M108 Plus CAPOX Versus Placebo Plus CAPOX as First-line Treatment for Claudin (CLDN) 18.2-Positive, HER2-Negative, PD-L1 CPS<5, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma.

Phase 3

Recruiting

• Conditions: Locally Advanced Unresectable or Metastatic Gastric Cancer; Locally Advanced Unresectable or Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma
• Interventions: Drug: M108 monoclonal antibody; Drug: Placebo; Drug: Oxaliplatin; Drug: Capecitabine

• Registration Number: NCT06177041
• Lead Sponsor: FutureGen Biopharmaceutical (Beijing) Co., Ltd

Brief Summary

Gastric/GEJ adenocarcinoma, which is one of the major leading causes of cancer-related deaths worldwide, is a global challenge to human health. However, standard chemotherapy has limited efficacy in advanced gastric cancer, and there is an urgent need to explore and develop new therapeutic targets and combination therapy modalities. The main purpose of this study is to explore the efficacy of M108 monoclonal antibody plus capecitabine and oxaliplatin (CAPOX) versus placebo plus CAPOX as first-line treatment measured by progression free survival (PFS). This study will also evaluate safety, tolerability, pharmacokinetics and the immunogenicity profile of M108 monoclonal antibody, as well as its effects on quality of life.

Detailed Description

The aim of this phase 3, double-blind, randomized, placebo-controlled study is to explore the efficacy and safety of M108 monoclonal antibody plus chemotherapy versus placebo plus chemotherapy as first-line treatment for Claudin (CLDN) 18.2-Positive, HER2-Negative, PD-L1 CPS\<5, locally advanced or metastatic gastric/GEJ adenocarcinoma. Patients will be randomized in a 1:1 ration to receive M108 monoclonal antibody plus chemotherapy or placebo plus chemotherapy.

Study Timeline

• Study First Submitted: 2023-12-11
• Study First Submitted QC: 2023-12-11
• Study First Posted: 2023-12-20
• Study Start: 2023-12-25
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-25
• Last Update Posted: 2024-02-28
• Primary Completion: 2027-01-11
• Study Completion: 2027-04-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 486

Inclusion Criteria

1. Written informed consent
2. Histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma with no treatment previously. For patients with neoadjuvant/adjuant chemotherapy in the past, duration of last therapy to recurrence should be more than 6 months
3. At least 1 measurable site of the disease according to RECIST 1.1 criteria.
4. Positive CDLN 18.2 expression
5. Negative HER2 expression, PD-L1 CPS<5
6. ECOG performance status (PS) 0-1
7. Life expectancy > 3 months
8. Age ≥ 18 years and ≤75 years
9. Adequate haematological/ coagulation/ hepatic/ renal function
10. Men and women of childbearing age should agree to use effective contraception from the time they sign their informed consent until 3 months after the last dosing. Female subjects of childbearing age must have a negative blood beta-HCG test within 72 hours prior to first dosing.

Exclusion Criteria

1. Previous radiotherapy within 4 weeks prior to the start of study treatment. (if palliative radiotherapy was given to bone metastases and the patient recovered from acute toxicity was allowed).
2. Previous anti-tumor therapy within 4 weeks prior to the start of study treatment.
3. Previous major operation within 4 weeks prior to the start of study treatment.
4. Have a prior severe allergic reaction or intolerance to known components of M108 monoclonal antibodies or other monoclonal antibodies (including humanized or chimeric antibodies); Allergic or intolerant to any component of capecitabine, oxaliplatin, etc.
5. Subject who has been treated with CLDN18.2 monoclonal/bispecific antibodies, CLDN18.2 CAR-T, CLDN18.2 ADC and any therapies that target CLDN18.2.
6. Subject who is in pregnant or in lactation period.
7. Other clinically significant disease which may have adversely affected the safe delivery of treatment within this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
M108 plus CAPOX	Oxaliplatin	-
placebo plus CAPOX	Oxaliplatin	-
M108 plus CAPOX	M108 monoclonal antibody	-
placebo plus CAPOX	Placebo	-
placebo plus CAPOX	Capecitabine	-
M108 plus CAPOX	Capecitabine	-

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	From date of randomization to the date of disease progression, death or end of study, assessed up to 24 months	Compare PFS (Based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 by Independent Review Committee (IRC)) of patients treated with M108 monoclonal antibody or placebo plus CAPOX.

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability assessed by adverse events (AEs)	From date of randomization until 28+7 days after the last dose	An AE is any adverse medical event that occurs during a clinical study, whether or not related with medicinal product, including signs, symptoms, abnormal laboratory test results and diseases. The incidence and severity of AEs during the clinical study are recorded and analyzed.
Overall survival (OS)	From date of randomization to the date of death or end of study, assessed up to 24 months	Compare OS (Based on RECIST 1.1 by IRC) of patients treated with M108 monoclonal antibody or placebo plus CAPOX.

Trial Locations

Locations (1)

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China