Study of Iparomlimab and Tuvonralimab Plus Chemotherapy in Malignant Mesothelioma

NCT ID: NCT07131345

Last Updated: 2025-08-20

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2027-07-01

Brief Summary

This clinical trial aims to investigate the effectiveness and safety of a new treatment combination-Iparomlimab and Tuvonralimab (QL1706, a dual-function antibody targeting PD-1 and CTLA-4) combined with chemotherapy-for patients with malignant mesothelioma (MM). MM is a rare and aggressive cancer often linked to asbestos exposure. Current treatments have limited success, and this study seeks to explore a potentially more effective and safer option.

Study Design:

Phase Ib (Safety Phase): 6 patients will receive the combination therapy to assess safety. If no major safety issues arise, the study will proceed to Phase II.

Phase II (Efficacy Phase): 49 patients will be enrolled to evaluate treatment effectiveness. The study includes two groups for first-line treatment and second-line treatment.

Detailed Description

Study Rationale Malignant mesothelioma (MM) is a rare and aggressive cancer primarily associated with asbestos exposure. Despite advances in treatment, the prognosis remains poor, with a median overall survival (OS) of approximately 12-18 months for advanced disease. Current standard therapies include platinum-based chemotherapy combined with pemetrexed, immune checkpoint inhibitors (ICIs) such as nivolumab plus ipilimumab, or pembrolizumab with chemotherapy. However, these treatments have limitations, including significant toxicity (e.g., immune-related adverse events, irAEs) and modest survival benefits in certain populations.

The iparomlimab and tuvonralimab (QL1706) combination is a novel bispecific antibody therapy targeting PD-1 and CTLA-4, designed to enhance anti-tumor immune responses while minimizing toxicity. Preclinical and early clinical data suggest this dual checkpoint blockade may offer comparable efficacy to existing ICI combinations but with an improved safety profile. Given the unmet need for effective and tolerable therapies in MM, this study evaluates the clinical potential of iparomlimab and tuvonralimab combined with chemotherapy in Chinese patients.

Study Design

This is a single-arm, multicenter, open-label Ib/II trial with two sequential phases:

Phase Ib (Safety Run-In, n=6):

Evaluates the safety of iparomlimab and tuvonralimab + chemotherapy in patients with 1-3 prior lines of therapy.

Phase II (Expansion, n=49):

First-line cohort (n=39): Patients receive iparomlimab and tuvonralimab + pemetrexed/platinum (Simon two-stage design).

Second-line cohort (n=10): Fixed-sample evaluation of iparomlimab and tuvonralimab + investigator-selected chemotherapy.

Treatment Regimen

Induction Phase (4-6 cycles, Q3W):

Iparomlimab and tuvonralimab (5 mg/kg IV, Day 1)

Chemotherapy backbone:

First-line: Pemetrexed (500 mg/m²) + cisplatin (75 mg/m²) or carboplatin (AUC 5).

Second-line: Investigator's choice (pemetrexed, gemcitabine, or vinorelbine).

Maintenance Phase (up to 2 years, Q3W):

Iparomlimab and tuvonralimab monotherapy (5 mg/kg) until progression or unacceptable toxicity.

Conditions

Malignant Mesothelioma; Mesothelioma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm: Iparomlimab and Tuvonralimab Combined with Chemotherapy

Patients will receive Iparomlimab and Tuvonralimab (5 mg/kg) plus chemotherapy (pemetrexed and platinum drugs) every 3 weeks for 4-6 cycles, followed by maintenance therapy with Iparomlimab and Tuvonralimab for up to 2 years.

Group Type: EXPERIMENTAL

iparomlimab and tuvonralimab (Dual PD-1/CTLA-4 blockade) + chemotherapy

Intervention Type: DRUG

Novel Bispecific Checkpoint Inhibition:

QL1706(iparomlimab and Tuvonralimab) was generated by using MabPair, a new technological platform that enables the production of two antibodies close to their natural forms from a single host cell line and is manufactured as one product. QL1706 contains a mixture of anti-PD-1 IgG4 and anti-CTLA-4 IgG1 that were produced together in a fixed ratio. Each antibody was individually optimized to achieve desirable target coverage and antibody effector functions.

Chemotherapy for first-line treatment (pemetrexed plus cisplatin or carboplatin )

Chemotherapy for second-line treatment (pemetrexed, gemcitabine or vinorelbine)

Interventions

iparomlimab and tuvonralimab (Dual PD-1/CTLA-4 blockade) + chemotherapy

Novel Bispecific Checkpoint Inhibition:

QL1706(iparomlimab and Tuvonralimab) was generated by using MabPair, a new technological platform that enables the production of two antibodies close to their natural forms from a single host cell line and is manufactured as one product. QL1706 contains a mixture of anti-PD-1 IgG4 and anti-CTLA-4 IgG1 that were produced together in a fixed ratio. Each antibody was individually optimized to achieve desirable target coverage and antibody effector functions.

Chemotherapy for first-line treatment (pemetrexed plus cisplatin or carboplatin )

Chemotherapy for second-line treatment (pemetrexed, gemcitabine or vinorelbine)

Intervention Type: DRUG

Other Intervention Names

QL1706+chemotherapy

Eligibility Criteria

Inclusion Criteria

• Subjects must provide informed consent prior to initiating any study-specific procedures.
• Male or female subjects aged ≥18 and ≤75 years.
• Histologically/cytologically confirmed malignant mesothelioma (MM), including malignant pleural mesothelioma (PM) and malignant peritoneal mesothelioma (PeM).
• Subjects with MM unsuitable for radical resection and/or radiotherapy per AJCC 8th Edition.
• Subjects who received neoadjuvant/adjuvant chemotherapy for radical surgery completed >6 months prior to current recurrent disease diagnosis, not counted in subsequent treatment lines.
• Prior systemic anti-tumor therapy requirements:

• Safety run-in phase: ≥1 prior anti-tumor therapy line (maximum 3 lines)
• Phase II first-line cohort: No prior systemic anti-tumor therapy
• Phase II second-line cohort: Only 1 prior systemic anti-tumor therapy line
• ECOG performance status 0-2.
• Investigator-assessed life expectancy >3 months.
• Adequate hematological parameters.

Exclusion Criteria

• Prior CTLA-4 inhibitors prohibited; prior PD-1/PD-L1 allowed unless discontinued for immune toxicity
• Immunomodulators within 14 days (e.g., thymosin, interleukin-2, interferon)
• Significant cardiovascular history within 6 months

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Qilu Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Affiliated Cancer Hospital of Zhengzhou University

UNKNOWN

Sponsor Role: collaborator

Beijing Chest Hospital, Capital Medical University

OTHER

Sponsor Role: collaborator

The Affiliated Hospital of Inner Mongolia Medical University

OTHER

Sponsor Role: collaborator

Shaanxi Provincial Cancer Hospital

OTHER

Sponsor Role: collaborator

National Cancer Center, China

OTHER

Sponsor Role: lead

Responsible Party

Puyuan Xing

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Puyuan Xing, MD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Center, China

Central Contacts

Puyuan Xing, MD

Role: CONTACT

xingpuyuan@cicams.ac.cn

8618611417207

Other Identifiers

NCC5281

Identifier Type: -

Identifier Source: org_study_id