A First-in-Human, Phase 1 Study of TST003 in Subjects With Solid Tumors

NCT05731271 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: TST003-1001
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial is to test the safety of TST003 in patients with cancer. The main question\[s\] it aims to answer are:

• What is the recommended dose patients can safely receive?
• How long does this drug remain in the body after administration?
• What are the side effects of this drug?
• Does your cancer respond to TST003?
• Participants on this study will get TST003 intravenously (through a needle into your vein), once every 3 weeks.
• You may need to come to the study site 2-4 times to have tests to see if you are eligible to be in the study before you begin to receive the study drug.
• After you start the study drug, you will need to return to the site several times after each dose so the physician can take vital signs, draw blood samples, and evaluate you for safety and wellbeing.
• Participants will continue taking the drug as long as they are receiving clinical benefit.
• At the end of your study participation, additional testing is required.

Conditions

Locally Advanced Solid Tumor; Metastatic Tumor; Colorectal Adenocarcinoma

Outcome Measures

Primary Outcomes (9)

• Assess the Dose limiting toxicities of TST003

  Assess the Dose limiting toxicities experienced

  Observed during the first 21 day cycle

• Assess Adverse events (AEs) of TST003

  Assess Adverse events (AEs) as characterized by nature, frequency, and severity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

  through study completion, an average of 1 year

• Assess abnormal findings related to TST003

  Assess the abnormal findings of vital sign, physical examination, laboratory measurements, electrocardiogram (ECG) and echocardiogram (ECHO)/ multigated acquisition scan (MUGA) parameters

  through study completion, an average of 1 year

• assess the Overall Response Rate of TST003 as monotherapy at the RP2D in subjects with locally advanced or metastatic GREM1 positive solid tumors (Phase 1bPart)

  Overall Response Rate

  through study completion, an average of 1 year

• assess the Duration of Response of TST003 as monotherapy at the RP2D in subjects with locally advanced or metastatic GREM1 positive solid tumors (Phase 1bPart)

  Duration of Response

  through study completion, an average of 1 year

• assess the Time to Response of TST003 as monotherapy at the RP2D in subjects with locally advanced or metastatic GREM1 positive solid tumors (Phase 1bPart)

  Time to Response

  through study completion, an average of 1 year

• assess the Disease Control Rate of TST003 as monotherapy at the RP2D in subjects with locally advanced or metastatic GREM1 positive solid tumors (Phase 1bPart)

  Disease Control Rate

  through study completion, an average of 1 year

• assess the Progression Free Survival of TST003 as monotherapy at the RP2D in subjects with locally advanced or metastatic GREM1 positive solid tumors (Phase 1bPart)

  Progression Free Survival

  through study completion, an average of 1 year

• assess the Overall Survival of TST003 as monotherapy at the RP2D in subjects with locally advanced or metastatic GREM1 positive solid tumors (Phase 1bPart)

  Overall Survival Based on investigators' assessment using RECISTv1.1

  through study completion, an average of 1 year

Secondary Outcomes (5)

• To characterize Area under the Curve (AUC) of TST003

  through study completion, an average of 1 year

• To characterize Cmax of TST003

  Measured while the patient is on study

• To Determine Trough serum concentration of TST003

  through study completion, an average of 1 year

• Determine the formation of Anti-drug antibody (ADA) against TST003

  through study completion, an average of 1 year

• Determine the formation of Neutralizing antibodies (NAb) against TST003

  through study completion, an average of 1 year

Other Outcomes (2)

• To assess biomarkers in tumor tissue , and the correlation between biomarkers and PK, pharmacodynamic and clinical outcomes of TST003

  through study completion, an average of 1 year

• To assess biomarkers, in blood and the correlation between biomarkers and PK, pharmacodynamic and clinical outcomes of TST003

  through study completion, an average of 1 year

Study Arms (2)

Phase 1a Part - TST003 Dose Escalation

EXPERIMENTAL

TST003 administered every 3 weeks at increasing doses 1 mg/kg, 3 mg/kg, 10 mg/kg, 20 mg/kg, 30 mg/kg

Drug: TST003

Phase 1b Part - Dose Expansion at Recommended Phase 2 dose

EXPERIMENTAL

Administer TST003 every 3 weeks to patients with positive GREM1 tumor expression at the recommended Phase 2 Dose,

