Study of Pembrolizumab Plus Chemotherapy With Lenvatinib for Malignant Pleural Mesothelioma

NCT06318286 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MK3475-IIT-60977
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

In this Phase-II study, the investigators will investigate the efficacy and safety of lenvatinib in combination with pembrolizumab and chemotherapy in patients with malignant pleural mesothelioma.

Conditions

Malignant Pleural Mesothelioma

Keywords

Pembrolizumab; Lenvatinib

Outcome Measures

Primary Outcomes (1)

• Tumor shrinkage (response rate) (Physician Judgment by Medical Institution, Modified RECIST [Response Evaluation Criteria in Solid Tumors] criteria)

  The overall response and the best overall response are the result of the diagnostic imaging evaluated based on Modified RECIST criteria, and the result of the diagnostic imaging does not include clinical progression. The diagnostic imaging for which the overall response is determined other than inevaluable (NE) are considered as the evaluable diagnostic imaging. The response rate is defined as the proportion of participants who have complete response (CR) or partial response (PR).

  2 years

Secondary Outcomes (6)

• Progression-Free survival (PFS) (Physician Judgment by Medical Institution, Modified RECIST criteria)

  2 years

• Overall survival time (OS)

  2 years

• Tumor shrinkage (disease control rate) (Physician Judgment by Medical Institution, Modified RECIST criteria)

  2 years

• Duration of response (Physician Judgment by Medical Institution, Modified RECIST criteria)

  2 years

• Best overall response (Physician Judgment by Medical Institution, Modified RECIST criteria)

  2 years

Study Arms (1)

Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab

EXPERIMENTAL

In induction treatment, study interventions include oral lenvatinib, 8 mg quaque die (QD), and pembrolizumab, 200 mg, carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m2), and pemetrexed, 500 mg/m2 all given by intravenous (IV) infusion on Day 1 of a 21-day cycle. Lenvatinib, pembrolizumab, carboplatin/cisplatin, and pemetrexed combination treatment will be given for 4-6 cycles, after which participants may receive maintenance treatment with Lenvatinib, 20 mg QD, and pembrolizumab, 200 mg. Lenvatinib and Pembrolizumab may be given for up to a total of 35 cycles.

Drug: Lenvatinib; Drug: Pemetrexed; Drug: Cisplatin/Carboplatin; Drug: Pembrolizumab

Interventions

Lenvatinib DRUG

Induction treatment: lenvatinib, 8 mg QD on Day 1 of a 21-day cycle for 4-6 cycles. Maintenance treatment: Lenvatinib, 20 mg QD may be given for up to a total of 35 cycles.

Also known as: E7080

Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab

Pemetrexed DRUG

Pemetrexed, 500 mg/m2 will be given by intravenous (IV) infusion on Day 1 of a 21-day cycle for 4-6 cycles.

Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab

Cisplatin/Carboplatin DRUG

Carboplatin (AUC 5 mg/mL/min) or Cisplatin (75 mg/m2) will be given by IV infusion on Day 1 of a 21-day cycle for 4-6 cycles.

Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab, 200 mg will be given by IV infusion on Day 1 of a 21-day cycle for up to a total of 35 cycles.

Also known as: MK-3475

Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Patients with unresectable advanced or metastatic malignant pleural mesothelioma without prior treatment for malignant pleural mesothelioma
• Patients expected to survive more than 90 days
• Patients with a transcutaneous oxygen saturation of 94% or greater measured with a pulse oximeter at rest without oxygen inhalation within 7 days prior to enrollment
• Patients who have given written consent to participate in this clinical trial (consent by a surrogate is also acceptable, if applicable).
• Patients who are judged by the principal investigator or coinvestigator to have one or more measurable lesions as defined in Modified RECIST by CT or MRI imaging within 28 days prior to enrollment. However, if the measurable lesion is a pleural lesion only and there is a history of pleurodesis (patients who underwent pleurodesis within 14 days prior to enrollment or pleurodesis with Picibanil within 28 days prior to enrollment are excluded), only patients whose measurable lesion was confirmed on imaging after pleurodesis are eligible.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of malignant pleural mesothelioma will be enrolled in this study.
• Have adequate organ function as defined in the following table. All clinical laboratory tests in the screening period should be performed within 10 days prior to the start of study intervention.

You may not qualify if:

• Patients with concomitant or pre-existing severe hypersensitivity reactions to other drugs, including antibody preparations
• A women of childbearing potential who has a positive urine pregnancy test within 72 hours prior to trial registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• Has received prior therapy with an anti-PD-1 (anti-programmed cell death protein 1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to trial registration.
• Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible Note: If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• 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.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
• Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• 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 (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

Sponsors & Collaborators

• Hyogo Medical University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Hyogo Medical University Hospital

Nishinomiya, Hyōgo, 6638501, Japan

RECRUITING

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

lenvatinib; Pemetrexed; Cisplatin; 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)

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

• Kozo Kuribayashi, MD, PhD

  Department of Respiratory Medicine and Hematology, Hyogo Medical University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kozo Kuribayashi, MD, PhD

CONTACT

+81-798-45-6596; kuririn@hyo-med.ac.jp

Tetsuya Takagawa, MD, PhD

CONTACT

+81-798-45-6265; takagawa@hyo-med.ac.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a single-arm, open-label study to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab and chemotherapy in patients with malignant pleural mesothelioma. Patients 18 years of age or older will be eligible for enrollment if they had histologically confirmed unresectable malignant pleural mesothelioma.

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: March 19, 2024
• Study Start: March 13, 2024
• Primary Completion: April 30, 2026
• Study Completion (Estimated): October 30, 2026
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)