Induction Chemo+Immunotherapy in Resectable Epithelioid and Biphasic Pleural Mesothelioma (CHIMERA Study)

NCT06155279 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: IOV-Me-01-2023-CHIMERA
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 8

Brief Summary

This is a prospective, open-label, multi-site Phase II trial of pembrolizumab in combination with pemetrexed and cisplatin or carboplatin as neo-adjuvant therapy followed by surgery and adjuvant pembrolizumab in patients affected by resectable stage I-IIIa chemonaïve epithelioid/biphasic pleural mesothelioma.

Conditions

Pleural Mesothelioma

Outcome Measures

Primary Outcomes (1)

• Primary endpoint - To evaluate the activity of neo-adjuvant treatment by the determination of pathological complete response rate (pCR)

  Pathological complete response defined as 0% residual viable tumor cells in the primary tumor and in sampled lymph nodes, following neoadjuvant treatment as assessed by central pathology assessment. Patients who are not evaluable per central pathology assessment (this includes patients with R2 margins) or who do not have a surgical specimen will be considered as non-pCR (eg, pathology assessments captured as "non-evaluable" or "missing," as appropriate). Patients who received less than 2 cycles out of the planned 3 cycles of neoadjuvant therapy due to unacceptable toxicity will not be considered in the pCR evaluation.

  Pathological complete response will be evaluated following neoadjuvant treatment and within 6 weeks after the last dose of study intervention.

Secondary Outcomes (6)

• Secondary endpoint - To further evaluate the activity of neo-adjuvant treatment in terms of major pathological response.

  Major pathological response will be evaluated at the time of surgery that will be performed within 6 weeks after the last dose of study intervention.

• Secondary endpoint - To further evaluate the activity of neo-adjuvant treatment in terms of overall response rate (ORR).

  The ORR will be evaluated: at the time of the screening (within 4 weeks before the neoadjuvant treatment); within 6 weeks after neoadjuvant treatment; within 10 weeks after surgery; at every radiological assessment with CT-scan up to 24 months

• Secondary endpoint - To evaluate the efficacy of neo-adjuvant treatment in terms of overall survival (OS).

  From the start of treatment to death from any cause, up to 24 months.

• Secondary endpoint - To evaluate the efficacy of neo-adjuvant treatment in terms of event free survival (EFS).

  From the start of treatment to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause, up to 24 months.

• Secondary endpoint - To evaluate the feasibility of neo-adjuvant treatment in terms of resection rate and rate of patients who complete all cycles of neoadjuvant treatment and following surgery.

  From the screening to the surgery which is performed within 6 weeks after the neoadjuvant treatment, up to 22 weeks.

Study Arms (1)

Single arm

EXPERIMENTAL

Single arm Carboplatin/Cisplatin - Pemetrexed - Pembrolizumab The neoadjuvant systemic treatment will be based on three cycles of pembrolizumab 200 mg flat dose in combination with standard doses of cisplatin (75 mg/sm) or carboplatin (AUC 5) and pemetrexed (500 mg/sm) administered intra-venous every 3 weeks. The surgical intervention of pleurectomy/decortication will be planned to occur within 6 weeks after the completion of neoadjuvant treatment. The adjuvant systemic treatment will be based on 14 cycles of pembrolizumab 200 mg flat dose administered intra-venous every 3 weeks. Patients should be able to start pembrolizumab following surgery as soon as clinically feasible and within 10 weeks from surgery.

Drug: Carboplatin/Cisplatin - Pemetrexed - Pembrolizumab

Interventions

Carboplatin/Cisplatin - Pemetrexed - Pembrolizumab DRUG

The neoadjuvant systemic treatment will be based on three cycles of pembrolizumab 200 mg flat dose in combination with standard doses of cisplatin (75 mg/sm) or carboplatin (AUC 5) and pemetrexed (500 mg/sm) administered intra-venous every 3 weeks. The surgical intervention of pleurectomy/decortication will be planned to occur within 6 weeks after the completion of neoadjuvant treatment. The adjuvant systemic treatment will be based on 14 cycles of pembrolizumab 200 mg flat dose administered intra-venous every 3 weeks. Patients should be able to start pembrolizumab following surgery as soon as clinically feasible and within 10 weeks from surgery.

