Combination of Osemitamab (TST001), Pembrolizumab and Chemotherapy as First-line Therapy in Advanced or Metastatic GC/GEJ Adenocarcinoma

NCT06093425 | Not Yet Recruiting Phase 3 FDA Drug

• 1 other identifier: TST001-3001
• Study Type: interventional
• Target: 820
• Locations: 0 countries
• Sites: N/A

Brief 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 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 18.2 (a tumor marker found in gastric/GEJ cancer. In this study, the combination therapy of chemotherapy or chemotherapy and pembrolizumab with and without TST001 could provide additional benefits to the management of these tumors.

Conditions

Gastroesophageal-junction Cancer; Advanced Cancer; Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) based on RECIST (v1.1)

  Compare PFS of patients treated with TST001 or Placebo in combination with pembrolizumab and chemotherapy

  Date of randomization until the date of documented progression or date of death due to any cause, whichever comes first up to 24 months after last dose.

Secondary Outcomes (6)

• Overall Survival (OS) based on RESIST

  Time from date of randomization until the date of death due to any cause, assessed up to 24 months after last dose.

• Overall Response Rate (ORR) based on RESIST (v1.1)

  Date of randomization up to 24 months after last dose

• Quality of Life (QOL) assessed on EuroQol EQ5D-5L

  Date of randomization until the date of documented progression, assessed up to 24 months after last dose

• Disease Control Rate (DCR) based on RESIST assessed as the percentage of subjects with measurable disease

  Date of randomization up to 24 months after last dose

• Duration of Response (DOR) based on RESIST (log-rank test)

  From date of randomization up to 24 months after last dose

Study Arms (2)

TST001 + PDL-1 + Chemotherapy

ACTIVE COMPARATOR

TST001 + Pembrolizumab + Chemotherapy (FOLFOX6 or CapOx)

Drug: Pembrolizumab and either Capcecitabine + Oxaliplatin or Oxaliplatin+Leucovorin + 5-fluorouracil

Placebo

PLACEBO COMPARATOR

Placebo + Pembrolizumab + Chemotherapy (FOLFOX6 or CapOx)

Drug: Pembrolizumab and either Capcecitabine + Oxaliplatin or Oxaliplatin+Leucovorin + 5-fluorouracil

Interventions

Pembrolizumab and either Capcecitabine + Oxaliplatin or Oxaliplatin+Leucovorin + 5-fluorouracil DRUG

TST001 will be administered i.v. Q3W along with standard prescribing dose of pembrolizumab Q3W + standard prescribed regimens for FOLFOX6 or CapOx.

Placebo

Eligibility Criteria

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

You may qualify if:

• \. ≥18 years of age on day of signing informed consent. 2. Histologically or cytologically confirmed diagnosis of previously untreated, unresectable locally advanced or metastatic G/GEJ adenocarcinoma.
• \. Must be willing and able to provide archival or fresh tissue sample, a formalin-fixed, paraffin-embedded (FFPE) block, or 151 or more unstained, freshly cut, serial sections (on slides) from an FFPE tumor specimen or fresh biopsy tissue from a tumor lesion (either primary or metastatic) not previously irradiated fixed in formalin solution. FFPE tissue blocks are preferred to slides. Notes: details pertaining to tumor tissue submission can be found in the Laboratory Manual. Fresh biopsies are not required for study entry and will not be covered as part of the study procedures. Handling of the fresh biopsy tissue is an alternative offered to investigators in case they plan to biopsy the subjects as part of their standard of care; the fresh sample can be sent directly to the central laboratory if it is more convenient to the sites.
• \. Positive CLDN18.2 expression in tumor tissue confirmed by the central laboratory at screening using CTA (Claudin 18.2 IHC 14G11 pharmDx).
• \. Must have at least one measurable lesion or evaluable disease by CT or MRI per RECIST 1.1 criteria as assessed locally by the investigator; radiographic tumor assessment should be performed within 28 days prior to randomization.
• \. Subjects should be eligible to receive chemotherapy and pembrolizumab per the investigator judgement.
• \. Known PD-L1 CPS Status (tested by central laboratory to provide CPS status by PD-L1 IHC 22C3 pharmDx).
• \. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 14 days before randomization.
• \. Subjects who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or pre-treatment status. Subjects with endocrine-related AEs who are adequately treated with hormone replacement or subjects who have ≤Grade 2 neuropathy are eligible.
• \. Have a life expectancy of greater than 12 weeks. 11. Demonstrate adequate organ function.

You may not qualify if:

• Has received any prior systemic anticancer treatment (chemotherapy, immunotherapy, biologic therapy, or targeted therapy) for G/GEJ adenocarcinoma. Neo/adjuvant treatment is permitted as long as it was completed at least 6 months prior to randomization.
• Has received prior radiotherapy within 2 weeks before randomization; Note: Subjects must have recovered from all radiation-related toxicities. A previously irradiated lesion can be used as measurable lesion as long as it progressed post radiation therapy.
• Has received anti-CLDN18.2 agents at any time.
• Has received any traditional Chinese medicine or proprietary Chinese medicine with anti-tumor effect within 7 days before randomization.
• Has received vaccines (live, attenuated, or research vaccines) within 30 days before randomization. Administration of killed vaccines is allowed.

Sponsors & Collaborators

• Suzhou Transcenta Therapeutics Co., Ltd.: lead

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

pembrolizumab; Oxaliplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

C Qi, MD

CONTACT

+86 57128279502; charlie.qi@transcenta.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Placebo-Controlled

Study Record Dates

• First Submitted: September 24, 2023
• First Posted: October 23, 2023
• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): January 31, 2030
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share