Lenvatinib Plus Tislelizumab and CapeOX as First-Line Treatment for Advanced GC/GEJC With Positive PD-L1 and Low TMEscore

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 is a multicenter, prospective, phase II clinical study to evaluate the efficacy and safety of intensive treatment with lenvatinib plus tislelizumab and CapeOX as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma with PD-L1 positive and low TMEscore. A total of 92 subjects are randomly divided into study group and control group according to 1:1 ratio. Tislelizumab 200mg, iv, d1+ oxaliplatin 130mg/m2, iv, d1+ capecitabine 1000mg/m2, bid po, D1-14, q3w ± Lenvatinib 8mg, qd po regimen are received, respectively (3 weeks as a cycle, a maximum of 8 cycles of treatment). Then the maintenance treatment phase with tislelizumab ± lenvatinib is entered, and the specific dosage is the same as the treatment period. Effectiveness is assessed every 9 weeks (±7 days) until disease recurrence, metastasis, death, or loss of follow-up. The primary endpoint of this study was PFS, and secondary endpoints were OS, ORR, DoR, and DCR.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: lenvatinib and tislelizumab plus CapeOX chemotherapy; Drug: tislelizumab plus CapeOX chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 92
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wangjun Liao, MD, PhD; Phone Number: 86-20-62787731; Email: nfyyliaowj@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital, Southern Medical University
      • Contact: Wangjun Liao, MD, PhD; Phone Number: 86-20-62787731; Email: nfyyliaowj@163.com
      • Principal Investigator: Wangjun Liao, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intensive treatment of lenvatinib and tislelizumab plus CapeOX chemotherapy; Efficacy of lenvatinib and tislelizumab plus CapeOX as first-line treatment	Drug: lenvatinib and tislelizumab plus CapeOX chemotherapy; Tislelizumab 200mg, iv, d1+ oxaliplatin 130mg/m2, iv, d1+ capecitabine 1000mg/m2, bid po, D1-14, q3w + Lenvatinib 8mg, qd po regimen are received, respectively (3 weeks as a cycle, a maximum of 8 cycles of treatment). Then the maintenance treatment phase with tislelizumab + lenvatinib is entered, and the specific dosage is the same as the treatment period.
Active Comparator: Conventional treatment of tislelizumab plus CapeOX chemotherapy; Efficacy of tislelizumab plus CapeOX as first-line treatment	Drug: tislelizumab plus CapeOX chemotherapy; Tislelizumab 200mg, iv, d1+ oxaliplatin 130mg/m2, iv, d1+ capecitabine 1000mg/m2, bid po, D1-14, q3w regimen are received, respectively (3 weeks as a cycle, a maximum of 8 cycles of treatment). Then the maintenance treatment phase with tislelizumab is entered, and the specific dosage is the same as the treatment period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Defined as the time between the onset of PD or death when a patient first receives the study drug, whichever occurs first	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Defined as the proportion of patients who achieved complete response (CR) or partial response (PR)	3 years
Disease Control Rate (DCR)	Defined as the proportion of patients achieving CR, PR, or stable disease (SD).	3 years
Overall survival (OS)	Defined as the time between the patient's first receipt of the study drug to death	3 years
Duration of response (DoR)	Defined as the time between when a patient first reaches CR or PR to PD	3 years

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University
• Investigators: Study Director: Wangjun Liao, MD, PhD, Nanfang Hospital, Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: November 26, 2023
• First Submitted That Met QC Criteria: December 4, 2023
• First Posted (Actual): December 6, 2023

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 25, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Lenvatinib; Tislelizumab; First-line treatment; PD-L1 positive; GC/GEJC; TME score
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tislelizumab; Lenvatinib
• Other Study ID Numbers: NFEC-2023-478

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No