Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06093425
Other study ID # TST001-3001
Secondary ID
Status Not yet recruiting
Phase Phase 3
First received
Last updated
Start date October 31, 2023
Est. completion date January 31, 2026

Study information

Verified date October 2023
Source Suzhou Transcenta Therapeutics Co., Ltd.
Contact C Qi, MD
Phone +86 57128279502
Email charlie.qi@transcenta.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Gastric/GEJ adenocarcinomas are aggressive tumors with a high probability of death. Current treatment guidelines include two-drug cytotoxic chemotherapy with a fluoropyrimidine (mFOLFOX6: capecitabine or fluorouracil) and a platinum-based agent (CapOx: oxaliplatin or cisplatin). In addition, the FDA has recently approved nivolumab, a PD-1 checkpoint inhibitor, in combination with chemotherapy as first line treatment for advanced or metastatic gastric/GEJ cancer. TST001 is a recombinant humanized monoclonal antibody against Claudin (a tumor marker found in gastric/GEJ cancer. In this study, the combination therapy of chemotherapy or chemotherapy and nivolumab with and without TST001 (a novel recombinant humanized antibody) could provide additional benefits to the management of these tumors.


Description:

This Phase 3, randomized, double-blind, placebo-controlled study is designed to evaluate the safety and efficacy of TST001 in combination with nivolumab and chemotherapy or chemotherapy alone in subjects with tumors that express markers (HER2 negative, Claudin18.2 positive, known PD-L1 CPS status) in locally advanced or metastatic gastric/GEJ adenocarcinoma. Patients will be randomized in a 1:1 ration to receive TST001 or placebo in combination with nivolumab and chemotherapy or with chemotherapy alone.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 950
Est. completion date January 31, 2026
Est. primary completion date October 1, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of previously untreated, unresectable locally advanced or metastatic gastric/GEJ adenocarcinoma. - Must be willing and able to provide archival or fresh tissue sample, a formalin-fixed, paraffin-embedded (FFPE) block, or 10 or more unstained, freshly cut, serial sections (on slides) from an FFPE tumor specimen from a tumor lesion (either primary or metastatic) not previously irradiated or fresh biopsy tissue fixed in formalin solution. FFPE tissue blocks are preferred to slides. - Biomarkers positive CDLN18.2 expression and PD-L1 CPS Status - Must have at least one measurable lesion or evaluable disease - Subjects should be eligible to receive chemotherapy per local guidelines Exclusion Criteria: - Any prior systemic anticancer treatment (chemotherapy, immunotherapy, biologic therapy, or targeted therapy) for gastric/GEJ adenocarcinoma. - Has received prior radiotherapy within 2 weeks before randomization - Anti-CLDN18.2 agents at any time. - Any traditional Chinese medicine or proprietary Chinese medicine with anti-tumor effect within 7 days before randomization. - Any vaccines (live, attenuated, or research vaccines) within 30 days of dosing. - Gastrointestinal abnormalities including: Documented unresolved gastric outlet obstruction or persistent vomiting defined as =3 episodes within 24 hours within 2 weeks before randomization. Uncontrolled peptic ulcer disease Clinically significant gastrointestinal bleeding as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy - Squamous cell or undifferentiated gastric cancer - HER2 positive tumor defined as immunohistochemistry 3+ or ISH/FISH positive - Known additional malignancy that is progressing or has required active treatment within the past 5 years. - Known symptomatic or progressive CNS metastases and/or carcinomatous meningitis. - Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior randomization. - Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of immunomodulatory agents, corticosteroids or immunosuppressive drugs). - Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease. - Has Grade = 2 peripheral sensory neuropathy - Has an active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 2 weeks of Cycle 1 Day 1 (first dose of study treatment). - Has a known history of HIV infection. Subjects with a CD4+ T cell count > 350 cells/µL and no history of an AIDS-defining opportunistic infections are eligible for entry. HIV testing is required only for the subject's safety at the discretion of the investigator. - Has active viral hepatitis. Subjects with serologic evidence of HBV infection (defined by a positive hepatitis B surface antigen test) who have a viral load below the limit quantification (HBV DNA titer < 1000 cps/mL or 200 IU/mL) and are not currently on viral suppressive therapy may be eligible. Subjects with a history of HCV infection should have completed curative antiviral treatment and have a viral load below the limit of quantification. - Major surgery within 4 weeks prior to study entry; Minor surgery within 2 weeks prior to study entry. Has not recovered from the procedure and/or any complications from the surgery prior to randomization. - Severe cardiovascular disease, including cerebral vascular accident, transient ischemic attack, myocardial infarction, or unstable angina, NYHA class III or IV heart failure or = Grade 2 uncontrolled arrhythmia within 6 months of screening. - Corrected QTcF =470 ms (male) and =480 ms (female) at baseline (Fridericia); taking concomitant medications that would prolong the QT interval; or with family history of long QT syndrome - Prior stem cell, bone marrow or solid organ transplant. - Has a history or current evidence of any condition (including psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Study Design


Intervention

Drug:
TST001, CapOx or mFOLFOX6 and NIVO or (Substudy) TST001, Oxaliplatin and capecitabine or 5-fluorouracil (5-FU)
All medications administered intravenously
Placebo CapOx or mFOLFOX6 and NIVO or (Substudy) Placebo, Oxaliplatin and capecitabine or 5-fluorouracil (5-FU)
All medications administered intravenously

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Suzhou Transcenta Therapeutics Co., Ltd.

