Trial Assessing Fianlimab Plus Cemiplimab Plus Chemotherapy or Cemiplimab Plus Chemotherapy in Patients With Pleural Mesothelioma

NCT07234058 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: IFCT-2402
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 37

Brief Summary

This is a multicentre, phase IIR, double non-comparative arm trial, with an initial safety run for the anti-LAG3 arm. Approximately 40 sites will participate in the study and will enroll 126 patients with treatment-naive, unresectable malignant PM. Treatment will be administered in 21-day cycles and will continue until disease progression, unacceptable toxicity, withdrawal of consent or for 2 years immunotherapy maximum. Once the patient discontinues study treatment, the treatment period will end and the patient will enter the follow-up period. No cross-over is allowed between arms.

Conditions

Pleural Mesotheliomas

Keywords

pleural mesothelioma; cemiplimab; fianlimab; anti-LAG3; anti-PD-1

Outcome Measures

Primary Outcomes (1)

• To evaluate the activity of the combination of double immunotherapy anti-LAG3+ anti-PD-1 and pemetrexed+platinum chemotherapy

  The primary endpoint is 6-month disease control rate (DCR). The analysis will be conducted in the FAS population. DCR is defined as the proportion of patients who have achieved at 6 months an overall response of CR, PR or stable disease (SD), as assessed by an independant review committee (IRC) per RECIST v1.1 modified for mesothelioma.

  6 months after randomisation.

Secondary Outcomes (8)

• Tolerance, safety of treatment

  From time of informed consent through treatment period and up to 90 days post last dose of study treatment (maximum of 2 years and 3 months).

• Progression Free Survival (PFS) as assessed by an IRC

  At progression, up to 2 years after start of treatment.

• PFS as assessed by the investigator

  At progression, up to 2 years after start of treatment.

• PFS according to the histological subtype epithelioid vs. non-epithelioid

  At progression, up to 2 years after start of treatment.

• Overall Survival (OS)

  Around 42 months.

Study Arms (2)

Arm A: cemplimab + chemotherapy

OTHER

cemplimab 350mg administered every 3 weeks for up to 24 months, with pemetrexed 500 mg/m² + platinum salt (cisplatin 75 mg/m² or carboplatin AUC 5) for 6 cycles of 21 days.

Drug: Cemiplimab; Drug: Pemetrexed (Alimta); Drug: Cisplatin; Drug: Carboplatin (AUC 5)

Arm B: cemplimab + fianlimab + chemotherapy

EXPERIMENTAL

cemplimab 350mg and fianlimab 1600mg administered every 3 weeks for up to 24 months, with pemetrexed 500 mg/m² + platinum salt (cisplatin 75 mg/m² or carboplatin AUC 5) for 6 cycles of 21 days.

Drug: Cemiplimab; Drug: Fianlimab; Drug: Pemetrexed (Alimta); Drug: Cisplatin; Drug: Carboplatin (AUC 5)

Interventions

Cisplatin DRUG

75 mg/m² every 3 weeks for 6 cycles.

Arm A: cemplimab + chemotherapy; Arm B: cemplimab + fianlimab + chemotherapy

Carboplatin (AUC 5) DRUG

AUC 5 (recommended maximum dose of 800 mg) every 3 weeks for 6 cycles.

Arm A: cemplimab + chemotherapy; Arm B: cemplimab + fianlimab + chemotherapy

Cemiplimab DRUG

350mg every 3 weeks for up to 24 months.

Also known as: Libtayo

Arm A: cemplimab + chemotherapy; Arm B: cemplimab + fianlimab + chemotherapy

Fianlimab DRUG

1600mg every 3 weeks for up to 24 months.

Arm B: cemplimab + fianlimab + chemotherapy

Pemetrexed (Alimta) DRUG

500 mg/m² every 3 weeks for 6 cycles.

