Ivonescimab (AK112) Plus Paclitaxel as Second-line Therapy in Patients With Advanced G/GEJ Cancer

NCT06904300 | Not Yet Recruiting Phase 2

• 1 other identifier: AK112-IIT-003
• Study Type: interventional
• Target: 110
• Locations: 0 countries
• Sites: N/A

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

Conditions

Gastric (Cardia, Body) Cancer

Keywords

immunotherapy

Outcome Measures

Primary Outcomes (1)

• PFS

  12-24 months

Secondary Outcomes (4)

• ORR

  12-24 months

• DCR

  12-24 months

• DoR

  12-24 months

• OS

  12-24 months

Study Arms (2)

Group A

EXPERIMENTAL

AK112 (20 mg/kg IV, D1/D15) + paclitaxel (80 mg/m² IV, D1/D8/D15), Q4W

Drug: AK112 + paclitaxel

Group B

ACTIVE COMPARATOR

Paclitaxel (80 mg/m² IV, D1/D8/D15) ± ramucirumab (8 mg/kg IV, D1/D15), Q4W

Drug: Paclitaxel ± ramucirumab

Interventions

AK112 + paclitaxel DRUG

AK112 (20 mg/kg IV, D1/D15) + paclitaxel (80 mg/m² IV, D1/D8/D15), Q4W

Group A

Paclitaxel ± ramucirumab DRUG

Paclitaxel (80 mg/m² IV, D1/D8/D15) ± ramucirumab (8 mg/kg IV, D1/D15), Q4W

Group B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Sun Yat-sen University: lead

MeSH Terms

Conditions

Neoplasms

Interventions

Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sun Yat-sen University Cancer Center

Study Record Dates

• First Submitted: March 25, 2025
• First Posted: April 1, 2025
• Study Start: August 15, 2025
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 5, 2025

Record last verified: 2025-06