A Prospective, Single-Arm, Phase Ⅱ Clinical Trial Evaluating Fruquintinib in Combination With Paclitaxel for Injection (Albumin-bound) and Iparomlimab and Tuvonralimab Injection as Second-Line Therapy in Advanced Gastric Cancer Patients Previously Received Immunotherapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 68
- 试验地点
- 1
- 主要终点
- Progress-free Survival(PFS)
研究概览
简要总结
Immunotherapy has established the new standard for first-line treatment of advanced or metastatic gastric cancer. However, current second-line options-predominantly consisting of targeted therapy plus chemotherapy or chemotherapy alone-confer only modest clinical benefit. Notably, pivotal phase III second-line trials (REGARD, RAINBOW, RAINBOW-Asia, FRUTIGA) exclusively enrolled patients who progressed on chemotherapy regimens; thus, high-quality evidence guiding second-line treatment specifically for immunotherapy-refractory patients remains scarce, representing a significant unmet medical need.
Anti-angiogenic agents have demonstrated capacity to ameliorate the hypoxic, immunosuppressive tumor microenvironment while exerting synergistic anti-tumor effects when combined with immune checkpoint inhibitors. Exploratory studies evaluating immunotherapy combined with anti-angiogenic therapy plus chemotherapy in advanced gastric cancer patients after first-line failure have yielded encouraging efficacy signals (NCT03966118, NCT04982276), with objective response rates of 30-40% and median progression-free survival approaching 6 months.
Based on this, the investigators aim to evaluate the efficacy and safety profile of fruquintinib combined with nab-paclitaxel and Iparomlimab and Tuvonralimab Injection (a novel bispecific antibody) as second-line treatment for patients with advanced gastric cancer who have experienced disease progression during or after first-line immunotherapy-containing regimens.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathologically or cytologically confirmed diagnosis of gastric cancer (GC) or gastroesophageal junction (GEJ) cancer.
- •Failure of first-line treatment with PD-1/PD-L1 inhibitors
- •With measurable lesions according to RECIST 1.1 criteria.
- •ECOG performance status of 0-1
- •Expected survival ≥3 months;
- •Major organ functions meet the following requirements :
- •Absolute neutrophil count (ANC) ≥ 1,500/mm³ (1.5 × 10⁹/L) (no growth factors used within 14 days).
- •Platelet count (PLT) ≥ 100,000/mm³ (100 × 10⁹/L) (no correction therapy used within 7 days).
- •Hemoglobin (Hb) ≥ 9 g/dL (90 g/L) (no correction therapy used within 7 days).
- •Serum creatinine ≤ 1.5 × upper limit of normal (ULN).
- •Total bilirubin (BIL) ≤ 1.5 × upper limit of normal (ULN).
- •Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) levels ≤ 2.5 × upper limit of normal (ULN); ≤ 5 × upper limit of normal (ULN) for patients with liver metastases.
- •Urinalysis is normal, or urine protein < (++), or 24-hour urine protein level < 1.0 g.
- •Normal coagulation function, with no history of active bleeding or thrombotic diseases:
- •International normalized ratio (INR) ≤ 1.5 × ULN.
- •Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
- •Prothrombin time (PT) ≤ 1.5 × ULN.
- •For patients with potential fertility, the following requirements must be met:
- •Adopt a medically acceptable contraceptive method (e.g., intrauterine device, oral contraceptives, or condoms) during the study treatment period and for 3 months after the completion of study treatment.
- •Serum human chorionic gonadotropin (β-HCG) test must be negative within 72 hours prior to study enrollment.
- •Must not be breastfeeding.
- •Patients must have provided written informed consent, and be willing and able to comply with the scheduled visits, study treatment plan, laboratory tests, and other trial procedures.
排除标准
- •History of gastrointestinal perforation and/or fistula within 6 months prior to the first dose of study medication.
- •Uncontrolled pleural, pericardial, or peritoneal effusions requiring repeated drainage.
- •Hypersensitivity to any component of monoclonal antibodies, fruquintinib, or albumin-bound paclitaxel.
- •Receipt of any of the following treatments:
- •Severe adverse reactions to prior immunotherapy.
- •Prior treatment with CTLA4 inhibitors.
- •Any study medication within 4 weeks prior to the first dose of study medication.
- •Concurrent enrollment in another clinical study (excluding observational studies or survival follow-ups of interventional studies).
