MESO-PRIME

  • Research type

    Research Study

  • Full title

    MESO-PRIME: Pembrolizumab and Hypofractionated Stereotactic Radiotherapy in patients with Malignant Pleural Mesothelioma

  • IRAS ID

    224781

  • Contact name

    Fiona McDonald

  • Contact email

    fiona.mcdonald@rmh.nhs.uk

  • Sponsor organisation

    Royal Marsden NHS Foundation Trust

  • Eudract number

    2017-000769-65

  • Duration of Study in the UK

    2 years, 11 months, 31 days

  • Research summary

    This is a 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.

    The study will be conducted in two parts; an initial safety SBRT dose phase (Part A), followed by a SBRT dose expansion cohort (Part B). The dose escalation phase is based on a 3+3 design. A maximum of 6 patients will be allocated to Part A exploring SBRT 30 Gy in 3 fractions in combination with pembrolizumab. If there is one DLT in the first 3 patients or two or more DLTs in the first 6 patients, this treatment combination will be deemed as being unacceptable and it would lead to termination of the study. During the dose expansion cohort, 12 patients will have SBRT 30 Gy in 3 fractions with pembrolizumab to obtain additional safety and response data. Maintenance pembrolizumab will continue until disease progression, unacceptable toxicities, the patient withdraws consent to the trial, or the patient has completed 24 months of treatment. A maximum of 18 patients will be treated in the study.

    All patients will receive pembrolizumab on cycle (C) 1 day (D) 1, in Part A and B of the study. All patients will receive SBRT on C1D15, C1D17 and C1D19, as per SBRT protocol (See Appendix 3). Patients in part A will receive SBRT 30 Gy in 3#. Patients in Part B will receive 30 Gy in 3 fractions if considered safe after part A. All patients in Part A and Part B will receive pembrolizumab dosed at 200 mg every 3 weeks, until disease progression, unacceptable toxicities, the patient withdraws consent from the trial or the patient has completed 24 months of treatment.

    In the Initial safety cohort, a minimum of 3 patients will be required being assessed. A minimum gap of 1 week will be left between the treatment of the first and the second and between the second and the third patients with the combination of pembrolizumab and SBRT to mitigate against multiple patients suffering from acute toxicity. The DLT period for this study is 12 weeks from the last dose of SBRT (i.e. at C6D1). Patients included in Part A will be considered by the Safety Review Committee (SRC) once the 3rd or 6th patient in the Part A cohort has completed the DLT period. If 1 out of 3 patients experience a DLT in Part A, then the cohort will be expanded to 6 patients. If 1 in 6 patients experience a DLT, then it will acceptable to move forward to Part B with the dose of 30 Gy in 3#. However, if ≥ 2 in 6 patients experience a DLT then the maximum administered dose (MAD) will have been reached. If the MAD is seen at a dose level of 30 Gy in 3# then the study will be terminated.
    While waiting for 3 or 6 patients to complete the DLT period, no additional patients will be recruited. Further patients can only be recruited after the SRC has reviewed the toxicity data for the cohort. proceed to Part B. If there is ongoing clinical benefit at 24 months, the CI/PI will need to discuss with the sponsor and MSD, on a case by case basis for the continuation of pembrolizumab.

  • REC name

    London - Surrey Borders Research Ethics Committee

  • REC reference

    19/LO/0200

  • Date of REC Opinion

    22 May 2019

  • REC opinion

    Further Information Favourable Opinion