Also known as: Keytruda

Single arm

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of surgical resectable stage I-IIIA treatment-naïve epithelioid/biphasic pleural mesothelioma will be enrolled in this study.
• Diagnosis of epithelioid/biphasic pleural mesothelioma must be histologically confirmed, preferably by video-assisted thoracoscopic surgery (VATS).
• At screening, complete surgical resection of the mesothelioma must be deemed achievable, as assessed by a multidisciplinary evaluation.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Histologically proved diagnosis of treatment-naive epithelioid/biphasic pleural mesothelioma.
• Surgical resectable disease \[stage I - II - IIIA (T1-3 - N0/1-M0) according to ninth TNM edition\].
• No previous surgical resection of mesothelioma.
• Archival tumor tissue sample or newly obtained \[core, incisional or excisional\] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Has adequate PFT defined as an FEV1 \>50% (of predicted normal volume) or ≥ 1.2 L/Sec and a DLCO \>40% of predicted normal value. Participants for whom DLCO measurements are not available will be deemed to have adequate oxygen transfer if pulse oximetry (O2 saturation) ≥90% room air.
• Have adequate organ function as defined in the following table (Table 3). Specimens must be collected within 10 days prior to the start of study intervention.

You may not qualify if:

• Subject incapacitated to understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
• Primitive peritoneal, pericardial and tunica vaginalis testis mesotheliomas.
• Cytological diagnosis of pleural mesothelioma not histologically confirmed.
• Prior treatment with systemic anti-cancer therapy for pleural mesothelioma, prior intraoperative intracavitary chemotherapy for pleural mesothelioma, prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
• Has uncontrolled, potentially reversible cardiac conditions, as Investigator's judgment (eg. Unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \> 500 millisecond) or participants with congenital long QT syndrome.
• Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
• Known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or adequately treated carcinoma in-situ without evidence of disease are not excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid).
• History of Hepatitis B (defined as HbsAg reactive) or known active Hepatitis C virus (defined as detectable HCV RNA \[qualitative\]) infection.
• Has not adequately recovered from major surgery or has ongoing surgical complications.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• Istituto Oncologico Veneto IRCCS: lead
• MSD Italia S.r.l.: collaborator

Study Sites (8)

Humanitas Gavazzeni

Bergamo, Italia/Bergamo, 24125, Italy

Location

IFO - Istituto Tumori Regina Elena, Roma

Roma, Italia/Roma, 00144, Italy

Location

Istituto Clinico Humanitas

Rozzano, Milano, 20089, Italy

Location

Centro di Riferimento Oncologico (CRO) IRCCS

Aviano, Pordenone, Italy

Location

Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo

Alessandria, Italy

Location

Azienda Ospedaliero-Universitaria S. Anna

Ferrara, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

Location

Azienda Ospedaliera-Universitaria di Parma

Parma, Italy

Location

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Carboplatin; pembrolizumab

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)

Coordination Complexes; Organic Chemicals

Study Officials

• Giulia Pasello, MD

  Istituto Oncologico Veneto IOV IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: The neoadjuvant systemic treatment will be based on three cycles of pembrolizumab 200 mg flat dose in combination with standard doses of cisplatin (75 mg/sm) or carboplatin (AUC 5) and pemetrexed (500 mg/sm) administered intra-venous every 3 weeks. The surgical intervention of pleurectomy/decortication will be planned to occur within 6 weeks after the completion of neoadjuvant treatment. The adjuvant systemic treatment will be based on 14 cycles of pembrolizumab 200 mg flat dose administered intra-venous every 3 weeks. Patients should be able to start pembrolizumab following surgery as soon as clinically feasible and within 10 weeks from surgery.

Study Record Dates

• First Submitted: November 22, 2023
• First Posted: December 4, 2023
• Study Start: November 6, 2024
• Primary Completion: December 22, 2025
• Study Completion (Estimated): March 1, 2027
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (8)