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

NCT06157996 | Recruiting Phase 2

• 1 other identifier: NFEC-2023-478
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastric Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Overall survival (OS)

  3 years

• Objective Response Rate (ORR)

  3 years

• Disease Control Rate (DCR)

  3 years

• Duration of response (DoR)

  3 years

Study Arms (2)

Intensive treatment of lenvatinib and tislelizumab plus CapeOX chemotherapy

EXPERIMENTAL

Efficacy of lenvatinib and tislelizumab plus CapeOX as first-line treatment

Drug: lenvatinib and tislelizumab plus CapeOX chemotherapy

Conventional treatment of tislelizumab plus CapeOX chemotherapy

ACTIVE COMPARATOR

Efficacy of tislelizumab plus CapeOX as first-line treatment

Drug: tislelizumab plus CapeOX chemotherapy

Interventions

lenvatinib and tislelizumab plus CapeOX chemotherapy DRUG

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.

Intensive treatment of lenvatinib and tislelizumab plus CapeOX chemotherapy

tislelizumab plus CapeOX chemotherapy DRUG

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.

Conventional treatment of tislelizumab plus CapeOX chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients voluntarily participated in the study, signed the informed consent, and had good compliance;
• Age over 18 (including 18 years old), gender is not limited;
• Histologically and/or cytologically confirmed advanced gastric cancer or gastroesophageal junction adenocarcinoma (stage IV);
• Tumor with PD-L1 positive and low tumor microenvironment score (TMEscore)
• 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
• ECOG performance status of 0-2 points;
• Expected survival ≥12 weeks;
• 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);
• Men and women of childbearing age must use effective contraceptive methods.

You may not qualify if:

• 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.;
• Previously received anti-vascular small-molecule targeted drug therapy, such as fuquinitinib, regofenib, etc.;
• Received major surgery within 4 weeks prior to the first drug administration; radiotherapy, radiofrequency ablation and other investigational drugs for tumors within 2 weeks;
• Received live vaccine within 4 weeks prior to the first drug administration (except inactivated viral vaccine for seasonal influenza);
• 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);
• Known allergy to the study drug or any of its excipients;
• HER2 positive gastric cancer or gastroesophageal junction adenocarcinoma;
• 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);
• Known brain or meningeal metastases;
• Patients who are preparing for or have previously received an organ or bone marrow transplant;
• A history of human immunodeficiency virus (HIV) infection;
• A history of psychotropic substance abuse or drug use;
• 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;
• Known active or suspected autoimmune disease (except for patients with stable disease at enrollment who do not require systemic immunosuppressive therapy);
• 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;

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

lenvatinib; tislelizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Wangjun Liao, MD, PhD

  Nanfang Hospital, Southern Medical University

  STUDY DIRECTOR

Central Study Contacts

Wangjun Liao, MD, PhD

CONTACT

86-20-62787731; nfyyliaowj@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2023
• First Posted: December 6, 2023
• Study Start: June 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)