Drug: TST003

Interventions

TST003 DRUG

IV humanized anti-GREM1 monoclonal antibody

Phase 1a Part - TST003 Dose Escalation; Phase 1b Part - Dose Expansion at Recommended Phase 2 dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age at the time of informed consent.
• Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
• Part 1: Subjects with histological or cytological diagnosed unresectable locally advanced or metastatic malignant solid tumors and who can provide archival tumor tissue. For Part 2: Subjects with histological or cytological diagnosed unresectable locally advanced or metastatic CRC and who can provide archival tumor tissue
• Subjects who have tumor progression during or after prior therapy and for whom no standard therapy exists that would confer clinical benefit.
• At least 1 measurable lesion per RECIST v1.1 ( Part 2 only).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Life expectancy of 12 weeks or more.
• Calculated creatinine clearance ≥30 mL/min per the Cockcroft and Gault formula. 9.Adequate bone marrow function:
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 ×103/L);
• Platelets ≥ 100,000/mm3 (≥ 100 × 109/L);
• Hemoglobin ≥ 9.0 g/dL;
• Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) ≤ 1.5 and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 ULN (unless subjects are receiving therapeutic anti-coagulation which affects these parameters, and patients receiving therapeutic anticoagulation should be on a stable dose).
• Adequate liver function as evidenced by bilirubin ≤1.5 × ULN and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN.
• Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception during the treatment period and for at least 90 days after the last dose of TST003. Contraception methods should be consistent with local regulations.

You may not qualify if:

• Untreated or symptomatic central nervous system (CNS) metastases. Note: Subjects with asymptomatic treated CNS metastases are eligible provided they have been clinically stable and not requiring steroid for at least 4 weeks following CNS -directed therapy are eligible for study entry.
• Prior systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, or targeted therapy or herbal medicine) within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose of study drug.
• Radical radiation or local-regional therapies (transarterial chemoembolization or radiofrequency ablation) within 4 weeks prior to the first dose of study drug; palliative radiotherapy to a non-target lesion within 2 weeks prior to of study drug.
• Any unresolved Grade 2 or greater toxicity from previous anticancer therapy except alopecia.
• Any herbal medicine without anti-tumor intent within one week before the first dose of study drug.
• History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases, including but not limited to pulmonary fibrosis, active pneumonitis.
• Severe cardiovascular disease, including cerebrovascular accident, transient ischemic attack, myocardial infarction, or unstable angina, New York Heart Association (NYHA) class III or IV heart failure or uncontrolled arrhythmia within 6 months of the first dose.
• Has the average corrected QT interval by Fridericia's formula (QTcF) prolongation to \> 480 millisecond (ms) based on 12-lead ECG in triplicate, or with a history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives).
• Uncontrolled hypertension (systolic pressure \>150mmHg or diastolic pressure \> 90mmHg).
• Severe intestinal disease, including but not limited to:
• Peptic ulcer disease in the past 3 months prior to the first dosing.
• Clinically significant gastrointestinal bleeding as evidenced by hematemesis, hematochezia, or melena in the past 3 months prior to the first dosing without evidence of resolution documented by endoscopy or colonoscopy.
• Active colitis requiring ongoing treatment within 4 weeks prior to the first dosing, including infectious colitis, radiation colitis and ischemic colitis.
• History of ulcerative colitis or Crohn's disease.
• Active or uncontrolled infections requiring IV of antibiotics, antivirals, or antifungals.

Sponsors & Collaborators

• Suzhou Transcenta Therapeutics Co., Ltd.: lead

Study Sites (3)

OHSU

Portland, Oregon, 97239, United States

Location

Mary Crowley

Dallas, Texas, 75231, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Interventional Model: Sequential Assignment Interventional Model Description: Bayesian Optimal Interval (BOIN) design followed by evaluation for efficacy and safety of TST003 as monotherapy at the recommended dose for dose expansion phase or RP2D in subjects with locally advanced or metastatic colorectal cancer (CRCMasking: None (Open Label)

Study Record Dates

• First Submitted: January 5, 2023
• First Posted: February 16, 2023
• Study Start: February 8, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

US (3)