Comparing the Efficacy of Sintilimab Plus Nab-POF Regimen, Sintilimab Plus XELOX Chemotherapy, and Lenvatinib, Sintilimab Plus XELOX Chemotherapy in the Treatment of HER2-negative, Metastatic Gastric Cancer

Official title

A Multicenter, Prospective, Open-label, Randomized Controlled, Phase II Clinical Trial Comparing the Efficacy of Sintilimab Plus Nab-POF Regimen, Sintilimab Plus XELOX Chemotherapy, and Lenvatinib, Sintilimab Plus XELOX Chemotherapy in the Treatment of HER2-negative, Metastatic Gastric Cancer

Overview

This trial is a prospective, open, randomized, phase II clinical study. It compares the current first-line treatment for advanced gastric cancer in phase II clinical trials, with the best efficacy being the combination of orient-16 study with sintilimab and XELOX regimen. The purpose of this study is to evaluate whether adding anti-angiogenic drugs or chemotherapy drugs on the basis of two-drug chemotherapy regimen (XELOX regimen) and PD-1 monoclonal antibody can improve efficacy for advanced gastric cancer.

Interventions

• Drug Sintilimab, oxalipaltin, 5FU,Nab-paclitaxel,lenvatinib
  Patients were randomized in a 1:1:1 ratio to three treatment groups: control group A: pembrolizumab combined with XELOX regimen, the regimen was repeated every 3 weeks, and tumor efficacy was evaluated every 2 treatment cycles. Group B: treatment regimen was pembrolizumab combined with Nab-POF regimen, the regimen was repeated every 2 weeks, and tumor efficacy was evaluated every 3 treatment cycles. Group C: treatment regimen was pembrolizumab combined with XELOX regimen and lenvatinib, the regi

Primary outcome measures

• Objective response rate [Time frame: the duration from the date of randomization to any documented tumor progression or death due to any cause，assessed up to 24 months]

Secondary outcome measures (3)

• Overall survival [Time frame: the duration from the date of randomization to the date of death due to any cause,assessed up to 48 months]
• Progression-free survival time [Time frame: the duration from the date of randomization to any documented tumor progression or death due to any cause, assessed up to 48 months]
• Disease control rate [Time frame: the duration from the date of randomization to any documented tumor progression or death due to any cause, assessed up to 24 months]

Eligibility criteria

Inclusion criteria

• Males or females aged over than 18 years
• Histologically or cytologically confirmed gastric adenocarcinoma (including GEJ adenocarcinoma)
• Presence of measurable lesions(RECIST 1.1)
• Newly diagnosed patients; or patients with recurrence after surgery, who have been off adjuvant chemotherapy for at least 6 months and have not received any anti-cancer treatment within the past 6 months
• ECOG PS score: 0-1
• Expected survival over than 3 months
• Normal major organ function or reserve, meeting the following criteria (determined by laboratory test data within 7 days (inclusive) before screening): HB ≥90 g/dL, ANC ≥1.5×109/L, PLT ≥100×109/L; BIL<1.5×ULN, ALT and AST <2.5×ULN, if with metastases to liver, then ALT, AST <5×ULN; serum Cr≤1×ULN, endogenous creatinine clearance >50 mL/min (calculated by CK formula), international normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN, if the subject is receiving anticoagulant therapy, PT should be within the intended range of the anticoagulant drug
• Subjects who voluntarily participate in this study, sign the informed consent form, have good compliance, and cooperate with follow-up

Exclusion criteria

• Histopathological assessment of HER2 positivity (immunohistochemistry 3+ or immunohistochemistry 2+ and FISH positive)
• Known dMMR/MSI-H
• History of other malignant neoplasms within 3 years prior to enrollment, except for cured cervical carcinoma in situ or basal cell carcinoma
• Presence of brain metastases to meninges
• Malignant pleural or peritoneal effusion
• Presence of gastrointestinal obstruction, gastrointestinal haemorrhage (fecaloccult blood +++ or higher), or perforation
• Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2, CD137, CTLA-4 antibodies, or any other antibody or drug specifically targeting T-cell co-stimulatory or checkpoint pathways
• Subjects with active or history of autoimmune diseases that might relapse (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disorder, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or high-risk patients (e.g., those requiring immunosuppression after organ transplant), except for those with vitiligo, psoriasis, alopecia, or Graves' disease that have not required systemic treatment within the past 2 years, or hypothyroidism requiring only thyroid hormone replacement therapy, or Type I diabetes mellitus requiring only insulin replacement therapy
• Current interstitial lung disorder or pneumonia, pulmonary fibrosis, acute lung disorder, or radiation pneumonitis
• Participation in other drug clinical studies within 4 weeks prior to the first dose (based on the use of investigational drug), except observational (non-interventional) clinical studies
• Use of immunosuppressant drugs within 4 weeks prior to the first dose of study treatment, excluding nasal, inhaled, or other topical glucocorticoids or physiological doses of systemic glucocorticoids (i.e., no more than 10 mg/day of prednisone or equivalent dose of other glucocorticoids), or short-term (no more than 7 days) use of glucocorticoids for the prevention or treatment of non-autoimmune allergic diseases
• Receipt of live attenuated vaccines within 4 weeks prior to the first dose of study treatment or planned immunization during the study period. Note: Inactivated seasonal influenza vaccines for injection are allowed within 4 weeks prior to the first dose; however, live attenuated influenza vaccines are not allowed.
• Major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study treatment or anticipated need for major surgery (not related to this study) during the study treatment period.
• History of human immunodeficiency virus (HIV) infection (i.e., HIV antibody positive), or other acquired or congenital immunodeficiency diseases, or history of organ transplant or stem cell transplant
• Active chronic hepatitis B or active hepatitis C; hepatitis B virus carriers, but patients with stable hepatitis B viral loads after drug therapy (HBV DNA ≤ 200 IU/mL or copy number < 1000 copies/mL), and patients who have cleared hepatitis C virus (HCV RNA negative) are eligible for enrollment
• Known active pulmonary tuberculosis
• Patients with severe infection within 4 weeks before the first dose, or active infection requiring oral or vein antibiotic therapy within 2 weeks before the first dose
• Symptomatic congestive cardiac failure (New York Heart Association Class II-IV) or symptomatic or poorly controlled arrhythmia
• Uncontrolled hypertension (blood pressure systolic ≥160 mmHg or blood pressure diastolic ≥100 mmHg) despite standard treatment
• Any arterial embolism event within 6 months before enrollment, including myocardial infarction, angina unstable, cerebrovascular accident, or transient ischemic attack
• History of deep vein thrombosis, pulmonary embolism, or any other severe embolism within 3 months before enrollment (thrombosis originating from implanted venous access port or catheter, or superficial vein thrombosis is not considered as "severe" thromboembolism)
• History of definite neurological or mental disorder: such as epilepsy, dementia, poor compliance, or peripheral nervous system disorders
• Alcohol dependence or history of drug addiction or drug abuse within the past year
• Pregnant or lactating women,women of childbearing potential who are not taking adequate contraception
• Other acute or chronic disease, mental disorder, or laboratory test abnormality that might lead to the following results: increased risk associated with study participation or study drug administration, or interference with the interpretation of study results, and the investigator judges the patient to be ineligible for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Fudan University Cancer Hospital — Shanghai
• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT06748508 · MGC-NabPOF

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