PEMbrolizumab Plus Lenvatinib In Second Line And Third Line Malignant Pleural MEsotheLiomA Patients.

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 58

Inclusion Criteria

1. Histologically or cytologically diagnosed malignant pleural mesothelioma,
age at least 18 years
2. 2. 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 in which one of the lines contains
nivolumab-ipilimumab immunotherapy as first line treatment for unresectable
MPM. No prior chemotherapy.
3. Measurable disease. At least one measurable lesion according to Modified
(i)RECIST for pleural mesothelioma. Lesions situated in a previously irradiated
area are considered measurable if progression has been demonstrated in such
lesions
4. WHO-ECOG performance status of 0 to 1. Evaluation of ECOG is to be performed
within 7 days prior to date of allocation
5. Adequate organ function
6. 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
7. 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 eligible8. 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
9. 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.
10. 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.
11. No major injuries and/or surgery within the past 4 weeks prior to first
study dose with incomplete wound healing
12. No active autoimmune disease that has required systemic treatment in past 2
years (i.e., with use of disease modifying agents, corticosteroids or
immunosuppressive drugs).
13. A female is eligible if she is not pregnant and not breastfeeding. A male
participant who agrees to use contraception as detailed in age and reproductive
status breastfeeding

Exclusion Criteria

1. 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
2. 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
3. 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.
4. concomitant administration to any other experimental drugs under
investigation <= 4 weeks prior to first admission of pembrolizumab- lenvatinib

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary:<br /><br>1. To determine the objective response rate (ORR), defined by Modified RECIST<br /><br>1.1 criteria for pleural mesothelioma, of the combination of pembrolizumab-<br /><br>lenvatinib in pre-treated patients with MPM to be compared with historical<br /><br>controls. </p><br>

Secondary Outcome Measures