NCT06904300尚未招募2 期
A Randomized, Controlled, Multi-center Phase II Study of Ivonescimab (AK112) Plus Paclitaxel Versus Paclitaxel With or Without Ramucirumab as Second-line Therapy in Subjects With Advanced Gastric or Gastroesophageal Junction（G.GEJ）Cancer Who Failed Immunochemotherapy
Sun Yat-sen University0 个研究点目标入组 110 人开始时间: 2025年8月15日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 110
- 主要终点
- PFS
研究概览
简要总结
A Randomized, Controlled, Multi-center Phase II Study of Ivonescimab (AK112) plus Paclitaxel versus Paclitaxel with or without Ramucirumab as second-line therapy in subjects with advanced gastric or gastroesophageal junction（G/GEJ）cancer who failed immunochemotherapy
详细描述
This is a randomized, controlled, multi-center Phase II trial (N ≈ 110) conducted in China to assess the safety and antitumor activity of AK112 combined with paclitaxel versus paclitaxel with or without ramucirumab in subjects with advanced gastric/gastroesophageal junction adenocarcinoma who failed immunochemotherapy. The study objective was to assess the progression-free survival (PFS) of AK112 combined with paclitaxel versus paclitaxel with or without ramucirumab in subjects with advanced gastric/gastroesophageal junction adenocarcinoma who failed immunochemotherapy. The primary endpoint was PFS assessed by RECIST v1.1, and the secondary endpoints were ORR, OS, DoR, time to response (TTR), DCR, and incidence/severity of adverse events (AEs) graded by NCI CTCAE v5.0. Eligible patients with progression after PD-1/L1 inhibitor plus platinum chemotherapy will be stratified by peritoneal metastasis (present vs. absent) and randomized 1:1 to: Group A (n=55): AK112 (20 mg/kg IV, D1/D15) + paclitaxel (80 mg/m² IV, D1/D8/D15), Q4W; Group B (n=55): Paclitaxel (80 mg/m² IV, D1/D8/D15) ± ramucirumab (8 mg/kg IV, D1/D15), Q4W. Treatment continues until disease progression, intolerable toxicity, or investigator-determined clinical futility.Tumor assessments occur every 8 weeks (±7 days) via RECIST v1.1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary written informed consent provided
- •Age ≥18 and ≤75 years, regardless of gender
- •Histologically or cytologically confirmed advanced or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma
- •Prior treatment failure with PD-1/L1 inhibitor combined with platinum-based chemotherapy; no other systemic antitumor therapy allowed (only first-line therapy permitted, with initial immunotherapy duration ≥12 weeks).Note: Patients who previously received adjuvant/neoadjuvant PD-1 inhibitor plus platinum-based chemotherapy for non-metastatic disease or curative-intent platinum chemoradiotherapy + PD-1 inhibitor for locally advanced or recurrent/metastatic disease are eligible if disease progression occurred within <6 months after the last treatment and no subsequent systemic therapy was administered.
- •ECOG performance status of 0-1
- •Life expectancy ≥3 months
- •At least one measurable lesion per RECIST v1.
- •Previously irradiated lesions may qualify as target lesions if evidence of post-radiotherapy progression exists and no alternative target lesions are available.
- •Adequate organ function:
- •Hematology (without transfusions/growth factors for 7 days): ANC ≥1.5×10⁹/L; platelets ≥100×10⁹/L; hemoglobin ≥90 g/L.
- •Liver: Total bilirubin ≤1.5×ULN; AST/ALT ≤2.5×ULN (≤5×ULN for hepatic metastases); albumin ≥28 g/L.
- •Kidney: Serum creatinine ≤1.5×ULN and CrCl ≥50 mL/min; urine protein <2+ or 24-hour urinary protein <1.0 g.
- •Coagulation: INR/PT ≤1.5×ULN (unless on anticoagulants with therapeutic ranges maintained).
- •Cardiac: LVEF ≥50%.
- •For females of childbearing potential: Negative pregnancy test within 3 days prior to treatment; highly effective contraception required during screening and for 120 days post-treatment. Postmenopausal women (amenorrhea ≥1 year) or surgically sterilized females are exempt.
- •For non-sterilized males with childbearing partners: Effective contraception during screening and for 120 days post-treatment.
- •Willingness and ability to comply with protocol-specified visits, treatments, and laboratory tests.
排除标准
- •Histologically or cytologically confirmed as other pathological types (e.g., squamous cell carcinoma, undifferentiated carcinoma, neuroendocrine carcinoma). Mixed pathological types will be categorized based on the predominant component; only subjects with >70% adenocarcinoma component confirmed by a pathologist may enroll.
