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 | |
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 11.8Â month follow-up, median PFS (95% CI) for pembrolizumab was 2.5 compared with 3.4Â months for chemotherapy no difference in OS was detected between groups | [58] |
NivoMes | NCT02497508 | Nivolumab (3Â mg/kg) administered every 2Â weeks intravenously for a maximum of 12Â 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 11.8Â months | [59] |
JAVELIN | NCT01772004 | Avelumab at 10Â mg/kg every 2Â 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 | |
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 21Â days for up to 24Â 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 11.5Â months | [64] |
An Efficacy and Safety Study of Avelumab Plus SBRT in Malignant Mesothelioma (MPM) | NCT03399552 | One dose of Avelumab (10Â 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: 3Â years] defined by modified RECIST 1.1 for mesothelioma | Estimated Study Completion Date December 2021 | Â | Â |