E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
unresectable malignant pleural mesothelioma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059518 |
E.1.2 | Term | Pleural mesothelioma malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
1. To describe the safety of pembrolizumab- lenvatinib in patients with MPM. 2. To describe the disease control rate (DCR) at 3 and 6 months, clinical benefit, progression free survival (PFS), overall survival (OS) and duration of response (DOR) 3. To describe ORR and PFS by independent radiological review |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically diagnosed malignant pleural mesothelioma, age at least 18 years 2. Progressive disease after nivolumab plus ipilimumab for unresectable MPM 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 immunotherapy, 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 chemotherapy 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 |
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E.4 | Principal 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 chemotherapy or dendritic cell therapy 4. concomitant administration to any other experimental drugs under investigation ≤ 4 weeks prior to first admission of pembrolizumab- lenvatinib |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. The proportions of patients with an objective response, defined by Modified RECIST 1.1 criteria for malignant pleural mesothelioma (see appendix C), determined by the local physician and compare ORR with historical controls. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumor response assessments will be performed using the same radiographic procedure used to assess disease sites at screening, and will be performed every 6 (±1) weeks for the first 48 weeks of treatment and every 12 (±1) weeks thereafter, until disease progression is documented. Tumor evaluation will be assessed by the investigator using Modified RECIST 1.1 Criteria for malignant pleural Mesothelioma |
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E.5.2 | Secondary end point(s) |
1. Extent of exposure, AEs, SAEs, treatment related AEs (TRAEs/SAEs) , AE’s leading to discontinuation of study drug(s)/withdrawal, fatal TRAEs and deaths. Other AEs that the investigator deemed important to report and reasons for discontinuation of study drug(s). AE grading will be performed by NCIE Common Terminology Criteria for Adverse Events Version 5.0. 2. To estimate the disease control rate (DCR) progression-free survival (PFS) determined by defined by Modified RECIST 1.1 criteria for malignant pleural mesothelioma Duration of response (DOR) (all determined by the local physician) and overall survival (OS). 3. To describe the DCR, ORR, DOR and PFS by independent radiological review |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
AEs ans SAEs: All adverse events/SAEs and concomitant medication will be recorded from the time the consent form is signed through 90 days after termination of anti-cancer therapy or earlier in case of a subsequent treatment line. Concomitant medication will be recorded from the time the consent form is signed through 30 days after termination of anti-cancer therapy or earlier in case of a subsequent treatment line
(DCR) at 3 and 6 months. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |