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

NCT04287829 | Active Not Recruiting Phase 2

• 1 other identifier: N19PEM
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

Conditions

Mesotheliomas Pleural

Outcome Measures

Primary Outcomes (1)

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

  Complete response and partial response

  Through study completion, an average of 1 year

Secondary Outcomes (4)

• Safety of pembrolizumab- lenvatinib

  Up to 90 days after last study drug intake

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

  From date of registration until 6 months

• Objective response rate (ORR)

  Assessed up to 60 months

• Progression-free survival

  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

Other Outcomes (1)

• Immunological status

  before study and after 6 weeks of treatment

Study Arms (1)

pembrolizumab and lenvatinib

EXPERIMENTAL

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

Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab DRUG

Infusion

pembrolizumab and lenvatinib

Lenvatinib DRUG

Capsule

pembrolizumab and lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify 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 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

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Antoni van Leeuwenhoekziekenhuis (NKI-AVL)

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 41308680 DERIVED

• 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.

  PMID: 37844598 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• S Burgers, PhD

  NKI-AvL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2019
• First Posted: February 27, 2020
• Study Start: March 1, 2021
• Primary Completion: December 5, 2024
• Study Completion: March 5, 2026
• Last Updated: November 5, 2024

Record last verified: 2024-11

Locations

NL (1)