2 4<br>Participants with other solid tumors will receive BC006 at RDE IV every 2 weeks until disease progression, unacceptable toxicity, withdrawal of informed consent, or up to 48 weeks of treatment, whichever occurs first. | Drug: BC006<br>* BC006 monoclonal antibody injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Dose-limiting Toxicities (DLTs) | Dose Escalation: Phase Ia | Up to 28 days | 
| Maximum Tolerated Dose (MTD) of BC006 | Dose Escalation: Phase Ia | Up to 28 days | 
| Recommended Dose for Expansion (RDE) of BC006 | Dose Escalation: Phase Ia | Through study completion, an average of 1 year | 
| Number of Participants with TEAEs | Graded according to the NCI CTCAE V5.0 | Through study completion, an average of 1 year | 
| Number of Participants with SAEs | Graded according to the NCI CTCAE V5.0 | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Pharmacokinetic parameter, observed Maximum Serum Concentration (Cmax) of BC006 | From first dose of BC006, an average of 6 months | 
| Tmax | Pharmacokinetic parameter, Time-to-Maximum (Tmax) of BC006 | From first dose of BC006, an average of 6 months | 
| AUC0-t | Pharmacokinetic parameter, area under the plasma concentration time curve from time 0 to the time of last observed quantifiable concentration (AUC0-t) of BC006 | From first dose of BC006, an average of 6 months | 
| t1/2 | Pharmacokinetic parameters, apparent Terminal Half-life (t1/2) of BC006 | From first dose of BC006, an average of 6 months | 
| Pharmacodynamic (PD) Parameters | CSF-1 levels in peripheral blood | From first dose of BC006, an average of 6 months | 
| Number of Participants with Anti-BC006 Antibodies (ADAs) | ADA titer and Neutralizing Antibodies (NAbs) analysis will be performed when ADA is positive | From first dose of BC006, an average of 6 months | 
| 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 | From first dose of BC006, up to 2 years | 
| Disease Control Rate (DCR) | Disease control rate (DCR) is defined as the proportion of the optimal time response of CR, PR, disease stable (SD) (i.e. CR+PR+SD) between initiation of the trial drug and withdrawal from the trial, as assessed according to RECIST Version 1.1 | From first dose of BC006, up to 2 years | 
| Progression-Free Survival (PFS) | Progression-free survival (PFS) is defined as the time elapsed from the day the study drug was first administered until the first imaging assessment of disease progression (PD) or death from any cause. | From first dose of BC006, up to 2 years | 
| Duration of Response (DOR) | The duration of response (DOR) is defined as the time from the beginning of the first tumor assessment as PR or CR to the first assessment as PD or death from any cause. | From first dose of BC006, up to 2 years |