A Study of BA1202 in Patients With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, open-label, single-arm phase I study in patients with advanced solid tumors which consists of a dose escalation part (Part A) and a dose extension part (Part B). Part A aims to evaluate the safety and tolerability of BA1202, and determine the MTD. Part B will also evaluate the preliminary efficacy of BA1202.

Official Title
-----------------
A Multicenter, Open-label, Single-arm, Dose Escalation and Expansion Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of BA1202 in Patients With Advanced Solid Tumors

Conditions
-----------------
Advanced Solid Tumor

Intervention / Treatment
-----------------
* Drug: BA1202


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who voluntarily sign an IRB-approved informed consent form, and are willing to abide by the restrictions of the study. Part A: Patients with histologically and/or cytologically confirmed advanced and/or metastatic solid tumors who have progressed on Standard-Of-Care (SOC), are intolerant to SOC, or have no SOC. Part B: Patients with histologically and/or cytologically confirmed colorectal cancer, non-small cell lung cancer, pancreatic cancer, gastric cancer, who have progressed on Standard-Of-Care (SOC), are intolerant to SOC, or have no SOC.（Specific cohort will be determined after data of dose escalation phase is obtained） Part B: High expression of CEACAM5 (defined as ≥ 20% of tumor cells with IHC 2+ and/or 3+). Life expectancy of at least 3 months. At least one evaluable lesion in Part A and at least one measurable lesion in Part B according to RECIST v1.1. ECOG score of < 2. Absolute neutrophil count ≥ 1.5 x 10^9/L, platelet count ≥ 100 x 10^9/L, hemoglobin ≥ 90 g/L. Total bilirubin ≤ 1.5×ULN, ALT and AST ≤ 2.5×ULN (or ≤ 5.0×ULN for patients with liver metastases). Serum creatinine ≤ 1.5×ULN, or creatinine clearance ≥50 mL/min. International normalized ratio (INR) prothrombin time (PT) ≤1.5×ULN, activated partial thromboplastin time (APTT) ≤1.5×ULN. Blood pregnancy test results were negative for female patients with fertility potential. Patients with fertility potential must agree to use a reliable method of contraception with their sexual partners during the study period and at least 6 months after the last administration. Exclusion Criteria: Other malignancies within 5 years prior to screening (other than cured stage Ib or lower cervical cancer, non-invasive basal cell or squamous cell skin cancer). Has a persistent or active infection that requires intravenous treatment. History of severe cardiovascular and cerebrovascular disease. Patients with autoimmune diseases requiring drug control or at risk of recurrence of autoimmune diseases. Received any radiotherapy (other than palliative radiotherapy for bone metastases), chemotherapy, targeted therapy, immunotherapy, cell therapy, or other investigational anticancer agents within 4 weeks prior to first dose of BA1202, unless chemotherapy or targeted therapy is less than 4 weeks after first dose but has eluted ≥5 half-lives. Have received any previous CEA targeting therapy, including but not limited to monoclonal antibodies, bisspecific antibodies, antibody-coupled drugs (ADCs), chimeric antigen receptor T cells (CAR-T), etc. A history of allergy to BA1202 or any component of Obinutuzumab, or to other monoclonal antibodies. Women are planning to become pregnant or are pregnant or breastfeeding. Other conditions considered unsuitable for enrollment by the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BA1202<br>BA1202 is a bispecific antibody targeting CEA and CD3. | Drug: BA1202<br>* BA1202 will be administered intravenously (IV) once every 3 weeks (Q3W) until confirmed progression, death, unaccepted toxicity, initiation of other antitumor therapies, or any other conditions requiring treatment discontinuation, and the duration of administration was no more than 2 years. Part A: Patients will receive one of the following dosages of BA1202: 0.016mg, 0.08mg, 0.4mg, 1.6mg, 6.4mg, 19mg, 38mg, 56mg. Part B: Based on the data of part A, one or two dose levels will be discussed for further evaluation in part B.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AEs) |  | From the initiation of study treatment to the completion of safety follow-up after the end of study treatment, up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentration (Cmax) of BA1202 |  | Cycle 1: Day 1, 2, 3, 5, 8, 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 4: Day 1, 2, 3, 5, 8, 15; Cycle 5 Day 1; Cycle 6 Day 1. (Each cycle is 21 days.) | 
| Area under the curve (AUC) of BA1202 |  | Cycle 1: Day 1, 2, 3, 5, 8, 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 4: Day 1, 2, 3, 5, 8, 15; Cycle 5 Day 1; Cycle 6 Day 1. (Each cycle is 21 days.) | 
| Minimum Concentration (Cmin) of BA1202 |  | Cycle 1: Day 1, 2, 3, 5, 8, 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 4: Day 1, 2, 3, 5, 8, 15; Cycle 5 Day 1; Cycle 6 Day 1. (Each cycle is 21 days.) | 
| Time of maximum concentration (Tmax) of BA1202 |  | Cycle 1: Day 1, 2, 3, 5, 8, 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 4: Day 1, 2, 3, 5, 8, 15; Cycle 5 Day 1; Cycle 6 Day 1. (Each cycle is 21 days.) | 
| Objective Response Rate (ORR) |  | up to 2 years | 
| Disease Control Rate (DCR) |  | up to 2 years | 
| Duration of Response (DOR) |  | up to 2 years | 
| Overall Survival (OS) |  | up to 2 years | 
| Progression-Free Survival (PFS) |  | up to 2 years | 
| Proportion of subjects with positive anti-drug antibody (ADA) and neutralizing antibody (Nab) |  | Cycle 1: Day 1, 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1; EOT (end of treatment) visit. (Each cycle is 21 days.) |