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PEMbrolizumab Plus Lenvatinib In Second Line And Third Line Malignant Pleural MEsotheLiomA Patients: A Single Arm Phase II Study (PEMMELA).
EU CTIS ID: 2024-516618-39-00
What this study is testing
To determine the objective response rate (ORR), defined by Modified RECIST 1.1 criteria for pleural mesothelioma, of the combination of pembrolizumab - lenvatinib in pre-treated patients with MPM
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Histologically or cytologically diagnosed malignant pleural mesothelioma, age at least 18 years
- A male participant who agrees to use contraception as detailed in age and reproductive status breastfeeding (see 4.3.1.2 Age and reproductive status) (contraceptive methods appendix G)
- Anticipated life expectancy of ≥3 months
- 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 - Cohort 2: patients with only 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
You likely can't join if
- 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
- Symptomatic and/or hemorrhagic brain metastases
- Known hypersensitivity to trial drug or their excipients
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger. Hormone replacement like eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc. are permitted. Inhaled or topical steroids are not considered a form of systemic treatment.
- 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
- History of (non-infectious) pneumonitis that required steroids and no current pneumonitis
See the full eligibility criteria
Who can join
- Histologically or cytologically diagnosed malignant pleural mesothelioma, age at least 18 years
- A male participant who agrees to use contraception as detailed in age and reproductive status breastfeeding (see 4.3.1.2 Age and reproductive status) (contraceptive methods appendix G)
- Anticipated life expectancy of ≥3 months
- 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 - Cohort 2: patients with only 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
- Adequate organ function, including : Hematological Hematologisch o Absolute neutrophil count ≥ 1.5 x 109/l o Platelets≥ 150 x 109/l o Hemoglobin ≥6,0 mmol/l (9.0g/dL) Hepatic o Total serum bilirubin ≤ 1.5 times within the upper limits of normal (ULN) (except for Gilbert disease) o ASAT and ALAT < 2.5x ULN o AP (alkaline phosphatases) < 5x ULN (unless bone metastases are present in the absence of any liver disease). Renal o Proteinuria ≤ Grade 2 NCI CTCAE 5.0. Subjects having >1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subject with urine protein ≥1 g/24-hour will be ineligible. o Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 40mL/min Coagulation o INR ≤ 1.5 x ULN unless patients is receiving anticoagulant therapy as long as INR is within therapeutic range of intended use of anticoagulants
- 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
- Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in hypertensive medication within 1 week before the cycle 1/day1.
- A female is eligible if she is not pregnant and not breastfeeding (see 4.3.1.2. Age and reproductive status) (contraceptive methods appendix G)
- Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception to avoid pregnancy during treatment and for 120 days a
What rules you out
- 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
- Symptomatic and/or hemorrhagic brain metastases
- Known hypersensitivity to trial drug or their excipients
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger. Hormone replacement like eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc. are permitted. Inhaled or topical steroids are not considered a form of systemic treatment.
- 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
- History of (non-infectious) pneumonitis that required steroids and no current pneumonitis
- Known history of Human Immunodeficiency Virus (HIV) and/or known history of active TB (Bacillus Tuberculosis) and/or kwon history of hepatitis B or known active Hepatitis C virus
- Known other malignancy that is progressing or has required active treatment during the previous two years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 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 immunotherapy) will be eligible.
- Concomitant administration to any other experimental drugs under investigation ≤ 4 weeks prior to first admission of pembrolizumab- lenvatinib
- 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.
- Major injuries and/or surgery within the past 4 weeks prior to first study dose with incomplete wound healing
- History of clinically significant hemorrhagic or thromboembolic event within 6 months of screening
- Known inherited predisposition to bleeding or thrombosis
- Live vaccine within 4 weeks prior to the first dose of study drug
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.