Combination treatment for advanced gastric cancer with low PD-L1 expression

A Single-arm, Multicenter Exploratory Clinical Trial of Anlotinib Combined With TQB2450 and the SOX Regimen as First-line Treatment for Advanced Gastric Cancer With Low PD-L1 Expression

This study tests if a new combination of treatments can help people with advanced gastric cancer that has low PD-L1 levels feel better compared to standard treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 37 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First Affiliated Hospital of Zhengzhou University (Academic / other)
• Drugs / interventions: anlotinib, chemotherapy, prednisone
• Locations: 1 site (Zhengzhou, Henan)
• Trial ID: NCT06939452 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of anlotinib combined with TQB2450 and the SOX regimen as a first-line treatment for patients with advanced gastric cancer that has low PD-L1 expression. The study involves a single-arm, multicenter approach, where participants will receive the combination therapy, and their outcomes will be compared to real-world data from patients receiving standard treatment. The goal is to determine if this new combination can improve treatment outcomes for this specific patient population.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18-75 with unresectable locally advanced or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma.

Not a fit: Patients with HER2-positive gastric cancer or those who have received prior local therapy for their measurable lesions 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 who have low PD-L1 expression.

How similar studies have performed: While there have been studies on similar combination therapies, this specific approach targeting low PD-L1 expression in advanced gastric cancer is relatively novel.

Eligibility criteria

Inclusion Criteria:

* 1. Willing and able to provide written informed consent and comply with study procedures.
* 2. Histologically or cytologically confirmed HER2-negative (or HER2 status undetermined) unresectable locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (including signet ring cell carcinoma, mucinous adenocarcinoma, and hepatoid adenocarcinoma variants).
* 3. Disease recurrence \>6 months after completion of (neo)adjuvant chemotherapy or radiotherapy.
* 4. At least one measurable or evaluable lesion according to RECIST v1.1 criteria. Measurable lesions must not have received prior local therapy (e.g., radiotherapy); however, lesions within previously irradiated fields may be designated as target lesions if documented progression is demonstrated per RECIST v1.1.
* 5. Age 18-75 years.
* 6. ECOG performance status 0-1.
* 7. Life expectancy ≥3 months.
* 8. Organ Function Requirements and Laboratory Test Criteria During Screening (1) Complete Blood Count (CBC) Criteria： Hemoglobin (Hb): ≥ 90 g/L (no blood transfusion within 14 days) Absolute Neutrophil Count (ANC): ≥ 1.5 × 10⁹/L Platelet Count (PLT): ≥ 100 × 10⁹/L (no use of interleukin-11 \[IL-11\] or thrombopoietin \[TPO\] within 14 days) White Blood Cell Count (WBC): ≥ 4.0 × 10⁹/L (no granulocyte colony-stimulating factor \[G-CSF\] administration within 14 days) (2) Biochemical Panel Requirements: Total Bilirubin (TBIL): ≤ 1.5 × ULN (upper limit of normal),Alanine Aminotransferase (ALT) \& Aspartate Aminotransferase (AST): ≤ 2.5 × ULN,Serum Creatinine (Cr): ≤ 1.5 × ULN or Creatinine Clearance (CrCl): ≥ 60 mL/min (calculated by Cockcroft-Gault formula),Serum Albumin: ≥ 25 g/L (2.5 g/dL) For Subjects with Hepatic Metastases:Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT): ≤ 5 × ULN，White Blood Cell Count (WBC): ≥ 4 × 10⁹/L，Platelet Count (PLT): ≥ 100 × 10⁹/L (without transfusion support)， Absolute Neutrophil Count (ANC): ≥ 1.5 × 10⁹/L (without granulocyte colony-stimulating factor \[G-CSF\] therapy) (3) Cardiac Function Assessment (Echocardiography)：Left Ventricular Ejection Fraction (LVEF): ≥ 50% (or above institutional lower limit of normal) (4) Coagulation Profile：International Normalized Ratio (INR) or Prothrombin Time (PT): ≤ 1.5 × ULN
* 9. Women of reproductive age must use effective contraception during the study period, after the last dose, and for at least 6 months following chemotherapy. It is recommended to start using contraception at least 3 months before the administration of the investigational drug; unsterilized males must also be required to use effective contraception for at least 6 months during the study period, after the last dose, and following chemotherapy. It is recommended to start using contraception at least 3 months before the administration of the investigational drug.
* 10. PD-L1 combined positive score ( CPS) \<5

