Study of TJ033721 in Subjects With Advanced or Metastatic Solid Tumors

I-Mab Biopharma

Status and phase: Enrolling; Phase 1

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

Treatments: Drug: TJ033721, nivolumab, chemotherapy; Drug: TJ033721

Study type: Interventional

Funder types: Industry

Identifiers

NCT04900818

TJ033721STM101

Details and patient eligibility

About

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.

Enrollment: 168 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Part 1 - Monotherapy • 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.

Part 2 - Combination Therapy Subjects with treatment naïve locally advanced, unresectable or metastatic gastric, GEJ, esophageal adenocarcinoma;

• 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 and Part 2 Combination subjects:

• Must have CLDN18.2-positive tumor expression

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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168 participants in 2 patient groups

TJ033721

Experimental group

Description:

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) and 1 dose level (18 mg/kg) every 3 weeks (Q3W) During dose expansion, TJ033721 will be administered Q2W, starting at the RP2D or MTD in dose escalation.

Treatment:

Drug: TJ033721

TJ033721 in combination with nivolumab and chemotherapy

Experimental group

Description:

TJ033721 will be administered in combination with nivolumab and chemotherapy

Treatment:

Drug: TJ033721, nivolumab, chemotherapy