A Trial To Evaluate Safety And Tolerability Of TST001 In Advanced Or Metastatic Solid Tumors

Study Overview

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

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.

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.

Advanced Cancer
Gastric Cancer
Gastroesophageal-junction Cancer
Pancreatic Cancer

DRUG: TST001
DRUG: Nivolumab Injection [Opdivo]
DRUG: mFOLFOX6
DRUG: Gemcitabine
DRUG: Albumin-Bound Paclitaxel

TST001-1001

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2020-05-07	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-04-09
First Submitted that Met QC Criteria 2020-05-15	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-04-13
First Posted (ACTUAL) 2020-05-21	Results First Posted N/A	Last Verified 2024-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Part A Q2W Dosed every 2 weeks IV with TST001, starting dose is 1 mg/kg, multiple dose levels will be tested.	DRUG: TST001 TST001 is a humanized IgG1 monoclonal antibody.
EXPERIMENTAL: Part A Q3W Dosed every 3 weeks IV with TST001, starting dose is 3 mg/kg, and multiple dose levels will be tested.	DRUG: TST001 TST001 is a humanized IgG1 monoclonal antibody.
EXPERIMENTAL: Part B Cohort A Patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma.	DRUG: TST001 TST001 is a humanized IgG1 monoclonal antibody. DRUG: Nivolumab Injection [Opdivo] Nivolumab is one of the PD-1 checkpoint inhibitors, and has proved clinical benefit for multiple late-stage malignancies DRUG: mFOLFOX6 mFOLFOX6 is a combination chemotherapy regimen including the drugs leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin.
EXPERIMENTAL: Part B Cohort B Patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies.	DRUG: TST001 TST001 is a humanized IgG1 monoclonal antibody. DRUG: Nivolumab Injection [Opdivo] Nivolumab is one of the PD-1 checkpoint inhibitors, and has proved clinical benefit for multiple late-stage malignancies
EXPERIMENTAL: Part B Cohort C Patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma.	DRUG: TST001 TST001 is a humanized IgG1 monoclonal antibody. DRUG: Gemcitabine Chemotherapy medication DRUG: Albumin-Bound Paclitaxel Chemotherapy medication

Primary Outcome Measures	Measure Description	Time Frame
Participant Safety as characterized by frequency and severity of adverse events	Characterization of TST001 safety profile including frequency and severity of adverse events that are related to treatment.	up to 100 days following last dose
Maximum Tolerated Dose (MTD or Recommended Phase 2 Dose (RP2D)	As measured by number of participants experiencing dose related toxicity (DLT) in each escalating cohort	up to 100 days following last dose
Participant Safety and Tolerability of TST001 in combination with Nivolumab as characterized by frequency and severity of adverse events	Characterization of TST001 + Nivolumab safety profile including frequency and severity of adverse events that are related to treatment.	Up to 100 days following last dose
Participant Safety and Tolerability of TST001 in combination with Nivolumab and mFOLFOX6 as characterized by frequency and severity of adverse events	Characterization of TST001 + Nivolumab + mFOLFOX6 safety profile including frequency and severity of adverse events that are related to treatment.	Up to 100 days following last dose
Participant Safety and Tolerability of TST001 in combination with gemcitabine and albumin-bound paclitaxel as characterized by frequency and severity of adverse events	Characterization of TST001 + Gemcitabine + albumin-bound paclitaxel safety profile including frequency and severity of adverse events that are related to treatment.	Up to 100 days following last dose

Secondary Outcome Measures	Measure Description	Time Frame
Immunogenicity	by measurement of Incidence of anti-drug antibodies (ADA)	up to 30 days following last dose
Objective response rate (ORR)	as measured by RECIST 1.1	up to 24 months, until disease progression or start of another anti-cancer therapy
Duration of Response (DOR)	duration of response (DOR)	up to 24 months, until disease progression or start of another anti-cancer therapy
Progression free survival (PFS)	as measured by RECIST v1.1	up to 24 months, until disease progression or start of another anti-cancer therapy
PK parameters	Maximum serum concentration (Cmax)	Up to 30 days following last dose
PK	time to reach maximum serum concentration (Tmax)	Up to 30 days following last dose
PK	Area Under the Curve	Up to 30 days following last dose

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Bristol-Myers Squibb

Investigators

STUDY_DIRECTOR: Charlie Qi, MD, Suzhou Transcenta Therapeutics Co.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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