Pembrolizumab and Hypofractionated Stereotactic Radiotherapy in Patients With Malignant Pleural Mesothelioma

NCT04166734 | Terminated Phase 1 Results DMC

• 1 other identifier: CCR4583
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multi-centre non-randomised open-label phase 1 trial of pembrolizumab given in combination with SBRT to part of a pleural-based lesion in patients with unresectable MPM. This study will recruit up to 18 patients whose MPM has progressed beyond first-line of palliative chemotherapy, with a platinum-based doublet, and now requires further palliative systemic treatment, or have declined first-line palliative chemotherapy, however must have been considered suitable for a platinum doublet chemotherapy.

Conditions

Advanced Malignant Pleural Mesothelioma

Keywords

Advanced malignant pleural mesothelioma; mesothelioma; pembrolizumab; radiotherapy; SBRT; External Beam Stereotactic Body Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Dose Limiting Toxicity (DLT)

  Dose limiting toxicity is assessed using CTCAE v5.0 and defined as any one of: neutropenia with fever grade\>=3; neutropenia grade\>=4; thrombocytopenia with bleeding grade \>=3; thrombocytopenia grade \>=4; any non-haematological toxicity grade \>=3 which is definitely, probably or possibly related to the combination of pembrolizumab and SBRT

  Worst grade as assessed at cycle 1 day 1 of pembrolizumab, at each of three radiotherapy fractions (cycle 1 days 15, 17, 19) and then at day 1 of each 21 day cycle, up to 12 weeks from last dose of SBRT (i.e. cycle 6 day 1)

Secondary Outcomes (7)

• Worst Acute Toxicity Grade

  Worst grade as assessed at cycle 1 day 1 of pembrolizumab, at each of three radiotherapy fractions (cycle 1 days 15, 17, 19) and then at day 1 of each 21 day cycle, up to 12 weeks from last dose of SBRT (i.e. cycle 6 day 1)

• Overall Response Rate

  Response assessed from start of pembrolizumab, every 9 weeks for the first 6 months, then every 12 weeks thereafter, until the first instance of documented disease progression, start of new anti-cancer treatment, death or end of study (24 months)

• Disease Control Rate

  Response assessed from start of pembrolizumab, every 9 weeks for the first 6 months, then every 12 weeks thereafter, until the first instance of documented disease progression, start of new anti-cancer treatment, death or end of study (24 months)

• Overall Survival (OS) at Six Months

  6 months after start of pembrolizumab treatment

• Overall Survival (OS) at Twelve Months

  12 months after start of pembrolizumab treatment

Study Arms (2)

Initial safety cohort

OTHER

Patients will receive an initial dose of pembrolizumab in week 1 dosed at 200 mg. They will then receive SBRT dosed at 30 Gy in 3 fractions (#) alternate days in week 3. Treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks.

Drug: Pembrolizumab; Radiation: Stereotactic Body Radiotherapy (SBRT)

Expansion cohort

OTHER

An additional 12 patients will be recruited for this cohort. Patients will receive an initial dose of pembrolizumab at 200 mg in week 1. This will be followed in by SBRT dosed at 30 Gy in 3 fractions (#) alternate days in week 3. Treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks.

Drug: Pembrolizumab; Radiation: Stereotactic Body Radiotherapy (SBRT)

Interventions

Pembrolizumab DRUG

Pembrolizumab will be continued dosed at 200 mg given every 3 weeks Drug: Pembrolizumab Pembrolizumab in week 1 dosed at 200 mg (prior to SBRT) and then treatment with pembrolizumab will be continued dosed at 200 mg given every 3 weeks.

