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Table 3 Clinical trials in MPM of single-agent checkpoint inhibitors within the second-line (salvage) setting

From: Emerging avenues in immunotherapy for the management of malignant pleural mesothelioma

Trial acronym or title Trial identifier Treatment Phase Primary objective (s) Completion date Report status References
MERIT
A multi-centre, open-label, uncontrolled, phase II study to investigate efficacy and safety of ONO-4538 in malignant pleural mesothelioma (ONO-4538–41(33–609))
JapicCTI-163247 Nivolumab II ORR according to mRECIST Primary Completion Date:
March 14, 2018
Completed
ORR: 29%
Median OS was 17.3 months
[55, 56]
DETERMINE
A Phase 2b, Randomized, Double-blind Study Comparing Tremelimumab to Placebo in Second- or Third-line Treatment of Subjects With Unresectable Pleural or Peritoneal Malignant Mesothelioma
NCT01843374 Temelimumab II OS (defined as time from randomisation until death from any cause) Actual Primary Completion Date:
January 24, 2016
Estimated Study Completion Date: December 31, 2020
Completed
Median overall survival did not differ significantly between the treatment groups: it was 7·7 months (95% CI 6·8–8·9) in the tremelimumab group vs 7·3 months (5·9–8·7) in the placebo group
(HR 0·92, 95% CI 0·76 − 1·12, p = 0·41)
[57]
PROMISE-Meso
A Multicentre Randomised Phase III Trial Comparing Pembrolizumab Versus Standard Chemotherapy for Advanced Pre-treated Malignant Pleural Mesothelioma
NCT02991482 Pembrolizumab vs institutional choice single-agent chemotherapy (gemcitabine or vinorelbine) in relapsed MPM patients with progression after/on previous platinum-based chemotherapy, and at progression, patients randomized to chemotherapy were allowed to crossover to Pembrolizumab III Progression Free Survival (PFS)
Secondary outcome: OS
Estimated Primary Completion Date: December 2020
Estimated Study Completion Date: December 2020
Completed
At a median 11.8 month follow-up, median PFS (95% CI) for pembrolizumab was 2.5 compared with 3.4 months for chemotherapy
no difference in OS was detected between groups
[58]
NivoMes NCT02497508 Nivolumab (3 mg/kg) administered every 2 weeks intravenously for a maximum of 12 months or until disease progression or unacceptable toxicity II Disease Control Rate (DCR) Actual Study Completion Date:
July 2017
Completed
The trial demonstrated a DCR of 50% and an ORR of 24%
median OS of 11.8 months
[59]
JAVELIN NCT01772004 Avelumab at 10 mg/kg every 2 weeks I Dose Limiting Toxicity
Best OR
Completion Date December 16, 2019
MPM arm completed July 22, 2015
Completed
Acceptable safety profile with grade 3 or 4 treatment related adverse event of 9% median OS of 10.7
[60]
Keynote-028
Phase IB Study of Pembrolizumab (MK-3475) in Subjects With Select Advanced Solid Tumors
NCT02054806 Basket trial across 20 different cohorts of patients with PD-L1–positive, advanced solid tumors (including MPM) to assess the antitumor effects of Pembrolizumab given 10 mg/kg every 2 weeks for 2 years or until confirmed disease progression or unacceptable toxicity occurred I ORR using Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) [ Time Frame: Up to 24 months] Estimated Study Completion Date: December 18, 2023 Interim
In 2017 an ORR of 20% was reported in the MPM cohort
The same ORR was reported for MPM in 2019 with a median PFS of 5.5 months and a median OS of 18.7 months
[61, 62]
Keynote-158
A Clinical Trial of Pembrolizumab (MK-3475) Evaluating Predictive Biomarkers in Subjects With Advanced Solid Tumors (KEYNOTE 158)
NCT02628067 Experimental arm 1: pembrolizumab 200 mg every 3 weeks (up to 2 years)
Experimental arm 2:
Patients with high tumour mutational burden (TMB) – excluding those with mismatch repair deficient (dMMR/MSI-H) receive 400 mg every 6 weeks (up to 2 years)
II Objective Response Rate (ORR) [Time Frame: Up to approximately 2 years] Estimated Study Completion Date:
June 18, 2026
Interim
For all cohorts an overall ORR of 29% in TMB high vs 6% in TMB low
In MPM an ORR was only observed in 9 of 84 TMB low cases
[63]
IRB14-1381 NCT02399371 Intravenous pembrolizumab every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity II Ability of PD-L1 to predict response
Secondary outcomes include: OS, PFS, DCR
Estimated Primary Completion Date:March 20, 2021
Estimated Study Completion Date: March 20, 2023
Interim
median OS of 11.5 months
[64]
An Efficacy and Safety Study of Avelumab Plus SBRT in Malignant Mesothelioma (MPM) NCT03399552 One dose of Avelumab (10 mg/kg) every other week as well as a short course of SBRT after the first two doses of avelumab I/II Overall response rate [Time Frame: 3 years] defined by modified RECIST 1.1 for mesothelioma Estimated Study Completion Date December 2021