Treatment for advanced gastric cancer after previous immunotherapy

Efficacy and Safety of Serplulimab, Lenvatinib, and Paclitaxel in the Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma After First-line Immunotherapy: a Prospective, Single-armed Clinical Trial

This study is testing a new combination of treatments for people with advanced stomach cancer who have already tried immunotherapy to see if it helps them feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 59 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Qilu Hospital of Shandong University (Academic / other)
• Drugs / interventions: lenvatinib, chemotherapy, immunotherapy, Serplulimab
• Locations: 7 sites (Jinan, Shandong and 6 other locations)
• Trial ID: NCT05585580 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the effectiveness of a combination of Serplulimab, Lenvatinib, and Paclitaxel in patients with advanced gastric or gastroesophageal junction adenocarcinoma who have previously undergone immunotherapy. The study is designed as a prospective, single-arm, multicenter trial, focusing on patients who have shown a positive response to prior PD-1/PD-L1 inhibitor therapy. Participants will receive the treatment and be monitored for outcomes related to disease progression and overall response. The trial aims to provide insights into the efficacy of this combination therapy in a challenging patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-75 with confirmed advanced gastric or gastroesophageal junction adenocarcinoma who have previously received immunotherapy.

Not a fit: Patients who have not undergone prior immunotherapy or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new effective option for patients with advanced gastric cancer who have not responded to first-line immunotherapy.

How similar studies have performed: While this approach is novel in combining these specific agents for this indication, similar studies have shown promise in treating advanced cancers with immunotherapy and targeted therapies.

Eligibility criteria

Inclusion Criteria:

1. 18-75 years old, gender is not limited;
2. Histologically or cytologically proven metastatic or locally advanced gastric or gastroesophageal junction adenocarcinoma
3. Programmed death-ligand 1 (PD-L1) positive subjects (CPS ≥ 1), or those who have achieved objective response to first-line Programmed death-1 (PD-1)/PD-L1 inhibitor therapy， or previous first-line PD-1/PD-L1 inhibitor therapy Treatment of PFS ≥ 6 months;
4. Prior chemotherapy, surgery, radiotherapy, or immunotherapy-related toxicity (excluding alopecia) has resolved to CTCAE ≤ grade 1;
5. Has measurable disease as determined by RECIST 1.1；
6. Subjects who can provide tissue samples (preferably freshly obtained tumor tissue before second-line therapy) for central laboratory testing for PD-L1 expression level determination；
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
8. Adequate organ function:

   1. Blood routine (no blood transfusion within 14 days before treatment, no granulocyte colony-stimulating factor, no correction with other drugs) i. Neutrophil count (NE)\>1.5\*109/L; ii. Hemoglobin count (HGB) \> 90 g/L; iii. Platelet count (PLT)\>100\*109/L;
   2. Coagulation function (no blood product transfusion within 14 days before treatment) i. International Normalized Ratio (INR) or Prothrombin Time (PT)≤1.5\*Upper Limit of Normal (ULN);
   3. Blood biochemistry (liver and kidney function) i. Creatinine clearance ≥50 mL/min; ii. Total bilirubin (TBIL)≤1.5×ULN; iii. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP)≤2.5\*ULN; iv. Albumin \> 2.7 g/dL
9. The urine protein of the patient is less than or equal to 1+;
10. According to the judgment of the investigator, the life expectancy is ≥6 months;
11. Able and willing to give written informed consent and has signed the informed consent form (ICF), prior to performance of any trial activities.
12. Female patients must be surgically sterilized females, postmenopausal, or using some form of highly effective contraception during treatment and within 12 weeks after treatment; male patients must be surgically sterilized men, or during treatment and 6 months after treatment effective contraceptive method

Exclusion Criteria:

1. Human epidermal growth factor receptor 2 (HER2) positive;
2. History of treatment with multi-target small molecule inhibitors such as lenvatinib or paclitaxel drugs;
3. Received systemic therapy (including chemotherapy, immunotherapy or targeted therapy) or local therapy (including surgery, radiotherapy) for advanced disease within 14 days before enrollment;
4. Hypertension that is difficult to control by drugs (systolic blood pressure ≥ 160 mmHg and diastolic blood pressure ≥ 90 mmHg);
5. Patients with brain metastases, cancerous meningitis, spinal cord compression, or diseases of the brain or leptomeninges found in imaging CT or MRI examinations during screening;
6. Associated with refractory pleural effusion or ascites, such as pleural effusion or ascites that requires puncture and drainage within 2 weeks before the first administration;
7. Have other malignancies except cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors (Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading basement membrane));
8. Allergy to any study drug or excipients;
9. Chronic hepatitis B or HBV carriers with chronic hepatitis B virus (HBV) DNA exceeding 500 IU/mL, or patients with active hepatitis C virus (HCV) infection;
10. Presence of any active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, thyroid function Hyperthyroidism, hypothyroidism), or a known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation, or other investigators' assessment that they have an impact on the study treatment;
11. Long-term heavy use of hormones or use of other immunomodulators;
12. Active infection;
13. Have been vaccinated with live or attenuated vaccines within 30 days before the first dose, or plan to receive live or attenuated vaccines during the study period, excluding the new crown vaccine;
14. Arterial/venous thrombotic events within 6 months, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism;
15. Severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, or stent placement within 6 months before enrollment; poorly controlled arrhythmia; according to the New York Heart Association (NYHA) criteria, III to IV Grade 1 cardiac insufficiency, or echocardiography showed left ventricular ejection fraction (LVEF) \<50%;
16. History of interstitial lung disease or uncontrolled systemic disease, including diabetes, acute lung disease, etc.;
17. Known human immunodeficiency virus (HIV) infection;
18. Any major surgery requiring general anesthesia has been performed within ≤ 28 days before the first dose;
19. There is an underlying medical condition or alcohol/drug abuse or dependence that is not conducive to the administration of the study drug, or may affect the interpretation of the results, or put the patient at a high risk of treatment complications;
20. Participated in other therapeutic clinical studies.

Where this trial is running

Jinan, Shandong and 6 other locations

• Qilu hospital of Shandong univertisy — Jinan, Shandong, China (Recruiting)
• Shandong Provincial Hospital Affiliated to Shandong First Medical University — Jinan, Shandong, China (Recruiting)
• The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital) — Jinan, Shandong, China (Recruiting)
• The Affiliated Hospital of Qingdao University — Qingdao, Shandong, China (Recruiting)
• Qingdao Municipal Hospital（Group） — Qingdao, Shandong, China (Recruiting)
• Yantai Yuhuangding Hospital — Yantai, Shandong, China (Not_yet_recruiting)
• Linyi Cancer Hospital — Linyi, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Lian Liu — Qilu hospital of Shandong univertisy
• Study coordinator: Lian Liu

Conditions Advanced Gastric or Gastroesophageal Junction Adenocarcinoma