Study of TJ033721 in Subjects With Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This is an open label, multi-center, multiple dose Phase 1 study to evaluate the safety, tolerability, MTD PK, and PD of TJ033721 in subjects with advanced or metastatic solid tumors.

Official Title
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A Phase 1 Study of TJ033721 in Subjects With Advanced or Metastatic Solid Tumors

Conditions
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Solid Tumor, Advanced Cancer, Metastatic Cancer, Gastric Cancer, Gastroesophageal Junction Carcinoma, Esophageal Adenocarcinoma

Intervention / Treatment
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* Drug: TJ033721


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with advanced or metastatic solid tumor in subjects whose disease has progressed despite standard therapy, or who has no further standard therapy, or who is unsuitable for available standard treatment options. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with adequate organ function Have known PD-L1 status with prior testing by immunohistochemistry and a corresponding combined positive score (CPS) For dose expansion study only: Advanced or metastatic gastric cancer, gastroesophageal junction carcinoma, and esophageal adenocarcinoma without further standard therapy or unsuitable for available standard treatment options. Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay Exclusion Criteria Prior exposure to CLDN18.2 -targeted therapy Prior exposure to 4-1BB agonists Second malignancy within the last 3 years with the exception of cutaneous squamous cell carcinoma or cutaneous basal cell carcinoma or cervical carcinoma in situ Known active or chronic Hepatitis B or Hepatitis C, other hepatitides Unstable/active ulcer or digestive tract bleeding within 6 weeks Active autoimmune disease requiring systemic treatment within the past 2 years Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment Known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment; New York Heart Association (NYHA) Class 3 or 4 congestive heart failure, severe/unstable angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack (TIA), arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), deep vein thrombosis, or coronary artery bypass grafting (CABG) in the previous 6 months Diagnosis of immunodeficiency such as known active HIV Any active infection requiring parenteral treatment

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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation: TJ033721<br>Dose Escalation:: TJ033721 will be administered at up to 8 dose levels (0.1, 0.3, 1, 3, 5, 8, 12 and 15 mg/kg) bi-weekly (Q2W) During dose expansion, TJ033721 will be administered Q2W, starting at the highest dose to have cleared the DLT period. After the conclusion of dose expansion TJ033721 will be administered Q2W at the MAD or RP2D. | Drug: TJ033721<br>* Tetravalent IgG(H)-scFv fusion-type of bi-specific antibody (BsAb)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities (DLTs) |  | 28 days | 
| Incidence and severity of AEs | The CTCAE criteria will be used to assess adverse events on this trial. | Up to 100 days post last dose | 
| Maximum tolerated or administered dose (MTD, MAD) | Based on DLT definitions | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Parameters: AUC∞ | Area under the curve from time zero extrapolated to infinity (AUC∞) | Up to 100 days post last dose | 
| Pharmacokinetic (PK) Parameters: AUCt | AUC from time zero to the time of the last quantifiable concentration (AUC0-t) | up to 100 days post last dose | 
| Pharmacokinetic (PK) Parameters: Cmax | Maximum observed concentration | up to 100 days post last dose | 
| Pharmacokinetic Parameters: Tmax | Time of peak concentration (Tmax) | up to 100 days post last dose | 
| Pharmacokinetic Parameters: T1/2 | Investigational Product (IP) half-life (T1/2) | up to 100 days post last dose |