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Study of Iparomlimab and Tuvonralimab Plus Chemotherapy in Malignant Mesothelioma

Not Applicable
Not yet recruiting
Conditions
Malignant Mesothelioma
Mesothelioma
Interventions
Drug: iparomlimab and tuvonralimab (Dual PD-1/CTLA-4 blockade) + chemotherapy
Registration Number
NCT07131345
Lead Sponsor
National Cancer Center, China
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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
55
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Arm: Iparomlimab and Tuvonralimab Combined with Chemotherapyiparomlimab and tuvonralimab (Dual PD-1/CTLA-4 blockade) + chemotherapyPatients 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.
Primary Outcome Measures
NameTimeMethod
ORRFrom enrollment to the end of treatment at 8 weeks

Objective Response Rate,Proportion of participants achieving complete response (CR) or partial response (PR) per modified RECIST 1.1 for mesothelioma

Secondary Outcome Measures
NameTimeMethod

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