Combination treatment for advanced gastric cancer with specific biomarkers

Tislelizumab Plus CapeOX ± Lenvatinib as First-Line Treatment for Advanced GC/GEJC With Positive PD-L1 and Low TMEscore: A Multi-center, Prospective, Phase II Study

This study is testing a new combination treatment for people with advanced gastric cancer who have certain biomarkers to see if it helps them live longer without their disease getting worse.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 92 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Nanfang Hospital, Southern Medical University (Academic / other)
• Drugs / interventions: fuquinitinib, chemotherapy, radiation, prednisone, tislelizumab, lenvatinib
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06157996 on ClinicalTrials.gov

What this trial studies

This phase II clinical study evaluates the safety and efficacy of a combination treatment involving lenvatinib, tislelizumab, and CapeOX chemotherapy as a first-line therapy for patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma that are PD-L1 positive and have a low tumor microenvironment score. The study involves 92 participants who are randomly assigned to receive either the combination treatment or a control regimen. Treatment cycles last three weeks, with effectiveness assessed every nine weeks until disease progression or other endpoints are met. The primary focus is on progression-free survival, with secondary outcomes including overall survival and response rates.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with histologically confirmed advanced gastric cancer or gastroesophageal junction adenocarcinoma that is PD-L1 positive and has a low TME score.

Not a fit: Patients who have received prior systemic antitumor therapy or those with a performance status above 2 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective first-line option for patients with advanced gastric cancer who meet specific biomarker criteria.

How similar studies have performed: Other studies have shown promise with similar combination therapies in advanced gastric cancer, but this specific approach is novel.

Eligibility criteria

Inclusion Criteria:

1. Patients voluntarily participated in the study, signed the informed consent, and had good compliance;
2. Age over 18 (including 18 years old), gender is not limited;
3. Histologically and/or cytologically confirmed advanced gastric cancer or gastroesophageal junction adenocarcinoma (stage IV);
4. Tumor with PD-L1 positive and low tumor microenvironment score (TMEscore)
5. Have not received systemic antitumor therapy before; Or have previously received adjuvant or neoadjuvant therapy (chemotherapy/radiotherapy) for the purpose of cure, and the time of tumor recurrence \> 6 months since the last treatment
6. ECOG performance status of 0-2 points;
7. Expected survival ≥12 weeks;
8. Blood test (without blood transfusion within 14 days) 1) Neutrophil absolute value ≥1.5×10\^9/L, platelet ≥100×10\^9/L, hemoglobin ≥90g/L); 2) Liver function test (aspartate aminotransferase and glutamate aminotransferase ≤3×ULN, bilirubin ≤1.5×ULN; In case of liver metastasis, AST and ALT≤5×ULN); 3) Renal function (serum creatinine ≤1.5×ULN, or creatinine clearance (CCr)≥60ml/min);
9. Men and women of childbearing age must use effective contraceptive methods.

Exclusion Criteria:

1. Previously received therapy that targets T cell co-stimulation or checkpoint pathways ,such as anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, etc.;
2. Previously received anti-vascular small-molecule targeted drug therapy, such as fuquinitinib, regofenib, etc.;
3. Received major surgery within 4 weeks prior to the first drug administration; radiotherapy, radiofrequency ablation and other investigational drugs for tumors within 2 weeks;
4. Received live vaccine within 4 weeks prior to the first drug administration (except inactivated viral vaccine for seasonal influenza);
5. A history of severe intolerance to drugs involved in the study (i.e., grade 4 toxicity of one of these drugs; Class 3-4 toxicity of other co-administered drugs is not excluded);
6. Known allergy to the study drug or any of its excipients;
7. HER2 positive gastric cancer or gastroesophageal junction adenocarcinoma;
8. The patient had other malignancies within the previous 5 years or at the same time (except cured basal cell carcinoma, stage I squamous cell carcinoma, in situ carcinoma, intramucosal carcinoma, and superficial bladder cancer);
9. Known brain or meningeal metastases;
10. Patients who are preparing for or have previously received an organ or bone marrow transplant;
11. A history of human immunodeficiency virus (HIV) infection;
12. A history of psychotropic substance abuse or drug use;
13. Condition that may interfere with the detection and management of suspected drug-related pulmonary toxicity, such as interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, or severe impairment of lung function;
14. Known active or suspected autoimmune disease (except for patients with stable disease at enrollment who do not require systemic immunosuppressive therapy);
15. Patients who required systemic corticosteroids (\> 10 mg/ day efficacy dose of prednisone) or other immunosuppressive agents within 2 weeks prior to initial administration or during the study period. However, adrenal hormone replacement therapy with topical or inhaled steroids, or a therapeutic dose of prednisone ≤ 10mg/ day in the absence of active autoimmune disease was permitted;
16. Any active infection that requires systematic anti-infective treatment occurs within 2 weeks prior to the first dose (expect prophylactic antibiotic therapy, such as for urinary tract infections or chronic obstructive pulmonary disease);
17. Active heart disease, including myocardial infarction, severe/unstable angina in the 6 months prior to treatment. Echocardiography showed that the left ventricular ejection fraction was less than 50%, indicating poor arrhythmia control.
18. Obvious clinical bleeding symptoms or obvious bleeding tendency and hemoptysis within 3 months prior to treatment. Or treatment of venous/venous thrombosis events within the preceding 6 months, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; Long-term anticoagulant therapy with warfarin or heparin, or long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day) is required;
19. Any other disease, a clinically significant metabolic abnormality, abnormal physical examination or abnormal laboratory examination, for which, in the investigator's judgment, there is reason to suspect that the patient has a disease or condition unsuitable for the use of the investigational agent;
20. Anything that, in the investigator's opinion, could put subjects receiving the study drug at risk, interfere with the study drug, subject safety assessment, or interpretation of the results;
21. Pregnant or lactating women or women who may become pregnant.

Where this trial is running

Guangzhou, Guangdong

• Nanfang Hospital, Southern Medical University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Wangjun Liao, MD, PhD

Conditions Gastric Cancer; Lenvatinib; Tislelizumab; First-line treatment; GC/GEJC; TME score; PD-L1 positive