Mesothelioma Stratified Therapy (MiST) : A Multi-drug Phase II Trial in Malignant Mesothelioma

Mesothelioma Stratified Therapy (MiST): A Stratified Multi-arm Phase IIa Clinical Trial to Enable Accelerated Evaluation of Targeted Therapies for Relapsed Malignant Mesothelioma

Sponsors

Lead Sponsor: University of Leicester

Collaborator: British Lung Foundation
Clovis Oncology, Inc.
Eli Lilly and Company
Merck Sharp & Dohme Corp.
BerGenBio ASA
Roche Pharma AG
University Hospitals, Leicester
The Christie NHS Foundation Trust

Source University of Leicester
Brief Summary

MiST is a British Lung Foundation funded, University of Leicester Study, a multi-arm stratified therapy based clinical trial for patients with relapsed mesothelioma.

The goal of MiST is to enable acceleration of novel, effective personalised therapy as a basis for improving survival outcomes for patients with mesothelioma.

Detailed Description

Stage 1 - molecular pre-screening:

The MiST Master protocol describes the identification of patients, biomarker testing and analysis. Patients with relapsed mesothelioma will be offered to consent for molecular panel testing of their diagnostic tumour block for predictive biomarkers. The results of this assessment will be used to classify patients into one of several possible molecularly defined treatment arms. Patients will therefore be offered a specific study treatment determined by their molecular profile. Patients, who exhibit positive testing in more than one biomarker, will potentially be eligible to subsequently be treated on a different treatment protocol upon disease progression or treatment failure.

Stage 2 - Treatment:

The MiST treatment protocol will be specific to the treatment allocated to the patient - based on the results of their biomarker testing in stage 1.

Specific agent(s) will be detailed separately in each of the separate treatment protocols.

Stage 3 - Molecular Profiling :

In order to understand the genomic basis of drug response in the MiST trial, archival tumour tissue from all patients enrolled will be interrogated using molecular inversion probe- based microarray analysis of the somatic copy number aberrations. Optional re-biopsy of patients who progress on treatment, followed confirmed radiological response, will be offered, to investigate genomic interrogation of tumours at the time of acquired resistance. For arms 3 and 4, immune checkpoint, transcriptomic and gut microbiome correlative studies are planned.

Overall Status Recruiting
Start Date January 28, 2019
Completion Date November 30, 2021
Primary Completion Date July 30, 2021
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Disease control rate (DCR) at 12 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma. 12 weeks
Secondary Outcome
Measure Time Frame
Disease control rate (DCR) at 24 weeks assessed by modified RECIST 1.1, in patients with relapsed mesothelioma. 24 weeks
Objective response rate (ORR) assessed for 12 months Up to 12 months (up to 6 months during treatment and 6 months of follow-up)
Safety assessed according to CTCAE criteria. 12 months (up to 6 months during treatment and 6 months of follow-up)
Toxicity assessed according to CTCAE criteria. 12 months (up to 6 months during treatment and 6 months of follow-up)
Enrollment 120
Condition
Intervention

Intervention Type: Drug

Intervention Name: Rucaparib

Description: PARP inhibitor

Arm Group Label: MiST1 Rucaparib

Other Name: CO-338

Intervention Type: Drug

Intervention Name: Abemaciclib

Description: CDK4/6 inhibitor

Arm Group Label: MiST2 Abemaciclib

Other Name: LY2835219

Intervention Type: Drug

Intervention Name: pembrolizumab & bemcentinib

Description: PD1 checkpoint inhibitor, AXL inhibitor

Arm Group Label: MiST3 Pembrolizumab & Bemcentinib

Other Name: Keytruda; BGB324

Intervention Type: Drug

Intervention Name: Atezolizumab & Bevacizumab

Description: PDL1 checkpoint inhibitor, VEGF inhibitor

Arm Group Label: MiST4 Atezolizumab & Bevacizumab

Other Name: MPDL3280A; Avastin

Eligibility

Criteria:

INCLUSION CRITERIA FOR PRE-SCREENING

- Histologically confirmed MM with an available biopsy for research purposes

- Male or female patients aged ≥18 years.

- Expected survival of ≥12 weeks or greater

- ECOG PS 0-1

- CT scan chest, abdomen (and pelvis if applicable) confirming disease progression.

- Patients must have received at least one prior line of therapy to include a platinum doublet first-line chemotherapy (within or outside of another clinical trial)

- Willing to consent for molecular screening of archived tumour block (PIS1 & CF1)

EXCLUSION CRITERIA FOR PRE-SCREENING

- Patients with a diagnosis of a second malignancy except prostate or cervical cancer in remission, patients with a diagnosis of basal cell carcinoma of the skin or superficial bladder cancer.

- Uncontrolled CNS disease. Asymptomatic brain metastases are allowed if previously treated with radiotherapy >28 days prior to starting the investigational agent.

- New York Heart Association Class II or greater congestive heart failure.

- Patients with severe hepatic insufficiency or severe renal impairment.

- Patients requiring long term oxygen therapy.

- Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

Each individual MiST drug protocol contains the eligibility criteria specific to the treatment allocated to the patient.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Overall Contact

Last Name: Amy King, MSc

Phone: +44 (0)116 229

Phone Ext.: 7249

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Investigator: University Hospitals of Leicester NHS Trust Molly Scotland, Nurse 0116 204 7872 Dean Fennell, PhD, FRCP Principal Investigator
Location Countries

United Kingdom

Verification Date

January 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: MiST1 Rucaparib

Type: Experimental

Description: BRCA1/BAP1 negative mesothelioma; 600mg twice daily (BID) every 28 days.

Label: MiST2 Abemaciclib

Type: Experimental

Description: p16INK4A negative mesothelioma; 200mg orally twice daily every 28 days.

Label: MiST3 Pembrolizumab & Bemcentinib

Type: Experimental

Description: No specific biomarker requirement: Pembrolizumab 200mg IV infusion on Day 1 only: Bemcentinib loading dose of 400mg on days 1-3, on day 4 on-wards 200mg daily every 21-days.

Label: MiST4 Atezolizumab & Bevacizumab

Type: Experimental

Description: PDL1 expression positive mesothelioma: Atezolizumab 1200 milligrams via intravenous nfusion; Bevacizumab 15 milligrams per kilogram via IV infusion both on Days 1 every 21-days.

Acronym MiST
Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov