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

Official title

A Phase 3, Randomized, Double-blind, Placebo-controlled Study Evaluating Combination of TST001, Pembrolizumab and Chemotherapy as First-Line Treatment in Subjects With Claudin18.2 Positive Locally Advanced or Metastatic Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma

Overview

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.

Detailed description

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.

Interventions

• Drug Pembrolizumab and either Capcecitabine + Oxaliplatin or Oxaliplatin+Leucovorin + 5-fluorouracil
  TST001 will be administered i.v. Q3W along with standard prescribing dose of pembrolizumab Q3W + standard prescribed regimens for FOLFOX6 or CapOx.
• Drug Pembrolizumab and either Capcecitabine + Oxaliplatin or Oxaliplatin+Leucovorin + 5-fluorouracil
  Placebo will be administered i.v. Q3W along with standard prescribing dose of pembrolizumab Q3W + standard prescribed regimens for FOLFOX6 or CapOx.

Primary outcome measures

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

Secondary outcome measures (6)

• Overall Survival (OS) based on RESIST [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) [Time frame: Date of randomization up to 24 months after last dose]
• Quality of Life (QOL) assessed on EuroQol EQ5D-5L [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 [Time frame: Date of randomization up to 24 months after last dose]
• Duration of Response (DOR) based on RESIST (log-rank test) [Time frame: From date of randomization up to 24 months after last dose]
• Time to Response (TTR) based on RESIST [Time frame: Date of randomization up to 24 months after last dose]

Eligibility criteria

Inclusion criteria

• 1\. ≥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.

3\. 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.

4\. Positive CLDN18.2 expression in tumor tissue confirmed by the central laboratory at screening using CTA (Claudin 18.2 IHC 14G11 pharmDx).

5\. 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.

6\. Subjects should be eligible to receive chemotherapy and pembrolizumab per the investigator judgement.

7\. Known PD-L1 CPS Status (tested by central laboratory to provide CPS status by PD-L1 IHC 22C3 pharmDx).

8\. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 14 days before randomization.

9\. 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.

10\. Have a life expectancy of greater than 12 weeks. 11. Demonstrate adequate organ function.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06093425 · TST001-3001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