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Mesotheliomas PleuralPhase 2PEMMELANCT04287829

Pembrolizumab Plus Lenvatinib In Second Line and Third Line Malignant Pleural mesotheLioma Patients

A Phase 2 study testing Pembrolizumab and Lenvatinib in people with Mesotheliomas Pleural, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Active, not recruiting

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

Official record
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Trial summary

There is no standard second line treatment in malignant pleural mesothelioma (MPM). Pembrolizumab has shown to be active in in small phase II studies in MPM. Its activity however, is limited, with a response rate up to 20%. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mesotheliomas Pleural
What is being tested?
Pembrolizumab and Lenvatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
1 siteNetherlands
Study dates
1 Mar 2021to 5 Mar 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

  • Histologically or cytologically diagnosed malignant pleural mesothelioma, age at least 18 years
  • Progressive disease after at least 1 and maximal 2 prior systemic treatment lines:
  • Cohort 1: patients, in which one of the lines contains a platinum-based doublet (both cisplatin and carboplatin are allowed) for unresectable MPM (CLOSED)
  • Cohort 2: patients with only in which one of the lines contains nivolumab-ipilimumab immunotherapy as first line treatment for unresectable MPM. No prior chemotherapy.
  • Measurable disease. At least one measurable lesion according to Modified RECIST 1.1 for pleural mesothelioma. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
  • WHO-ECOG performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to date of allocation
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  • Adequate organ function
  • Ability to understand the study and give signed informed consent (or legally acceptable representative if applicable) prior to beginning of protocol specific procedures including the approval of the thoracoscopy or transthoracic pleural biopsy before the first treatment cycle and an optional biopsy before the third treatment cycle
  • No presence of clinically relevant treatment-related toxicity from previous chemotherapy, targeted therapy and/or radiotherapy. Note: Participates must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤2 neuropathy may be eligible
  • No active uncontrolled infection, severe cardiac dysfunction (i.e. unstable angina, history of myocardial infarction within the past 12 months prior to screening, congestive heart failure > NYHA II, serious cardiac arrhythmia), unstable peptic ulcer, unstable diabetes mellitus or other seriously disabling condition
  • Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening ad no change in hypertensive medication within 1 week before the cycle 1/day1.
  • No prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with another agent agents direct to another stimulatory or co-inhibitory T-cell receptor (eg CTLA-4, OC-40, CD137) or TKI or antibody targeting angiogenesis in the first cohort. Patients who have been treated with autologous tumor cell vaccination (eg. Dendritic cell-based immunotherapy) will be eligible in the first cohort. (First cohort is closed).
  • No concomitant administration to any other experimental drugs under investigation ≤ 4 weeks prior to first admission of pembrolizumab- lenvatinib
  • No prior radiotherapy within 2 weeks before start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids as therapy for radiation induced toxicities. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  • No major injuries and/or surgery within the past 4 weeks prior to first study dose with incomplete wound healing

Who cannot join

  • presence of clinically relevant treatment-related toxicity from previous chemotherapy, targeted therapy and/or radiotherapy. Note: Participates must have recovered from all AEs due to previous therapies to 5Grade 1 or baseline. Participants with 52 neuropathy may be eligible
  • active uncontrolled infection, severe cardiac dysfunction (i.e. unstable angina, history of myocardial infarction within the past 12 months prior to screening, congestive heart failure \> NYHA II, serious cardiac arrhythmia), unstable peptic ulcer, unstable diabetes mellitus or other seriously disabling condition
  • prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with another agent agents direct to another stimulatory or co-inhibitory T-cell receptor (eg CTLA-4, OC-40, CD137) or TKI or antibody targeting angiogenesis in the first cohort. Patients who have been treated with autologous tumor cell vaccination (eg. Dendritic cell-based imnnunotherapy) will be eligible in the first cohort. (CLOSED)
  • concomitant administration to any other experimental drugs under investigation 5 4 weeks prior to first admission of pembrolizumab- lenvatinib

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Antoni van Leeuwenhoekziekenhuis (NKI-AVL)

    Amsterdam, North Holland, 1066 CX

Other trials in Netherlands

About this study

Official title: PEMbrolizumab Plus Lenvatinib In Second Line And Third Line Malignant Pleural MEsotheLiomA Patients(PEMMELA)

There is no standard second line treatment in malignant pleural mesothelioma (MPM). Pembrolizumab has shown to be active in in small phase II studies in MPM. Its activity however, is limited, with a response rate up to 20%. Since the arrival of nivolumab plus ipilimumab as first line standard of care treatment in mesothelioma, no treatment options are investigated in this group of patients in the second line. So, there is a need for new treatment combinations with drugs that might exhibit a synergistic interaction with pembrolizumab.

