NCT06875076

Multicenter Single-Arm Study of Ivonescimab (AK112) Combined with Chemotherapy in Pretreated Pleural Mesothelioma

Efficacy and Safety of Ivonescimab (AK112) in Combination with Chemotherapy for the Treatment of Pretreated Pleural Mesothelioma: a Phase II Multicenter, Single-Arm Clinical Trial

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: The First Hospital of Jilin University · Academic / Other
• Sex: All
• Age: 18 Months – 75 Months
• Healthy volunteers: Not accepted

Summary

This study is a prospective, multicenter, single-arm, Phase II clinical trial evaluating the efficacy and safety of ivonescimab (AK112) combined with chemotherapy in patients with pleural mesothelioma who failed prior immunotherapy, anti-angiogenic therapy, or chemotherapy. The regimen consists of a treatment phase (ivonescimab 20mg/kg combined with pemetrexed 500mg/m²/gemcitabine 1000mg/m²/vinorelbine 25mg/m² every 21 days for 4 cycles) followed by a maintenance phase (ivonescimab monotherapy 20mg/kg every 21 days until disease progression, intolerance, or up to 2 years).The trial plans to enroll 25 patients, with the primary endpoint being objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety profiles. Exploratory endpoints investigate biomarkers such as tertiary lymphoid structures, tumor-infiltrating lymphocytes, and macrophage polarization within the tumor microenvironment.

Detailed description

Study Protocol Overview This is a prospective, multicenter, single-arm Phase II clinical trial evaluating the efficacy and safety of ivonescimab (AK112) combined with chemotherapy in pretreated pleural mesothelioma patients who failed prior immunotherapy, anti-angiogenic therapy, or chemotherapy. Utilizing a Simon two-stage design, the study plans to enroll 25 participants. The primary endpoint is objective response rate (ORR), with secondary endpoints including progression-free survival (PFS), overall survival (OS), and safety profiles. Exploratory endpoints investigate biomarkers such as tertiary lymphoid structures, tumor-infiltrating lymphocytes, and macrophage polarization in the tumor microenvironment. Treatment Regimen Treatment Phase: Ivonescimab (20mg/kg, Q3W) combined with chemotherapy (pemetrexed 500mg/m², gemcitabine 1000mg/m², or vinorelbine 25mg/m²) for 4 cycles. Maintenance Phase: Ivonescimab monotherapy (20mg/kg, Q3W) until disease progression, intolerance, or up to 2 years. Inclusion Criteria Asian ethnicity, aged 18-75, ECOG 0-1; Histologically confirmed malignant pleural mesothelioma; Progression after ≥1 and ≤2 prior systemic therapies (platinum-based chemotherapy, immunotherapy combinations, or anti-angiogenic therapy); ≥1 measurable lesion (modified RECIST 1.1); Adequate organ function (hemoglobin ≥90g/L, neutrophils ≥1.5×10⁹/L, creatinine clearance ≥50ml/min). Exclusion Criteria History of other malignancies within 5 years (except cured skin carcinoma or in situ cancer); Tumor encasing critical vasculature or with necrosis/cavitation posing bleeding risks; Active hepatitis B (untreated HBV DNA≥1000 copies/ml), HIV, or HCV infection; Active autoimmune disease requiring systemic treatment within 2 years; Participation in other interventional studies within 4 weeks prior to enrollment. Sample Size Calculation Based on Simon's two-stage design, assuming ORR improvement from 6% to 25% (α=0.05, power=80%). Stage 1 enrolls 9 patients; if ≤2 responses occur, the trial stops. Otherwise, Stage 2 proceeds, totaling 25 participants. Study Endpoints Primary: Objective response rate (ORR); Secondary: PFS, OS, disease control rate (DCR), duration of response (DoR), safety; Exploratory: Tertiary lymphoid structures (CD3/CD20/CD21), tumor-infiltrating lymphocytes (CD4/FOXP3), macrophage polarization (M1:M2).

Conditions

• Pretreated Pleural Mesothelioma

Interventions

Type	Name	Description
DRUG	Ivonescimab Combined With Chemotherapy	ivonescimab 20mg/kg combined with pemetrexed 500mg/m²/gemcitabine 1000mg/m²/vinorelbine 25mg/m² every 21 days for 4 cycles followed by a maintenance phase (ivonescimab monotherapy 20mg/kg every 21 days until disease progression, intolerance, or up to 2 years)

Timeline

• Start date: 2025-03-08
• Primary completion: 2028-01-01
• Completion: 2029-12-01
• First posted: 2025-03-13
• Last updated: 2025-03-13

Locations

1 site across 1 country: China