Table 3.

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

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