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

Description
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.

Objective
Primary Objectives:
to evaluate the safety and tolerability of TJ033721 in subjects with advanced or metastatic solid tumors;
to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of TJ033721;
to determine a recommended phase 2 dose (RP2D) of TJ033721.

Secondary Objectives:
to characterize the pharmacokinetic (PK) profile of TJ033721;
to evaluate pharmacodynamic (PD) profiling of TJ033721;
to evaluate the immunogenicity of TJ033721;
to assess preliminary antitumor activity of TJ033721 by assessing response rate by RECIST 1.1 and iRECIST.

Exploratory Objectives:
to explore associations of PD activity with efficacy and safety outcomes in subjects treated with TJ033721;
to explore the exposure-response relationship for PD activity in subjects treated with TJ033721;
to explore associations of exploratory biomarkers with PD activity in subjects treated with TJ033721.

Treatment Experimental: Dose Escalation: TJ033721
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
Tetravalent IgG(H)-scFv fusion-type of bi-specific antibody (BsAb)

Key Eligibility 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

Advanced or metastatic gastric cancer, gastroesophageal junction carcinoma, esophageal adenocarcinoma, and pancreatic ductal 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

Prior exposure to CLDN18.2 -targeted therapy

Prior exposure to 4-1BB agonists

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

Applicable Disease Sites
Anal; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Sarcoma; Uterus

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital