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
Overview
- Phase
- Phase 2
- Intervention
- AK112 + paclitaxel
- Conditions
- Not specified
- Sponsor
- Sun Yat-sen University
- Enrollment
- 110
- Primary Endpoint
- PFS
- Status
- Not yet recruiting
- Last Updated
- 11 months ago
Overview
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 gastroesophageal junction（G/GEJ）cancer who failed immunochemotherapy
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 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.
Investigators
Feng Wang
Sun Yat-sen University Cancer Center
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Group A
AK112 (20 mg/kg IV, D1/D15) + paclitaxel (80 mg/m² IV, D1/D8/D15), Q4W
Intervention: AK112 + paclitaxel
Group B
Paclitaxel (80 mg/m² IV, D1/D8/D15) ± ramucirumab (8 mg/kg IV, D1/D15), Q4W
Intervention: Paclitaxel ± ramucirumab
Outcomes
Primary Outcomes
PFS
Time Frame: 12-24 months
Secondary Outcomes
- ORR(12-24 months)
- DCR(12-24 months)
- DoR(12-24 months)
- OS(12-24 months)