Also known as: Keytruda

Expansion cohort; Initial safety cohort

Stereotactic Body Radiotherapy (SBRT) RADIATION

Stereotactic Body Radiotherapy (SBRT) 30 Gy 3 fractions (#)

Also known as: SBRT

Expansion cohort; Initial safety cohort

Eligibility Criteria

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

You may qualify if:

• Patients should be ≥18 years old on the day of signing the informed consent.
• Patients must have a histological or cytological diagnosis of MPM.
• Patients should have non-radically treatable MPM (i.e. not being considered for extrapleural pneumonectomy or pleurectomy and decortication).
• Patients must have measurable disease as assessed by mRECIST (i.e. at least a 1 cm rind of MPM at 2 sites on 3 different levels).
• Patients must have had disease progression or be intolerant of standard first-line palliative chemotherapy for MPM. Patients who have declined first-line palliative chemotherapy must have been suitable for platinum-doublet combination chemotherapy.
• Patient should have an ECOG performance status 0-1.
• Patients should be able to tolerate a course of stereotactic radiotherapy as assessed by the investigator.
• Patients should have pleural based disease, away from critical structures, and suitable for treatment to part of lesion with SBRT for pleural mesothelioma.
• Patients must have adequate organ function including MRC dyspnoea score \<3 and adequate baseline lung function tests, with an FEV1 \> 0.8L or \>30% of predicted and a TLCO \> 30%.
• Demonstrate adequate organ function (based on bloods within 10 days of C1D1).
• Have provided tissue from an archival tissue sample or newly obtained tissue sample.
• Female patient of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication (C1D1). Female patients of childbearing potential should be willing to use highly effective methods of contraception for the course of the study through 120 days after the last dose of study medication. Female of childbearing potential is defined as women following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
• Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Be willing to provide informed consent for the trial.

You may not qualify if:

• Patients who have taken any investigational medicinal product or have used an investigational device within 4 weeks of the first dose of pembrolizumab. Patients are allowed to participate in additional observational studies.
• Patients who have received prior chemotherapy, targeted small molecule therapy or radiotherapy within 4 weeks prior to the first dose of pembrolizumab.
• Patients with a diagnosis of immunodeficiency or be receiving systemic steroid therapy (\>7.5 mg of prednisone / \>1 mg of dexamethasone or their equivalent dose) or any other form of immunosuppressive therapy within 7 days prior to the first dose.
• Patients with evidence of active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents or an autoimmune disease that is currently quiescent off any treatment, but deemed at risk of a significant flare if treated on this protocol.
• Patients who have received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Patients with evidence of active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided the brain metastases are stable and there is no evidence of new or enlarging brain metastases.
• Patients who have had previous radiotherapy to the thorax or other neighbouring region that would preclude the safe administration of SBRT for MPM.
• Patients with evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Patients with evidence of additional malignancy that is progressing or requires active treatment.
• Patients with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound trial results, interfere with the patient's participation or is not in the best interest of the patient.
• Patients with psychiatric or substance abuse disorders that would interfere with patients participation.
• Patients who are pregnant / breastfeeding or expecting to conceive within the duration of the trial, starting with the screening visit through 120 days after the last dose.
• Patients with a history of HIV, HIV 1/2 antibodies, Hepatitis B or Hepatitis C.
• Patients with any active infection requiring systemic treatment
• Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• Royal Marsden NHS Foundation Trust: lead

Study Sites (2)

Royal Marsden NHS Foundation Trust

Chelsea, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

MeSH Terms

Conditions

Mesothelioma

Interventions

pembrolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: MESO-PRIME Trial Manager
• Organization: The Royal Marsden NHS Foundation Trust

Mesoprime.Trial@rmh.nhs.uk

(+44)2089156666

Study Officials

• Fiona McDonald

  Royal Marsden NHS Foundation Trust

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Initial safety phase followed by an Expansion phase

Study Record Dates

• First Submitted: November 8, 2019
• First Posted: November 18, 2019
• Study Start: February 12, 2021
• Primary Completion: July 25, 2023
• Study Completion: July 25, 2023
• Last Updated: February 4, 2026
• Results First Posted: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)