Read the detailed description

There is no standard second line treatment in malignant pleural mesothelioma (MPM). Pembrolizumab has shown to be active in in small phase II studies in MPM. Its activity however, is limited, with a response rate up to 20%. So, there is a need for new treatment combinations with drugs that might exhibit a synergistic interaction with pembrolizumab. The mechanisms of actions of lenvatinib, which has a broad spectrum of activities, predicts many synergistic interactions with PD-1 blocking. The aim of this study is to characterize the potential clinical activity, toxicity and biomarkers of outcome of pembrolizumab - lenvatinib in patients with recurrent MPM.

Medical subject headings
Mesothelioma, Malignant

What participants receive

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

Study groups in NCT04287829
Study groupRoleWhat they receive
pembrolizumab and lenvatinibExperimentalPatients will receive pembrolizumab 200mg/iv (fixed dose) every 3 weeks and lenvatinib 20mg QD in a three weekly cycle. Treatment continues until disease progression by modified RECIST 1.1 for MPM, severe toxicity, serious intercurrent illness, patient request for discontinuation, need or use for any other anti-cancer agent other than protocol treatment, except for palliative radiotherapy, for a maximum period of 35 cycles
Receives: Drug: Pembrolizumab; Drug: Lenvatinib

What is being measured

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

  1. Objective response rate defined by Modified RECIST 1.1 criteria for pleural mesothelioma

    Complete response and partial response

    Measured: Through study completion, an average of 1 year

Secondary outcomes (4)

  1. Safety of pembrolizumab- lenvatinib

    Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Measured: Up to 90 days after last study drug intake

  2. Describe the disease control rate (DCR) at 3 and 6 months

    a percentage of the total number of patients in the study who are evaluable for the primary endpoint who have best overall response of CR or PR or SD.

    Measured: From date of registration until 6 months

  3. Objective response rate (ORR)

    Number of patients with a partial or complete response

    Measured: Assessed up to 60 months

  4. Progression-free survival

    To describe PFS by independent radiological review

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Timeline

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

  1. First posted27 Feb 2020
  2. Study start1 Mar 2021
  3. Primary completion5 Dec 2024 (estimated)
  4. Study completion5 Mar 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
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04287829
Sponsor's protocol ID
N19PEM
Acronym
PEMMELA
Status last verified
Nov 2024
First submitted
15 Nov 2019
Last updated
5 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Douma LH, van der Noort V, Lalezari F, de Vries JF, Monkhorst K, Smesseim I, Baas P, Schilder B, Vermeulen M, Burgers JA, de Gooijer CJ. Pembrolizumab plus lenvatinib as second-line treatment in patients with pleural mesothelioma (PEMMELA): cohort 2 of a single-arm, phase 2 study. Lancet Oncol. 2025 Dec;26(12):1676-1684. doi: 10.1016/S1470-2045(25)00514-5.

    PubMed 41308680

  • Douma LH, Lalezari F, van der Noort V, de Vries JF, Monkhorst K, Smesseim I, Baas P, Schilder B, Vermeulen M, Burgers JA, de Gooijer CJ. Pembrolizumab plus lenvatinib in second-line and third-line patients with pleural mesothelioma (PEMMELA): a single-arm phase 2 study. Lancet Oncol. 2023 Nov;24(11):1219-1228. doi: 10.1016/S1470-2045(23)00446-1. Epub 2023 Oct 13.

    PubMed 37844598

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Lenvatinib in people with Mesotheliomas Pleural, run by The Netherlands Cancer Institute at 1 site in Netherlands.

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 15 inclusion and 4 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 5 Nov 2024. 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 Netherlands. 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?

Objective response rate defined by Modified RECIST 1.1 criteria for pleural mesothelioma (time frame: Through study completion, an average of 1 year). 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 NCT04287829, which also lists 2 linked publications.

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 5 Nov 2024.

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