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.
This Phase 3, randomized, double-blind, placebo-controlled study is designed to evaluate the safety and efficacy of TST001 in combination with pembrolizumab 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
820
TST001 will be administered i.v. Q3W along with standard prescribing dose of pembrolizumab Q3W + standard prescribed regimens for FOLFOX6 or CapOx.
Placebo will be administered i.v. Q3W along with standard prescribing dose of pembrolizumab Q3W + standard prescribed regimens for FOLFOX6 or CapOx.
Progression free survival (PFS) based on RECIST (v1.1)
Compare PFS of patients treated with TST001 or Placebo in combination with pembrolizumab and chemotherapy
Time frame: 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.
Overall Survival (OS) based on RESIST
Compare OS of patients treated with TST001 or Placebo in addition to CapOx or mFOLFOX6 and pembrolizumab or CapOx or mFOLFOX6
Time frame: 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)
Compare OOR patients treated with TST001 or Placebo in addition to CapOx or mFOLFOX6 and pembrolizumab or CapOx or mFOLFOX6.
Time frame: Date of randomization up to 24 months after last dose
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 pembrolizumab or CapOx or mFOLFOX6. Assessments include Cancer QOL questionnaires (QLC-STO22, EQ5D-5L, and QLQ-C30)
Time frame: 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
Compare DCR of patients treated with TST001 or Placebo in addition to CapOx or mFOLFOX6 and pembrolizumab or CapOx or mFOLFOX6.
Time frame: Date of randomization up to 24 months after last dose
Duration of Response (DOR) based on RESIST (log-rank test)
Compare DOR of patients treated with TST001 or Placebo in addition to CapOx or mFOLFOX6 and pembrolizumab or CapOx or mFOLFOX6.
Time frame: From date of randomization up to 24 months after last dose
Time to Response (TTR) based on RESIST
Compare TTR of patients treated with TST001 or Placebo in addition to CapOx or mFOLFOX6 and pembrolizumab or CapOx or mFOLFOX6 based on CR or PR.
Time frame: Date of randomization up to 24 months after last dose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.