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Malignant Pleural MesotheliomaPhase 2PENINSULANCT06318286

Study of Pembrolizumab Plus Chemotherapy With Lenvatinib for Malignant Pleural Mesothelioma

A Phase 2 study testing Lenvatinib, Pemetrexed and Cisplatin/Carboplatin in people with Malignant Pleural Mesothelioma, run by Hyogo Medical University at 1 site in Japan.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Pleural Mesothelioma
What is being tested?
Lenvatinib, Pemetrexed and Cisplatin/Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteJapan
Study dates
13 Mar 2024to 30 Oct 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.
  • Has an active infection requiring systemic therapy.
  • Has a known history of Human Immunodeficiency Virus (HIV) infection.
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]reactive or HBV-DNA detected) or known active Hepatitis C virus (defined as HCV RNA [qualitative] detected or HCV antibody reactive, if HCV-RNA is not the local SOC) infection.
  • 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.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
  • Has had an allogenic tissue/solid organ transplant.
  • Patients with diverticulitis or symptomatic gastrointestinal ulcer disease
  • Patients with pleural effusions requiring drainage more frequently than once every 2 weeks
  • Patients with pericardial or ascites effusions requiring treatment
  • Patients with uncontrolled tumor-related pain
  • Patients with a history of transient ischemic attack, cerebral vascular attack, thrombosis or thromboembolism (pulmonary artery embolism or deep vein thrombosis) within 180 days prior to registration Patients with the following unmanageable or serious cardiovascular diseases
  • Myocardial infarction within 180 days prior to enrollment
  • Uncontrolled angina pectoris within 180 days prior to enrollment
  • New York Heart Association（NYHA）Classification of Cardiac Function Classification III or IV congestive heart failure
  • Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg for >24 hours) despite appropriate therapy
  • Uncontrolled arrhythmia
  • Patients receiving anticoagulation therapy (excluding antiplatelet therapy including low-dose aspirin) or with diseases requiring such therapy
  • Patients with uncontrolled diabetes mellitus
  • Patients undergoing surgical treatment with local or surface anesthesia within 14 days prior to enrollment
  • Patients undergoing surgical treatment involving general anesthesia within 28 days prior to enrollment
  • Patients who underwent pleurodesis within 14 days prior to enrollment
  • Patients who underwent pleurodesis with picibanil within 28 days prior to enrollment
  • Patients who underwent pericardial adhesion within 28 days prior to enrollment
  • Patients who underwent peritoneal adhesions
  • Patients who received radiation therapy for pain relief within 14 days prior to enrollment
  • Patients who have received radiopharmaceuticals (excluding the use of radiopharmaceuticals for laboratory and diagnostic purposes) within 56 days prior to enrollment
  • Patients who have received other unapproved drugs (including approved drugs not indicated for malignant pleural mesothelioma, drugs administered through clinical studies or unapproved combination drugs, or new formulations) within 28 days (90 days for antibody products) prior to enrollment
  • Patients with prolonged QT interval (QTc, corrected by Fridericia's formula) > 480 msec
  • Participants with proteinuria >1+ on urine dipstick testing/urinalysis will undergo24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ≥1 g/24 hours will be ineligible.
  • Active hemoptysis (bright red blood ≥ 1/2 teaspoon) or other uncontrolled bleeding within 14 days prior to the study registration.
  • Radiographic evidence of intratumoral cavitations, encasement, or invasion of a major blood vessel. Additionally, the degree of proximity to major blood vessels should be considered because for exclusion because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy. (In the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta).

Trial locations and contacts

1 site in 1 country.

Japan1 site

  • Hyogo Medical University Hospital

    Nishinomiya, Hyōgo, 6638501

Other trials in Japan

About this study

Official title: First-line Pembrolizumab Plus Platinum Doublet Chemotherapy With Lenvatinib in Unresectable Malignant Pleural Mesothelioma：Multi-Institutional, Single-Arm Phase 2 Trial

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.

Read the detailed description

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. The study will consist of a screening phase, a treatment phase, and a follow-up phase. Patients who meet the Inclusion Criteria, do not meet the Exclusion Criteria, and are judged by the investigator to be eligible for this clinical trial will be included. Subjects who meet all of the criteria listed in Criteria for Administration of Investigational Drugs may continue to receive the investigational drug. If a subject receiving investigational drugs meets any of the criteria listed in Discontinuation Criteria of Investigational Drugs, the subject will be evaluated at the end of the treatment phase (at the time of discontinuation) and moved to the post-observation phase.

Being tested
Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, Pembrolizumab
Keywords
Pembrolizumab, Lenvatinib
Medical subject headings
Mesothelioma, Malignant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LenvatinibDrug

    Also called E7080

    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.

  • PemetrexedDrug

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

  • Cisplatin/CarboplatinDrug

    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.

  • PembrolizumabDrug

    Also called MK-3475

    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.

Study groups in NCT06318286
Study groupRoleWhat they receive
Lenvatinib, Pemetrexed, Cisplatin/Carboplatin, and PembrolizumabExperimentalIn 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.
Receives: Drug: Lenvatinib; Drug: Pemetrexed; Drug: Cisplatin/Carboplatin; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 2 years

Secondary outcomes (6)

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

    Progression-Free survival (PFS) is defined as the time from the date of treatment start to the date of the first documentation of progressive disease (PD), as determined by the overall response of Modified RECIST criteria, or death from any cause, whichever is earlier.

    Measured: 2 years

  2. Overall survival time (OS)

    Overall Survival time (OS) is defined as the time from the date of treatment start to the date of death from any cause. The Participant without documented death at the last date of confirmation of survival or who is lost to follow-up will be censored at last date of confirmation of survival.

    Measured: 2 years

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

    The response rate is defined as the proportion of participants who have CR, PR, or stable disease (SD).

    Measured: 2 years

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

    The duration of response (DOR) is defined as the time from the first documented evidence of confirmed CR or PR to the first documentation of PD or death due to any cause (whichever is earlier), for participants who demonstrate a confirmed CR or PR.

    Measured: 2 years

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

    The best overall response is 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.

    Measured: 2 years

  6. Incidence of adverse events

    Safety, as defined by the rate of any adverse events as assessed by the Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v.5.0)

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2024
  2. Study start13 Mar 2024
  3. Primary completion30 Jun 2026
  4. Study completion30 Oct 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
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.
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06318286
Sponsor's protocol ID
MK3475-IIT-60977
Acronym
PENINSULA
Status last verified
Jul 2026
First submitted
27 Feb 2024
Last updated
16 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lenvatinib, Pemetrexed and Cisplatin/Carboplatin in people with Malignant Pleural Mesothelioma, run by Hyogo Medical University at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tumor shrinkage (response rate) (Physician Judgment by Medical Institution, Modified RECIST [Response Evaluation Criteria in Solid Tumors] criteria) (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06318286.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.

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