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

NCT ID: NCT04287829

Last Updated: 2024-11-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2026-03-05

Brief 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%. 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.

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.

Conditions

Mesotheliomas Pleural

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

pembrolizumab and lenvatinib

Patients 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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

Infusion

Lenvatinib

Intervention Type: DRUG

Capsule

Interventions

Pembrolizumab

Infusion

Intervention Type: DRUG

Lenvatinib

Capsule

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically diagnosed malignant pleural mesothelioma, age at least 18 years

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 (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.

3. 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

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 eligible

8. 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. (First cohort is closed).

11. No concomitant administration to any other experimental drugs under investigation ≤ 4 weeks prior to first admission of pembrolizumab- lenvatinib

12. 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.

13. No major injuries and/or surgery within the past 4 weeks prior to first study dose with incomplete wound healing

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 5Grade 1 or baseline. Participants with 52 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 imnnunotherapy) will be eligible in the first cohort. (CLOSED)

4. concomitant administration to any other experimental drugs under investigation 5 4 weeks prior to first admission of pembrolizumab- lenvatinib

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

S Burgers, PhD

Role: PRINCIPAL_INVESTIGATOR

NKI-AvL

Locations

Antoni van Leeuwenhoekziekenhuis (NKI-AVL)

Amsterdam, North Holland, Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 37844598 (View on PubMed)

Other Identifiers

N19PEM

Identifier Type: -

Identifier Source: org_study_id