Study of TJ033721 (Givastomig) in Subjects With Advanced or Metastatic Solid Tumors

Official title

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

Overview

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

Interventions

• Drug TJ033721 (givastomig)
  Tetravalent IgG(H)-scFv fusion-type of bi-specific antibody (BsAb)
• Drug TJ033721 (givastomig) , nivolumab, chemotherapy
  Tetravalent IgG(H)-scFv fusion-type of bi-specific antibody (BsAb), nivolumab, chemotherapy
• Drug TJ033721 (givastomig), chemotherapy
  Tetravalent IgG(H)-scFv fusion-type of bi-specific antibody (BsAb), chemotherapy
• Drug TJ033721 (givastomig), durvalumab, chemotherapy
  Tetravalent IgG(H)-scFv fusion-type of bi-specific antibody (BsAb), durvalumab, chemotherapy

Primary outcome measures

• Dose-limiting toxicities (DLTs) [Time frame: 28 days]
• Incidence and severity of AEs [Time frame: Up to 100 days post last dose]
• Maximum tolerated or administered dose (MTD, MAD) [Time frame: 28 Days]

Secondary outcome measures (5)

• Pharmacokinetic (PK) Parameters: AUC∞ [Time frame: Up to 100 days post last dose]
• Pharmacokinetic (PK) Parameters: AUCt [Time frame: up to 100 days post last dose]
• Pharmacokinetic (PK) Parameters: Cmax [Time frame: up to 100 days post last dose]
• Pharmacokinetic Parameters: Tmax [Time frame: up to 100 days post last dose]
• Pharmacokinetic Parameters: T1/2 [Time frame: up to 100 days post last dose]

Eligibility 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;

Part 3: Combination Therapy Subjects with unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma;

Part 4: Combination Therapy Subjects with unresectable, locally advanced or metastatic histologically confirmed biliary tract cancer.

• 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, Part 3, Part 4 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, percutaneous transluminal coronary angioplasty (PTCA), 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

For Part 2, 3, 4 Combination subjects:

• Prior treatment with anti-PD-1 or PD-L1 agent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 11 centers

• Stern Center for Cancer Clinical Trials and Research — Orange
• UCHealth Cancer Care - Anschutz Medical Campus — Aurora
• Horizon Oncology Research, LLC. — Layfayette
• Mass General Hospital — Boston
• Rutgers Cancer Institute of New Jersey — New Brunswick
• NYU Langone — New York
• Memorial Sloan Kettering Cancer Center — New York
• Carolina BioOncology Institute — Huntersville
• … and 3 more centers

China · 10 centers

• The Second Hospital of Anhui Medical University — Hefei
• Beijing Cancer Hospital — Beijing
• Sixth Affiliated Hospital, Sun Yat-sen University — Guangzhou
• HARBIN Medical University Cancer Hospital — Harbin
• Henan Cancer Hospital — Zhengzhou
• Hubei Cancer Hospital — Wuhan
• The First Hospital of China Medical University — Shenyang
• Zhongshan Hospital, Fudan University — Shanghai
• … and 2 more centers

Identifiers

NCT: NCT04900818 · TJ033721STM101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