Tislelizumab plus chemotherapy for advanced gastric, gastroesophageal, and esophageal squamous cancers in U.S. racial and ethnic minority patients

An Open-Label, Single-Arm, Phase 2 Study to Evaluate the Efficacy and Safety of Tislelizumab Plus Chemotherapy in a First-Line Setting for Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Adenocarcinoma and Esophageal Squamous Cell Carcinoma in US Racial and Ethnic Minority Patients

This will test whether adding tislelizumab to standard chemotherapy helps U.S. racial and ethnic minority patients with HER2-negative, PD-L1-positive unresectable or metastatic gastric, gastroesophageal, or esophageal squamous cell cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: BeOne Medicines (Industry-sponsored)
• Drugs / interventions: tislelizumab, chemotherapy, prednisone
• Locations: 1 site (Hialeah, Florida)
• Trial ID: NCT07554521 on ClinicalTrials.gov

What this trial studies

This is a Phase 2 interventional study giving the anti–PD-1 antibody tislelizumab together with standard chemotherapy (capecitabine or 5‑FU, oxaliplatin, and leucovorin) to adults with HER2‑negative, PD‑L1‑positive, unresectable or metastatic gastric/gastroesophageal adenocarcinoma or esophageal squamous cell carcinoma who self-identify as members of U.S. racial and ethnic minority groups. Participants must have no prior systemic therapy for advanced disease, an ECOG performance status of 0–1, and at least one measurable lesion per RECIST v1.1. The study will collect pharmacokinetics, safety, and anti-tumor activity data, with tumor response measured by RECIST criteria and safety monitored throughout treatment. Total participation may last up to about six years to capture longer-term outcomes and safety information.

Who should consider this trial

Good fit: Adults who self-identify as U.S. racial or ethnic minorities with histologically confirmed HER2-negative, PD-L1-positive unresectable or metastatic gastric/gastroesophageal adenocarcinoma or esophageal squamous cell carcinoma, ECOG ≤1, no prior systemic therapy for advanced disease, and at least one measurable lesion are ideal candidates.

Not a fit: Patients who are HER2-positive, PD-L1-negative, have received prior systemic therapy for advanced disease, have poor performance status, or have contraindications to immunotherapy or the planned chemotherapies may not receive benefit from this regimen.

Why it matters

Potential benefit: If successful, this approach could offer a more effective first-line option and improve outcomes for PD-L1-positive, HER2-negative advanced gastric, gastroesophageal, or esophageal squamous cancers in racial and ethnic minority patients.

How similar studies have performed: Other trials combining PD‑1 inhibitors with chemotherapy have shown benefit in advanced gastric and esophageal cancers, but this specific tislelizumab regimen and the targeted focus on U.S. racial and ethnic minority patients is less well studied.

Eligibility criteria

Inclusion Criteria:

* Self-identifies as a member of racial and/or ethnic minority populations as defined by the Food and Drug Administration (FDA), such as Black or African American, Hispanic or Latino, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander
* Histologically confirmed, locally advanced unresectable or metastatic gastric or gastroesophageal adenocarcinoma (GAC/GEA) or esophageal squamous cell carcinoma (ESCC)
* No previous systemic therapy for locally advanced unresectable or metastatic GAC/GEA or ESCC
* At least 1 measurable lesion per RECIST v1.1 as determined by investigator assessment
* Patients must have positive tumor programmed death-ligand 1 (PD-L1) expression. Documented PD-L1 results are acceptable
* Eastern Cooperative Oncology Group (ECOG) Performance Status score ≤ 1
* Adequate organ function as indicated by the following laboratory values ≤ 14 days prior to study treatment
* Women of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of tislelizumab and ≥ 180 days after the last dose of chemotherapy, and have a negative urine or serum pregnancy test ≤ 7 days prior to study treatment
* Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of tislelizumab and ≥ 180 days after the last dose of chemotherapy

Exclusion Criteria:

* Patient has squamous cell or undifferentiated or other histological type gastric cancer
* Active leptomeningeal disease or uncontrolled brain metastasis. Patients with equivocal findings or with confirmed brain metastases are eligible for enrollment provided that they are asymptomatic and radiologically stable without the need for corticosteroid treatment for ≥ 4 weeks before study treatment.
* Patients with evidence of esophageal/bronchial or esophageal/aorta fistula, or complete esophageal obstruction not amenable to treatment.
* Diagnosed with GAC/GEA with positive human epidermal growth factor receptor 2 (HER2). Results of the tumor HER2 testing must be known prior to study treatment
* Active autoimmune diseases or history of autoimmune diseases that may relapse Note: Patients with the following diseases are not excluded and may proceed to further screening:

  1. Controlled Type I diabetes
  2. Hypothyroidism (provided it is managed with hormone replacement therapy only)
  3. Controlled celiac disease
  4. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia)
  5. Any other disease that is not expected to recur in the absence of external triggering factors
* Any active malignancy ≤ 2 years before study treatment, with the exception of the specific cancer under investigation in this trial or any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast)
* Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (at least once a week) and/or diuretics within 7 days prior to study treatment (the cytological confirmation of any effusion is permitted)
* Have clinically significant bleeding (Common Terminology Criteria for Adverse Events (CTCAE) ≥ Grade 2) from the GI tract within 1 month prior to study treatment
* Have a history of gastrointestinal (GI) perforation (CTCAE ≥ Grade 2) and/or fistulae (including prior gastric fistula operation) within 6 months prior to study treatment
* Have a clinically significant bowel obstruction (CTCAE ≥ Grade 2)
* Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before study treatment.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Where this trial is running

Hialeah, Florida

• Bioresearch Partners Holding Hialeah Hospital — Hialeah, Florida, United States (Recruiting)

Study contacts

• Study coordinator: Study Director

Conditions Advanced Unresectable Gastric Adenocarcinoma; Esophageal Squamous Cell Carcinoma; Advanced Gastroesophageal Adenocarcinoma