Safety and Preliminary Antitumor Activity of Ivonescimab Plus Pemetrexed and Platinum-Based Chemotherapy in Advanced Malignant Pleural Mesothelioma

NCT07885306 | Active Not Recruiting Phase 1

• 1 other identifier: 2024ZD0522805 Ia
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

This Phase 1a, open-label, dose-escalation study evaluates the safety, tolerability, and preliminary antitumor activity of ivonescimab in combination with pemetrexed and platinum-based chemotherapy as first-line treatment for advanced malignant pleural mesothelioma. Ivonescimab is evaluated at sequential dose levels of 3, 10, and 20 mg/kg using a 3+3 dose-escalation design.

Conditions

Malignant Pleural Mesothelioma, Advanced

Keywords

Ivonescimab; Pemetrexed; Platinum-Based Chemotherapy; Dose Escalation; First-Line Treatment

Outcome Measures

Primary Outcomes (1)

• Dose-Limiting Toxicities

  Incidence of protocol-defined dose-limiting toxicities.

  From the first dose through Day 28

Secondary Outcomes (5)

• Treatment-Emergent Adverse Events

  From the first dose through the last available safety assessment, up to 24 months.

• Objective Response Rate

  From the first dose through the last available tumor response assessment, up to 24 months.

• Disease Control Rate

  From the first dose through the last available tumor response assessment, up to 24 months.

• Progression-Free Survival

  From the first dose until disease progression or death from any cause, assessed up to 24 months.

• Overall Survival

  From the first dose until death from any cause, assessed up to 24 months.

Study Arms (1)

Ivonescimab Plus Pemetrexed and Platinum-Based Chemotherapy

EXPERIMENTAL

A single experimental arm consisting of sequential ivonescimab dose-escalation cohorts using a conventional 3+3 design.

Drug: Ivonescimab Combined With Chemotherapy

Interventions

Ivonescimab Combined With Chemotherapy DRUG

Ivonescimab is administered intravenously at sequential dose levels of 3, 10, and 20 mg/kg every 3 weeks (Q3W), in combination with pemetrexed 500 mg/m² and cisplatin 75 mg/m² or carboplatin AUC 5 for 4 to 6 cycles. Maintenance treatment with ivonescimab at the assigned dose with or without pemetrexed may be continued Q3W.

Ivonescimab Plus Pemetrexed and Platinum-Based Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Age 18 to 75 years.
• Histologically confirmed advanced or metastatic malignant pleural mesothelioma not amenable to surgery.
• No prior systemic anticancer therapy for advanced disease.
• ECOG PS 0-1.
• At least one measurable lesion according to modified RECIST (mRECIST).
• Adequate organ function for study treatment.
• Patients with asymptomatic or stable brain metastases are eligible.
• Able to understand the study, provide written informed consent, and comply with study procedures.

You may not qualify if:

• Active autoimmune disease requiring systemic treatment or other contraindications to immunotherapy.
• Uncontrolled hypertension, significant bleeding risk, or other contraindications to antiangiogenic therapy.
• Active interstitial lung disease or noninfectious pneumonitis.
• Active infection requiring systemic treatment.
• Other active malignancies requiring anticancer treatment.
• Severe uncontrolled medical conditions that may interfere with study treatment.
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• Ruijin Hospital: lead
• Akeso Pharmaceuticals, Inc.: collaborator

Study Sites (2)

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510120, China

Location

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants were enrolled sequentially into ivonescimab dose cohorts of 3, 10, and 20 mg/kg using a conventional 3+3 dose-escalation design.

Study Record Dates

• First Submitted: October 11, 2026
• First Posted: October 21, 2026
• Study Start: March 12, 2025
• Primary Completion: August 13, 2026
• Study Completion (Estimated): November 30, 2028
• Last Updated: October 21, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)