- •History of other malignancies within 3 years prior to enrollment. Exceptions include malignancies cured by local therapy (e.g., basal or squamous cell skin cancer, superficial bladder cancer, in situ cervical or breast cancer).
- •Systemic anti-cancer therapy (e.g., chemotherapy, radiotherapy, immunotherapy, targeted therapy [<2 weeks for small-molecule agents], biologics) within 3 weeks prior to first dose; palliative local therapy for non-target lesions within 2 weeks.
- •Prior immunotherapy other than PD-1/PD-L1 inhibitors, including checkpoint inhibitors (anti-CTLA-4, anti-CD47, anti-SIRPα, anti-LAG-3), checkpoint agonists (ICOS, CD40, CD137, GITR, OX40), cell therapies, or biologics targeting tumor immunity.
- •Prior treatment with ramucirumab, VEGFR2 antagonists, or other VEGFR2-targeting antibodies/proteins.
- •Prior use of taxane-based agents (e.g., paclitaxel, docetaxel) in first-line systemic therapy.
- •Prior PD-1/PD-L1 inhibitor treatment with any of the following:
- •Grade ≥3 irAEs (excluding endocrine irAEs), irAEs leading to permanent discontinuation, Grade 2 immune-related cardiotoxicity, or any-grade neurological/ocular irAEs.
- •Unresolved toxicities from prior PD-1/PD-L1 therapy (not resolved to ≤Grade 1). Grade ≥2 endocrine toxicities are allowed if stable and asymptomatic under replacement therapy.
- •IrAEs requiring non-corticosteroid immunosuppressants or recurrent irAEs necessitating systemic corticosteroids.
- •Hypersensitivity to any study drug component or history of severe allergic reactions to monoclonal antibodies.
- •Bleeding diathesis or coagulation disorders.
- •Imaging showing tumor invasion of adjacent organs/vessels, necrosis, or cavitation posing risk of perforation/hemorrhage.
- •Major surgery/trauma within 30 days prior to first dose or planned surgery within 30 days post-dose; minor surgery within 3 days prior to first dose (excluding PICC/port placement).
- •Gastrointestinal risks:Esophagogastric varices, severe ulcers, unhealed wounds, perforation, fistula, abscess, or acute bleeding within 6 months; Arterial thromboembolism or Grade ≥3 venous thromboembolism (per NCI CTCAE v5.0), TIA, stroke, hypertensive crisis, or COPD exacerbation within 6 months; Uncontrolled hypertension (≥160/100 mmHg on oral therapy).
- •Cardiac history:Myocarditis, cardiomyopathy, malignant arrhythmia; Unstable angina, MI, NYHA Class ≥2 heart failure, or aortic aneurysm within 12 months; Poorly controlled arrhythmias or ischemia.
- •Active autoimmune disease requiring systemic treatment within 2 years (excluding hormone replacement).
- •Symptomatic effusions requiring diuretics or drainage (pleural, pericardial, or ascites).
- •Severe infection (hospitalization-required/sepsis) within 4 weeks; active infection requiring systemic antibiotics within 2 weeks (excluding antiviral therapy for HBV/HCV).
- •Active tuberculosis (must be ruled out if suspected) or active syphilis.
- •Organ or stem cell transplant history (excluding corneal transplants).
- •Immunodeficiency:HIV-positive; Chronic systemic corticosteroids/immunosuppressants.
- •Chronic viral hepatitis:Active HBV (HBsAg-positive with HBV DNA >500 IU/mL or >2500 copies/mL); Active HCV (allowed if cured or HCV RNA-negative).
- •Live/attenuated vaccines administered within 30 days prior to first dose or planned during the study (inactivated vaccines permitted).
- •Pregnancy, lactation.
- •History of psychiatric disorders, substance abuse, or alcoholism.
- •Other conditions deemed ineligible by the investigator.
研究组 & 干预措施
Group A
Experimental
AK112 (20 mg/kg IV, D1/D15) + paclitaxel (80 mg/m² IV, D1/D8/D15), Q4W
干预措施: AK112 + paclitaxel (Drug)
Group B
Active Comparator
Paclitaxel (80 mg/m² IV, D1/D8/D15) ± ramucirumab (8 mg/kg IV, D1/D15), Q4W
干预措施: Paclitaxel ± ramucirumab (Drug)
结局指标
主要结局
PFS
时间窗: 12-24 months
次要结局
- ORR(12-24 months)
- DCR(12-24 months)
- DoR(12-24 months)
- OS(12-24 months)
研究者
Feng Wang
Sun Yat-sen University Cancer Center
Sun Yat-sen University
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