Also known as: Alimta

Arm A: cemplimab + chemotherapy; Arm B: cemplimab + fianlimab + 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:

• Signed written Informed Consent.
• Subjects must have signed and dated an IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
• Histological diagnosis (no cytology allowed, thoracoscopy biopsy recommended).
• Non resectable PM as evaluated by a specialist MTB comprising a specialized thoracic surgeon.
• Measurable disease by CT with iodure injection according to RECIST 1.1 modified criteria for mesothelioma (pleural thickness perpendicular to the chest wall or mediastinum of 7 mm or more, on 2 positions, at 3 separate levels on transverse cuts of CT-scan, at least 1 cm apart, the sum of 6 measurements defining a pleural unidimensional measure), or according to RECIST1.1 criteria for mediastinal nodes or metastatic lesion.
• ECOG PS 0 and 1.
• Weight loss \<10% within 3 months of study entry.
• Chemo-naive and immuno-naive.
• Age ≥18 years, \<76 years.
• Life expectancy \>3 months.
• Available pathological samples (at least 10 slides from the thoracoscopy pleural biopsy sample).
• Adequate biological functions: creatinine clearance ≥45 mL/min (Cockroft or MDRD or CKD-epi); neutrophils ≥1500/mm3; platelets ≥100 000/mm3; haemoglobin ≥9g/dL; AST and ALT \<3 x ULN, total bilirubin \<2 x ULN (patients with hepatic metastases or Gilbert's syndrome must have AST and ALT ≤5 x ULN and a baseline total bilirubin ≤2 x ULN).
• WOCBP\* must have a negative serum (beta-hCG) at screening.
• \*WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the CTFG guidance. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

You may not qualify if:

• ECOG PS\>2.
• Previous cancer treatment including chemotherapy or immunotherapy with anti-PD-1, anti-PD-L1, Anti-CTLA4 or any ICI antibody.
• Pleural effusion as the only radiological abnormality without measurable pleural thickness or mediastinal node enlargement.
• Peritoneal, pericardial or tunica vaginalis testis mesothelioma.
• Previous diagnosis of adenocarcinoma from any anatomic site within the previous 5 years, with the exception of prostate adenocarcinoma history within the previous 5 years, in case of localized prostate cancer, with good prognostic factors according to d'Amico classification (\<T2a, score de Gleason ≤6 and PSA ≤10 ng/ml) provided they were treated in a curative way (surgery or radiotherapy, without any chemotherapy). Previous or active cancer within the previous 5 years (except for treated carcinoma in situ of the cervix, or basal cell skin cancer treated or not).
• Uncontrolled pleural effusion requiring frequent thoracocentesis (needing thoracoscopic pleural pleurodesis before possible accrual).
• Symptomatic untreated brain metastasis (without previous whole brain radiotherapy or stereotactic ablative brain radiotherapy or without surgical resection). At least 2 weeks delay between the end of radiotherapy and the beginning of immuno-chemotherapy treatment should be respected. Asymptomatic brain metastasis, not needing corticosteroids greater than 10 mg prednisone equivalent daily or mannitol infusions, are allowed.
• Radiotherapy needed at initiation of tumour treatment, except bone palliative radiotherapy on a painful or compressive metastasis, or radiotherapy on thoracic drain or puncture routes.
• History of previous primary immunodeficiency, organ transplantation needing an immunosuppressive treatment, any immunosuppressive drug within 28 days before randomisation date, or history of severe toxicity (grade 3/4) by immune mechanism linked to another immunotherapy treatment for any kind of disease.
• Systemic treatment with corticosteroids with greater dose than 10 mg prednisone equivalent daily, within 14 days before initiation of the treatment. Inhaled, nasal or topic corticosteroids are allowed.
• History of active autoimmune disease, needing systemic immunosuppressive drug, including but not limited to rheumatoid polyarthritis, myasthenia, autoimmune hepatitis, systemic Lupus, Wegener's granulomatosis, vascular thrombosis associated with anti-phospholipid syndrome, Sjogren's syndrome with interstitial pulmonary disease, recent Guillain-Barré syndrome within previous 15 years, multiple sclerosis, vasculitis, or glomerulonephritis.
• Patients with type I diabetes, or hypothyroidy, or immune cutaneous disease (vitiligo, psoriasis, alopecia) or benign rheumatoid polyarthritis not needing any immunosuppressive systemic treatment or over 10 mg daily oral steroids, or benign sicca syndrome (Sjogren) without interstitial pulmonary disease, or history of past Guillain-Barré syndrome beyond 15 previous years, totally reversible with no sequalae, no systemic immunosuppressive treatment during the last 20 years, can be included. Patients with Grave's disease or psoriasis not requiring systemic therapy within the last two years from randomisation can be included.
• Active inflammatory intestinal disease (diverticulosis, Crohn disease, haemorrhagic recto-colitis, coeliac disease) requiring systemic treatment, or any serious chronic intestinal disease with uncontrolled diarrhoea.
• History or current evidence of significant (CTCAE grade ≥2) local or systemic infection (e.g. cellulitis, pneumonia, septicaemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.
• Active uncontrolled infection requiring therapy including active tuberculosis. Past primary pulmonary tuberculosis in youth does not consist of a contra-indication. Past tuberculosis disease history does not consist of a contra-indication provided the patient was treated during at least 6 months by anti-tuberculosis antibiotic treatment.

