Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes

Summary

Abstract Study title: Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes Protocol No: GC-MATCH Initiator: Henan Cancer Hospital Nature of study Investigator-initiated exploratory study Subjects Advanced first-line gastric cancer or adenocarcinoma of the gastroesophageal junction Objective: To evaluate the efficacy and safety of different first-line treatment options for unresectable locally advanced/advanced gastric or combined gastroesophageal adenocarcinoma with different gene/protein types.

Evaluation criteria: To evaluate the adverse effects of drugs using the NCI CTCAE V5.0 criteria.

RECIST1.1 criteria were used to evaluate drug efficacy Study endpoints: Primary indicators Objective Response Rate (ORR) Secondary indicators 1. drug safety. 2. disease control rate DCR (CR+PR+SD). 3. duration of remission DoR. 4. disease-free survival (PFS) and overall survival time (OS). 5. R0/R1 surgical resection rate Study design: Single-center umbrella clinical trial Planned number of enrollment: Total 39-45 cases Sample size estimation: This is an exploratory study and sample size was not calculated Statistical methods: Selection of data for statistical analysis Full Analysis Set (FAS): The efficacy analysis was performed on all patients who were enrolled and used the drug at least once, according to the principle of intentional analysis (ITT).

Per-protocol Set: Cases with at least one oncologic efficacy assessment, compliance with the trial protocol, good compliance, no prohibited drugs during the trial, and completion of the case report form.

Safety Analysis Set: All patients who had used the trial drug at least once and had a safety record after the drug was administered were enrolled in the Safety Analysis Set.

Statistical analysis plan Validity analysis: for the efficacy index PFS, the Kaplan-Meier method will be used to estimate its median time and column Statistical methods: Out of two-sided 95% confidence intervals. Disease control rate (DCR = CR+PR+SD) and objective remission rate (ORR = CR+PR) were calculated using Fisher exact probability and bilateral 95% confidence intervals were presented.

Safety analysis: descriptive statistical analysis was used to tabulate the AEs that occurred in this trial. laboratory test results were described as normal before the trial but abnormal after treatment and in relation to the trial drug when abnormal changes occurred.

Treatment protocol:

All subjects in this study were first tested for genes/proteins (HER2 protein, HER2FISH, PD-L1 protein 22C3, Claudin18.2, MMR) and received treatment in different groups according to gene/protein expression.

Group 1 HER protein positive 3+ or FISH amplification or HER protein 2+ but FISH amplification Initial treatment (4-6 cycles): IBI315 injection, oxaliplatin, capecitabine Group 2 Claudin18.2 protein-positive Initial treatment (4-6 cycles): PD-L1 monoclonal antibody, TST001 injection, oxaliplatin, capecitabine Group 3 Her protein and Claudin18.2 protein were negative Initial treatment (4-6 cycles): TQB2450 injection, Anrotinib, Oxaliplatin, Capecitabine Patients can undergo radical gastric cancer surgery or radical gastric cancer surgery + local treatment during the maintenance treatment phase if their condition is stable and after in-hospital MDT consultation. The duration of maintenance treatment was 2 years from the time of enrollment.

Principal Investigator: Luo Suxia, Li Ning Group leader unit: Henan Cancer Hospital

Conditions

• Gastric Cancer
• Gastroesophageal-junction Cancer

Interventions

DRUG

IBI315

IBI315 is a recombinant fully humanized anti-programmed death receptor 1 (PD-1) and humanized anti-human epidermal growth factor receptor 2 (HER2) bispecific antibody injection.

DRUG

Oxaliplatin

Oxaliplatin is a type of chemotherapy. It is used as a treatment for different types of cancer, including gastric cancer.

DRUG

Capecitabine

Capecitabine is a type of chemotherapy. It is used as a treatment for different types of cancer, including gastric cancer.

DRUG

TST001

TST001 is a high-affinity humanized monoclonal antibody targeting Claudin 18.2 with enhanced antibody-dependent cytotoxic (ADCC) and complement-dependent cytotoxic (CDC) activity, showing potent antitumor activity in xenograft assays.

DRUG

TQB2450

TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.

DRUG

Anrotinib

Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling.

Sponsors & Collaborators

• Henan Cancer Hospital

  lead OTHER_GOV

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-01-01

Primary Completion

2023-12-31

Completion

2024-10-01