M108 plus chemotherapy for advanced gastric cancer treatment

A Phase 3, Multi-Center, Double-Blind, Randomized, Efficacy and Safety Study of M108 Monoclonal Antibody 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.

This study is testing if adding a new drug called M108 to standard chemotherapy can help people with advanced stomach cancer live longer and feel better.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 486 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: FutureGen Biopharmaceutical (Beijing) Co., Ltd (industry)
• Drugs / interventions: CAR-T, chemotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06177041 on ClinicalTrials.gov

What this trial studies

This phase 3, double-blind, randomized, placebo-controlled study aims to evaluate the efficacy and safety of the M108 monoclonal antibody combined with capecitabine and oxaliplatin (CAPOX) compared to a placebo plus CAPOX in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. The study focuses on patients who are Claudin 18.2-positive, HER2-negative, and have a PD-L1 CPS of less than 5. Participants will be monitored for progression-free survival, safety, tolerability, pharmacokinetics, immunogenicity, and quality of life. The goal is to find a more effective first-line treatment option for this challenging cancer type.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma who have not received prior treatment and meet specific biomarker criteria.

Not a fit: Patients with HER2-positive tumors or those with a PD-L1 CPS of 5 or greater may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced gastric cancer, potentially improving survival rates and quality of life.

How similar studies have performed: Other studies have shown promise in targeting Claudin 18.2 in gastric cancer, but this specific combination approach is relatively novel.

Eligibility criteria

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.

Where this trial is running

Beijing, Beijing Municipality

• Beijing Cancer Hospital — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Zhaoyu Jin, Ph.D

Conditions: Locally Advanced Unresectable or Metastatic Gastric Cancer, Locally Advanced Unresectable or Metastatic Gastroesophageal Junction Adenocarcinoma