A Trial to Evaluate Safety and Tolerability of TST001 in Advanced or Metastatic Solid Tumors

NCT ID: NCT04396821

Last Updated: 2025-12-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-28
• Study Completion Date: 2026-11-30

Brief Summary

This is an open label Phase I/IIa, First in Human trial of TST001, a recombinant humanized anti-Claudin 18.2 (CLDN18.2) IgG1 monoclonal antibody as monotherapy or in combination with nivolumab or standard of care. It is being tested against advanced and/or metastatic solid tumors including gastric, gastroesophageal junction, pancreatic cancers.

Detailed Description

Part A of the trial will consist of two cohorts, one dosed every 2 weeks and one dosed every 3 weeks in a standard 3+3 design. Part A is the dose finding portion of the trial.

18 to 36 participants will be enrolled.

Part B consists of 3 cohorts:

Cohort A is for patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma. Patients will receive TST001 at 2mg/kg or 4mg/kg Q2W plus Nivolumab and mFOLFOX6. Alternative allocation of patients between the 2 doses will be performed. The first 6 patients at each dose level as the lead-in phase will not be selected on the basis of their tumor's CLDN18.2 expression. Approximately 12-42 patients will be enrolled in Cohort A.

Cohort B is for patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies. Patient will receive TST001 plus Nivolumab. No selection based on CLDN18.2 expression will be required for the safety run-in (3-6 patients). Patients with CLDN18.2 expression in tumor tissue tested by the central laboratory will be enrolled in the expansion phase. Safety run-in phase will follow 3+3 rule with two dose levels, TST001 3mg/kg and 6mg/kg Q3W combined with nivolumab. Approximately 30 patients will be enrolled in Cohort B including the patients in the safety run-in phase.

Cohort C is for patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma; Patients will receive TST001 at 2mg/kg or 4mg/kg Q2W plus gemcitabine and albumin-bound paclitaxel. Alternative allocation of patients between the 2 doses will be performed. The first 6 patients at each dose level as the lead-in phase will not be selected on the basis of their tumor's CLDN18.2 expression. Approximately 12-42 patients will be enrolled in Cohort C.

Conditions

Advanced Cancer; Gastric Cancer; Gastroesophageal-junction Cancer; Pancreatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A Q2W

Dosed every 2 weeks IV with TST001, starting dose is 1 mg/kg, multiple dose levels will be tested.

Group Type: EXPERIMENTAL

TST001

Intervention Type: DRUG

TST001 is a humanized IgG1 monoclonal antibody.

Part A Q3W

Dosed every 3 weeks IV with TST001, starting dose is 3 mg/kg, and multiple dose levels will be tested.

Group Type: EXPERIMENTAL

TST001

Intervention Type: DRUG

TST001 is a humanized IgG1 monoclonal antibody.

Part B Cohort A

Patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma.

Group Type: EXPERIMENTAL

TST001

Intervention Type: DRUG

TST001 is a humanized IgG1 monoclonal antibody.

Nivolumab Injection [Opdivo]

Intervention Type: DRUG

Nivolumab is one of the PD-1 checkpoint inhibitors, and has proved clinical benefit for multiple late-stage malignancies

mFOLFOX6

Intervention Type: DRUG

mFOLFOX6 is a combination chemotherapy regimen including the drugs leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin.

Part B Cohort B

Patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies.

Group Type: EXPERIMENTAL

TST001

Intervention Type: DRUG

TST001 is a humanized IgG1 monoclonal antibody.

Nivolumab Injection [Opdivo]

Intervention Type: DRUG

Nivolumab is one of the PD-1 checkpoint inhibitors, and has proved clinical benefit for multiple late-stage malignancies

Part B Cohort C

Patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma.

Group Type: EXPERIMENTAL

TST001

Intervention Type: DRUG

TST001 is a humanized IgG1 monoclonal antibody.

Gemcitabine

Intervention Type: DRUG

Chemotherapy medication

Albumin-Bound Paclitaxel

Intervention Type: DRUG

Chemotherapy medication

Interventions

TST001

TST001 is a humanized IgG1 monoclonal antibody.

Intervention Type: DRUG

Nivolumab Injection [Opdivo]

Nivolumab is one of the PD-1 checkpoint inhibitors, and has proved clinical benefit for multiple late-stage malignancies

Intervention Type: DRUG

mFOLFOX6

mFOLFOX6 is a combination chemotherapy regimen including the drugs leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin.

Intervention Type: DRUG

Gemcitabine

Chemotherapy medication

Intervention Type: DRUG

Albumin-Bound Paclitaxel

Chemotherapy medication

Intervention Type: DRUG

Other Intervention Names

Gemzar

Eligibility Criteria

Inclusion Criteria

• Male or female ≥ 18 years.
• Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors.

Part A only:

• Patients must be: a) progressed after standard therapies, b) intolerant of standard therapies, or c) with a tumor type without standard therapy.

Part B only:

• Cohort A: Patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma; prior adjuvant or neoadjuvant therapy are allowed only if disease progressed or recurred at least 6 months after completion of these treatments. Patients may have received one infusion of mFOLFOX6 plus nivolumab during the screening period.
• Cohort B: Patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies; adjuvant or neoadjuvant therapy could be regarded as one line of therapy only if disease progressed or recurred during these treatments or within 6 months or less after completion of these treatments.
• Cohort C: Patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma; prior adjuvant or neoadjuvant therapy are allowed only if disease progressed or recurred at least 6 months after completion of these treatments. Patients may have received up to 2 infusions of Gemcitabine + albumin-bound paclitaxel (with one week between each infusion) during the screening period.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0-1 .
• Patients with adequate cardiac, liver, renal function, etc.

Exclusion Criteria

• Symptomatic central nervous system metastases.
• Prior treatment with any CLDN18.2 target agents
• Allergy or sensitivity to TST001 or known allergies to comparable drugs
• Documented history of multiple other allergies requiring interventions
• Severe cardiovascular disease, including CVA, TIA, myocardial infarction, or unstable angina, NYHA class III or IV heart failure or uncontrolled arrhythmia within 6 months of study entry, severe QTc prolongation, concomitant risks for QTc prolongation.
• Concurrent malignancy within 5 years prior to entry except adequately treated certain types of cancer
• Active and clinically significant infections, known uncontrolled infections with hepatitis B, hepatitis C, known human immunodeficiency virus with acquired immunodeficiency syndrome related illness
• Any condition that the investigator or primary physician believes may not be appropriate for participating in the study.

.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Suzhou Transcenta Therapeutics Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charlie Qi, MD

Role: STUDY_DIRECTOR

Suzhou Transcenta Therapeutics Co.

Locations

Banner MD Anderson

Gilbert, Arizona, United States

University of Arizona

Tucson, Arizona, United States

Yale University

New Haven, Connecticut, United States

Florida Cancer Specialists

Sarasota, Florida, United States

Emory University

Atlanta, Georgia, United States

University of Kansas, School of Medicine

Kansas City, Kansas, United States

Washington University

St Louis, Missouri, United States

Memorial Sloan Kettering

New York, New York, United States

Stony Brook Cancer Center

Stony Brook, New York, United States

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Gabrail Cancer Research

Canton, Ohio, United States

Pennsylvania Cancer Specialist Research Institute

Gettysburg, Pennsylvania, United States

Allegheny Hospital

Pittsburgh, Pennsylvania, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Vanderbilt University

Nashville, Tennessee, United States

NEXT Oncology

Austin, Texas, United States

Swedish Cancer Institute

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

TST001-1001

Identifier Type: -

Identifier Source: org_study_id