Exclusion Criteria:

* 1. Prior treatment with anlotinib hydrochloride or any immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies);
* 2. History of immunodeficiency disorders, including HIV infection, other acquired or congenital immunodeficiency diseases, or prior organ transplantation;
* 3. Active hepatitis B or C infection, or active pulmonary tuberculosis;
* 4. CT-confirmed ulcerative lesions or fecal occult blood positivity;
* 5. History of clinically significant bleeding (excluding epistaxis) within 1 month prior to enrollment;
* 6. Previous allogeneic bone marrow or solid organ transplantation;
* 7. Interstitial lung disease including idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or CT-confirmed active pneumonia;
* 8. Administration of live attenuated vaccines within 4 weeks before study initiation or anticipated during the study through 5 months post-treatment;
* 9. Systemic corticosteroids (\>10 mg/day prednisone equivalent) or immunosuppressive therapy within 2 weeks prior to study initiation (inhaled or topical corticosteroids are permitted);
* 10. Known symptomatic CNS metastases or leptomeningeal carcinomatosis. Patients with previously treated CNS metastases may be eligible if neurologically stable for ≥4 weeks without steroids or anticonvulsants;
* 11. Conditions impairing oral drug absorption (e.g., dysphagia, chronic diarrhea, or intestinal obstruction);
* 12. Grade ≥2 peripheral neuropathy per NCI CTCAE v5.0;
* 13. Active infections requiring systemic antibiotics within 14 days prior to study entry;
* 14. Hepatic tumor burden exceeding 50% of total liver volume;
* 15. Bone metastases with impending spinal cord compression risk;
* 16. Uncontrolled comorbidities including:
* Poorly controlled hypertension (SBP ≥150 mmHg or DBP ≥100 mmHg despite antihypertensives)
* Grade ≥2 myocardial ischemia, myocardial infarction, or arrhythmias (QTc ≥480 ms)
* NYHA Class III-IV heart failure or LVEF \<50% by echocardiography
* Uncontrolled active infections
* Decompensated liver cirrhosis or active hepatitis
* Uncontrolled diabetes (FBG \>10 mmol/L)
* Proteinuria ≥++ on dipstick or confirmed 24-hour urinary protein \>1.0 g
* 17. Non-healing wounds or fractures;
* 18. Coagulopathy (INR \>1.5 or aPTT \>1.5×ULN), bleeding diathesis, or requiring therapeutic anticoagulation:
* Known bleeding disorders (hemophilia, coagulopathies) or thrombocytopenia
* Hemoptysis (\>2.5 mL/day) within 2 months
* Clinically significant bleeding within 3 months (GI bleeding, hemorrhagic ulcers, etc.)
* Chronic anticoagulation (warfarin/heparin) or antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day)
* 19. Major surgical procedures within 4 weeks prior to study or anticipated during treatment;
* 20. History within 6 months of:
* GI perforation/fistula
* Arterial/venous thromboembolism (excluding stable cerebral infarcts)
* 21. Clinically significant pleural/peritoneal effusions requiring intervention (asymptomatic minimal effusions not requiring treatment may be permitted);
* 22. Severe malnutrition;
* 23. Active substance abuse or psychiatric disorders impairing compliance;
* 24. Other active malignancies except:
* Curatively treated malignancies with \>2 year disease-free interval
* Adequately treated non-melanoma skin cancer or lentigo maligna
* Carcinoma in situ with complete resection
* 25. Pregnancy or lactation;
* 26. Any condition deemed by investigators to compromise patient safety or study integrity;
* 27. Participation in other clinical trials within 30 days prior to enrollment or planned during study period.

Where this trial is running

Zhengzhou, Henan

• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Recruiting)

Study contacts

• Principal investigator: Yongxu Jia — The First Affiliated Hospital of Zhengzhou University
• Study coordinator: Yongxu Jia

Conditions Advanced Gastric or Gastroesophageal Junction Adenocarcinoma