Sponsors & Collaborators

• Intergroupe Francophone de Cancerologie Thoracique: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (37)

Aix-Pertuis - CHI

Aix-en-Provence, France

Location

Amiens - CHU

Amiens, France

Location

Angers - CHU

Angers, France

Location

Avignon - CH

Avignon, France

Location

Besançon - CHU

Besançon, 75009, France

Location

Bordeaux - Institut Bergonié

Bordeaux, France

Location

Boulogne - APHP Ambroise Paré

Boulogne-Billancourt, France

Location

Caen - CHU

Caen, France

Location

Clermont-Ferrand - Centre Jean Perrin

Clermont-Ferrand, France

Location

Clermont-Ferrand - CHU

Clermont-Ferrand, France

Location

Créteil - CHI

Créteil, France

Location

Dijon - Centre Georges-François Leclerc

Dijon, France

Location

Grenoble - CHU

Grenoble, France

Location

La Roche-Sur-Yon - CHD Vendée

La Roche-sur-Yon, France

Location

Le Mans - CHG

Le Mans, France

Location

Lille - CHU

Lille, France

Location

Marseille - APHM Nord

Marseille, France

Location

Marseille - Hôpital Européen

Marseille, France

Location

Montpellier - CHU

Montpellier, France

Location

Mulhouse - GHRMSA

Mulhouse, France

Location

Nantes - Hôpital Laennec

Nantes, France

Location

Paris - APHP Bichat

Paris, France

Location

Paris - APHP Cochin

Paris, France

Location

Bordeaux - CHU

Pessac, France

Location

Lyon - HCL

Pierre-Bénite, France

Location

Reims - Institut Godinot

Reims, France

Location

Rennes - CHU

Rennes, France

Location

Nantes - Institut de Cancérologie de l'Ouest

Saint-Herblain, 75009, France

Location

Saint-Nazaire - Clinique Mutualiste de l'Estuaire

Saint-Nazaire, France

Location

Strasbourg - Nouvel Hôpital Civil

Strasbourg, 75009, France

Location

Toulon - CHI

Toulon, France

Location

Toulon - Sainte Anne HIA

Toulon, France

Location

Toulouse - CHU

Toulouse, France

Location

Tours - CHU

Tours, 75009, France

Location

Vandoeuvre-lès-Nancy - Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

Location

Villefranche sur Saône - CH

Villefranche-sur-Saône, France

Location

Villejuif - Gustave Roussy

Villejuif, France

Location

Related Links

• IFCT website

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

cemiplimab; Pemetrexed; Cisplatin; Carboplatin

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)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Dr Myriam LOCATELLI-SANCHEZ

  Hôpital Lyon-Sud, Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

• Pr Gérard ZALCMAN

  Hôpital Bichat, AP-HP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Contact IFCT

CONTACT

+33 156811046; contact@ifct.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The parallel arms are not comparative.

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 18, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): September 1, 2029
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

FR (37)