Lenvatinib with nivolumab and chemotherapy for metastatic gastric cancer with malignant ascites
A Clinical Trial Evaluating the Efficacy and Safety of Lenvatinib, Nivolumab, and Chemotherapy in Metastatic Gastric Cancer With Malignant Ascites.
This trial tests whether adding lenvatinib to nivolumab plus chemotherapy helps people with metastatic gastric or gastroesophageal junction adenocarcinoma who have peritoneal metastases and significant malignant ascites.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 61 (estimated) |
| Ages | 19 Years and up |
| Sex | All |
| Sponsor | Asan Medical Center Academic / other |
| Drugs / interventions | lenvatinib, chemotherapy, immunotherapy, nivolumab |
| Locations | 1 site (Seoul) |
| Trial ID | NCT07149090 on ClinicalTrials.gov |
What this trial studies
This is a Phase 1/2 interventional trial testing the safety and activity of adding the oral anti-angiogenic drug lenvatinib to nivolumab plus standard chemotherapy in patients with metastatic gastric or gastroesophageal junction adenocarcinoma who have peritoneal metastases and grade ≥2 malignant ascites. Eligible patients must have PD-L1 combined positive score (CPS) ≥5 and adequate organ function, ECOG 0–1, and life expectancy >4 months. The study will measure safety, response rates, control of ascites, and survival outcomes to see if the combination improves outcomes compared with historical expectations for this high-risk subgroup. The trial is conducted at Asan Medical Center in Seoul and includes dose-finding (Phase 1) followed by an expanded efficacy cohort (Phase 2).
Who should consider this trial
Good fit: Adults (over 19) with newly diagnosed metastatic, unresectable, or recurrent gastric/GEJ adenocarcinoma who have radiologically confirmed peritoneal metastasis with grade ≥2 malignant ascites, PD-L1 CPS ≥5, ECOG 0–1, and adequate organ and marrow function are ideal candidates.
Not a fit: Patients without peritoneal metastasis or significant ascites, those who do not meet PD-L1 or organ-function criteria, those with neuropathy or poor performance status, or with life expectancy ≤4 months are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, the combination could better control malignant ascites and improve survival for gastric cancer patients who do poorly with current first-line immunotherapy plus chemotherapy.
How similar studies have performed: Nivolumab plus chemotherapy has already improved survival in broad first-line gastric cancer populations (CheckMate-649), and anti‑VEGF approaches have shown promise for managing malignant ascites, but combining lenvatinib with nivolumab plus chemotherapy specifically in this high-ascites subgroup is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Newly diagnosed pathologically proven metastatic, unresectable or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma
2. Positive for peritoneal metastasis and grade ≥ 2 malignant ascites as confirmed by computed tomography (CT)
3. PD-L1 combined positive score of ≥5 based on the 28-8 assay
4. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
5. Age \> 19 years at time of study entry
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Life expectancy of \> 4 months
8. Body weight \> 30kg
9. No existing neuropathy
10. Adequate normal organ and marrow function as defined below:
* Hemoglobin ≥9.0 g/dL
* Absolute neutrophil count (ANC) 1.5 x (\> 1500 per mm3)
* Platelet count ≥100 (or 75) x 109/L (\>75,000 per mm3)
* Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN)
* AST (SGOT)/ALT (SGPT) ≤2.5 x institutional ULN
* Measured creatinine clearance (CL) \> 40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance:
11. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre- menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
12. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
Exclusion Criteria:
1. Disease progression within 6 months after completion of adjuvant chemotherapy.
2. Participation in another clinical study with an investigational product during the last 2 weeks
3. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
4. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
5. Major surgical procedure within 28 days prior to the first dose
6. Unable to take medication orally
7. Gastrointestinal bleeding
8. Impaired bowel absorption
9. History of allogenic organ transplantation
10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent
11. History of another primary malignancy except for
* Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose and of low potential risk for recurrence
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
* Adequately treated carcinoma in situ without evidence of disease
12. History of active primary immunodeficiency
13. Active infectious disease
14. Tuberculosis (based on clinical history, physical examination, radiographic findings, and TB testing in line with local practice)
15. Hepatitis B (known positive HBV surface antigen (HBsAg) result)
16. Hepatitis C (patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA)
17. Human immunodeficiency virus (positive HIV 1/2 antibodies)
18. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible.
19. Female patients who are pregnant or breastfeeding, as well as male or female patients of reproductive potential who are not willing to use effective contraception from the time of screening until 5 months following the final dose of lenvatinib.
20. Known allergy or hypersensitivity to the investigational drug or any of its components.
21. Patients with known deficiency of dihydropyrimidine dehydrogenase (DPD).
22. Patients with known hereditary problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
Where this trial is running
Seoul
- Asan Medical Center — Seoul, South Korea (Recruiting)
Study contacts
- Study coordinator: Hyung-Don Kim
- Email: kimhdmd@amc.seoul.kr
- Phone: 82-2-3010-0236
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.