Outcome

Type Measure Description Time frame Safety issue
Primary Progression free survival (PFS) based on RECIST (1.1) Compare PFS of patients treated with TST001 or Placebo in addition to CapOx or mFOLFOX6 and nivolumab or CapOx or mFOLFOX6 From date of randomization until the date of documented progression, assessed up to 100 days after last dose
Secondary Overall Survival (OS) based on RESIST (log-rank test) Compare OS of patients treated with TST001 or Placebo in addition to CapOx or mFOLFOX6 and nivolumab or CapOx or mFOLFOX6 rom date of randomization until the date of documented progression, assessed up to 100 days after last dose
Secondary Overall Response Rate (ORR) based on RESIST progressive disease (log-rank test) Compare complete response (CR) or partial response (PR) between treatment arms of patients treated with TST001 or Placebo in addition to CapOx or mFOLFOX6 and nivolumab or CapOx or mFOLFOX6. From date of randomization until the date of documented CR or PR assessed up to 100 days after last dose
Secondary Quality of Life (QOL) assessed on EuroQol EQ5D-5L Change in QOL assessments from baseline of patients treated with TST001 or Placebo in addition to mFOLFOX6 and nivolumab or CapOx or mFOLFOX6. Assessments include Cancer QOL questionnaires (QLC-STO22, EQ5D-5L, and QLQ-C30) From date of randomization until the date of documented progression, assessed up to 100 days after last dose
Secondary Disease Control Rate (DCR) based on RESIST assessed as the percentage of subjects with measurable disease Compare complete response (CR), partial response (PR), or stable disease (SD) between treatment arms of patients treated with TST001 or Placebo in addition to CapOx or mFOLFOX6 and nivolumab or CapOx or mFOLFOX6. From date of randomization until the date of documented progression, assessed up to 100 days after last dose
Secondary Duration of Response (DOR) based on RESIST (log-rank test) Compare duration of response between treatment arms of patients treated with TST001 or Placebo in addition to CapOx or mFOLFOX6 and nivolumab or CapOx or mFOLFOX6. From date of randomization until the date of documented progression, assessed up to 100 days after last dose
Secondary Time to Response (TTR) of progression based on RESIST Compare the time of response between treatment arms of patients treated with TST001 or Placebo in addition to CapOx or mFOLFOX6 and nivolumab or CapOx or mFOLFOX6 based on CR or PR. From date of randomization until the date of documented progression, assessed up to 100 days after last dose
See also
  Status Clinical Trial Phase
Recruiting NCT05551416 - The EpiGASTRIC/EDGAR Project: New Strategies for the Early Detection and Prevention of Gastric Cancer
Completed NCT05518929 - Hypoxia During Gastroenterological Endoscope Procedures Sedated With Ciprofol In Overweight Or Obesity Patients Phase 4
Recruiting NCT06006390 - CEA Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of CEA Positive Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT03219593 - Apatinib as the First-Line Therapy in Elderly Locally Advanced or Metastatic Gastric Cancer Phase 2
Recruiting NCT05489211 - Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03) Phase 2
Recruiting NCT05536102 - The Effectiveness and Safety of XELOX and Tislelizumab + PLD for Resectable Gastric Cancer (LidingStudy) Phase 2
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Recruiting NCT06010862 - Clinical Study of CEA-targeted CAR-T Therapy for CEA-positive Advanced/Metastatic Malignant Solid Tumors Phase 1
Recruiting NCT05415098 - Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas Phase 1
Active, not recruiting NCT04082364 - Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer Phase 2/Phase 3
Withdrawn NCT03766607 - Trastuzumab Beyond Progression in HER2 Positive Metastatic Gastric Cancer Phase 2
Recruiting NCT04118114 - Phase II Study of PRL3-ZUMAB in Advanced Solid Tumors Phase 2
Completed NCT01924533 - Efficacy and Safety Study of Olaparib in Combination With Paclitaxel to Treat Advanced Gastric Cancer. Phase 3
Terminated NCT01641939 - A Study of Trastuzumab Emtansine Versus Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer Phase 2/Phase 3
Recruiting NCT05107674 - A Study of NX-1607 in Adults With Advanced Malignancies Phase 1
Active, not recruiting NCT04908813 - Study of HLX22 in Combanition With Trastuzumab and Chemotherapy Versus Placebo in Combination With Trastuzumab and Chemotherapy for Treatment of Locally Advanced or Metastatic Gastric Cancer Phase 2
Active, not recruiting NCT04249739 - Pembrolizumab + Capecitabine/Oxaliplatin (CapeOx) -HER2 Nagative and Pembrolizumab + Trastuzumab + Cisplatin/Capecitabine HER2 Positive Phase 2
Recruiting NCT05514158 - To Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Disitamab Vedotin Combined With RC98 in the Treatment of Subjects With HER2-expressing Locally Advanced or Metastatic Gastric Cancer (Including AEG) Phase 1
Recruiting NCT04931654 - A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer Phase 1/Phase 2
Recruiting NCT03175224 - APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors Phase 2