Status:
NOT_YET_RECRUITING
Ivonescimab (AK112) Plus Paclitaxel as Second-line Therapy in Patients With Advanced G/GEJ Cancer
Lead Sponsor:
Sun Yat-sen University
Conditions:
Gastric (Cardia, Body) Cancer
Eligibility:
All Genders
18-75 years
Phase:
PHASE2
Brief Summary
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 g...
Detailed Description
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 witho...
Eligibility Criteria
Inclusion
- 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 v1.1. 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.
Exclusion
- 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.
Key Trial Info
Start Date :
August 15 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2028
Estimated Enrollment :
110 Patients enrolled
Trial Details
Trial ID
NCT06904300
Start Date
August 15 2025
End Date
December 31 2028
Last Update
June 5 2025
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