- •Last dose of anti-cancer therapy ≤ 3 weeks prior to the first study medication, or fixed-field palliative radiotherapy ≤ 2 weeks prior to study intervention.
- •Corticosteroid use (>10 mg prednisone equivalent/day) within 2 weeks prior to study medication; the investigator may decide on eligibility in special cases. Inhaled/topical steroids and adrenal replacement at >10 mg/day prednisone equivalent are permitted in the absence of active autoimmune diseases.
- •Anti-tumor vaccines or live vaccines within 4 weeks prior to study medication.
- •Major surgery or severe trauma within 4 weeks prior to study medication.
- •Previous anti-tumor treatment toxicities not recovered to ≤ CTCAE Grade 1 (excluding alopecia) or the specified inclusion/exclusion criteria levels.
- •Central nervous system metastases.
- •History of active autoimmune diseases (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism) or a history of such diseases (excluding vitiligo, or childhood asthma/allergies cured and requiring no intervention in adulthood; autoimmune hypothyroidism on stable thyroid replacement; type 1 diabetes on stable insulin).
- •Immunodeficiency history (including HIV-positive status, acquired/congenital immunodeficiency, organ transplantation, or allogeneic bone marrow transplantation).
- •Inadequately controlled cardiovascular symptoms/diseases, including: (1) NYHA Class II or higher heart failure; (2) Unstable angina; (3) Myocardial infarction within 1 year; (4) Clinically significant supraventricular/ventricular arrhythmias (uncontrolled with clinical intervention).
- •Urinalysis showing urine protein ≥++ and confirmed 24-hour urine protein >1.0 g.
- •Abnormal coagulation (INR >1.5×ULN or PT >ULN+4s), with bleeding tendency or thrombolytic/anticoagulant therapy (small-dose low-molecular-weight heparin or oral aspirin for prophylaxis permitted during the trial).
- •Significant clinical bleeding or definite bleeding tendency within 3 months (e.g., gastrointestinal bleeding, hemorrhagic gastric ulcer, vasculitis). If baseline occult blood in stool is positive, re-testing is allowed; endoscopy may be performed based on clinical judgment if positive after re-testing.
- •Active ulcers, unhealed wounds, or fractures.
- •Hypertension inadequately controlled by anti-hypertensive medication (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg).
- •Severe infection (CTCAE >Grade 2) within 4 weeks prior to study medication (e.g., severe pneumonia, bacteremia, infectious complications requiring hospitalization); baseline chest imaging showing active pulmonary inflammation, or infection symptoms/signs requiring oral/IV antibiotics within 2 weeks prior to study medication (excluding prophylactic antibiotics).
- •History of interstitial lung disease (excluding radiation pneumonitis or non-infectious pneumonitis not treated with steroids).
- •Active tuberculosis (confirmed by history/CT) or history of active tuberculosis within 1 year prior to enrollment, or untreated active tuberculosis more than 1 year prior to enrollment.
- •History of any other malignant tumor within 5 years prior to study medication (excluding low-risk tumors with >90% 5-year survival rate, e.g., adequately treated basal cell/squamous cell skin cancer or cervical intraepithelial neoplasia).
- •Pregnant or breastfeeding women.
- •Other factors (e.g., concurrent severe diseases including mental illness, severely abnormal lab values, family/social factors) that may lead to forced withdrawal from the study, as determined by the investigator.
研究组 & 干预措施
Study arm
Fruquintinib Plus Nab-Paclitaxel and Iparomlimab and Tuvonralimab Injection are administered until disease progression or toxicity intolerable.
干预措施: Fruquintinib (Drug)
Study arm
Fruquintinib Plus Nab-Paclitaxel and Iparomlimab and Tuvonralimab Injection are administered until disease progression or toxicity intolerable.
干预措施: Iparomlimab and Tuvonralimab (Drug)
Study arm
Fruquintinib Plus Nab-Paclitaxel and Iparomlimab and Tuvonralimab Injection are administered until disease progression or toxicity intolerable.
干预措施: Paclitaxel (albumin-bound) (Drug)
结局指标
主要结局
Progress-free Survival(PFS)
时间窗: 24 months
The time from enrollment until tumor progression or death from any cause, whichever occurred first
次要结局
- Objective response rate (ORR)(24 months)
- Disease control rate (DCR)(24 months)
- Overall Survival (OS)(24 months)
研究者
Dai, Guanghai
Professor,Chief Physician
Chinese PLA General Hospital