JME-001 phase II trial of first-line combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma

Our plain-English summary of JME-001 phase II trial of first-line combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma, by Y. Miyamoto, T. Kozuki, K. Aoe, et al (Journal for Immunotherapy of Cancer, 2021).

The study

• Authors: Y. Miyamoto, T. Kozuki, K. Aoe, S. Wada, D. Harada, M. Yoshida, J. Sakurai, K. Hotta, N. Fujimoto
• Journal: Journal for Immunotherapy of Cancer
• Published: 2021;9(10)
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: JME-001 is a phase II trial assessing the efficacy and safety of cisplatin, pemetrexed, and nivolumab as first-line therapy in malignant pleural mesothelioma (MPM).

Patients And Methods: Patients with untreated, unresectable MPM with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 were included. The primary endpoint is the centrally reviewed objective response rate. The secondary endpoints include (1) response rate assessed by investigators, (2) disease control rate, (3) overall survival, (4) progression-free survival, (5) duration of response, and (6) time to response. Safety and adverse events will also be evaluated. Cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and nivolumab (360 mg/body) were administered intravenously every 3 weeks with a total of 4-6 cycles. If patients did not progress during the combination phase, maintenance therapy with nivolumab was administered until disease progression or unacceptable toxicity. Tissue samples were required and collected for programmed death ligand 1 analysis.

Results: Eighteen patients (mean age 69.2 years, 15 men) were enrolled between January 2018 and May 2019. The ECOG PS was 0 in 3 patients and 1 in 15 patients. Fourteen (77.8%; 95% CI 52.4% to 93.6%) patients had an objective response. The disease control rate was 94.4% (95% CI 72.7% to 99.9%). Fourteen (77.8%) patients had partial response (PR), three had stable disease, and one was not evaluable. Tumor shrinkage was observed in 10/14 (71.4%) patients with epithelioid, and 2/2 (100%) patients with sarcomatoid or biphasic histological subtype had PR. Ten (55.6%) patients experienced grade 3 or worse adverse events, including disorder of metabolism or nutrition (33.3%), loss of appetite (27.8%), anemia (16.7%), and hyponatremia (11.1%). No treatment-related deaths occurred.

Conclusions: The safety and efficacy of this study strongly support a definitive trial of this combination.Trial registration numberUMIN000030892.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

In plain English

This phase II trial in Japan tested a first treatment for malignant pleural mesothelioma that could not be surgically removed. It did not study asbestos exposure. Eighteen untreated patients, enrolled January 2018 to May 2019, were scheduled for 4 to 6 three-weekly cycles of cisplatin, pemetrexed and nivolumab, and actually received 2 to 6 cycles (average 4.8). Those whose disease had not worsened then continued on nivolumab alone. There was no comparison group. By central review, 14 of 18 patients (77.8%; 95% CI 52.4% to 93.6%) had a partial response, 3 had stable disease and 1 could not be evaluated. Disease control was reached in 17 of 18 (94.4%; 95% CI 72.7% to 99.9%). Median progression-free survival was 8.02 months (95% CI 5.59 to 14.06). Median overall survival was 20.8 months, but only 2 deaths had occurred by data cut-off. Ten patients (55.6%) had grade 3 or worse adverse events, and no treatment-related deaths were recorded. The authors concluded the combination showed sufficient activity and safety, but should be tested in a definitive randomized study. They noted the single-arm design, small trial size and immature survival data as limitations.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-arm, prospective, non-randomized, non-comparative, open-label, multicenter phase II clinical trial (drug treatment trial)
• Who was studied: 18 patients with untreated, unresectable malignant pleural mesothelioma and ECOG performance status 0 or 1, at four centers in Japan, enrolled January 2018 to May 2019 (15 men, 3 women; median age 69, range 64 to 78; 14 epithelioid, 2 sarcomatoid, 2 biphasic)
• Exposure: No asbestos exposure was studied. The planned intervention was intravenous cisplatin (75 mg/m2), pemetrexed (500 mg/m2) and nivolumab (360 mg/body) every 3 weeks for 4 to 6 cycles, followed by nivolumab maintenance until disease progression or unacceptable toxicity. Patients actually received an average of 4.8 cycles (range 2 to 6) of the three-drug combination
• Main results:
  • Patients received an average of 4.8 (range 2 to 6) cycles of the three-drug combination. Nine (50.0%) received four cycles and eight (44.4%) received six cycles
  • By central assessment, 14 of 18 patients (77.8%; 95% CI 52.4% to 93.6%) had an objective response, which matched the investigators' assessment
  • Best overall response among the 18 patients: 0 complete responses, 14 partial responses, 3 stable disease, 0 progressive disease, 1 not evaluable. Disease control rate was 94.4% (95% CI 72.7 to 99.9)
  • Tumor shrinkage was observed in 10 of 14 (71.4%) patients with epithelioid histology. The three remaining epithelioid patients had stable disease and one was not evaluable
  • The four patients with non-epithelioid disease (2 sarcomatoid, 2 biphasic) had a partial response
  • Tumor shrinkage occurred in 13 of 17 (76.5%) patients with PD-L1 expression of 1% or more, and in 1 of 1 patient with PD-L1 expression below 1%
  • Median duration of response was 6.7 months (95% CI 4.21 to not reached), and median time to response was 1.54 months (range 1.4 to 3.3)
  • Median progression-free survival was 8.02 months (95% CI 5.59 to 14.06). The 12-month progression-free survival rate was 40.3% (95% CI 16.2% to 63.5%)
  • Median overall survival was 20.8 months, with only 2 of 18 deaths (11.1%) and 16 patients censored at data cut-off. The 12-month overall survival rate was 92.3% (95% CI 56.6% to 98.9%)
  • All 18 patients had adverse events (all causes). Ten (55.6%) had grade 3 or greater adverse events, including loss of appetite (5 patients, 27.8%), anemia (3, 16.7%) and hyponatremia (2, 11.1%). No treatment-related death was recorded
  • Two patients (11.1%) developed peripheral neuropathy during nivolumab maintenance, which led to stopping treatment
• The authors' conclusion: The authors concluded that cisplatin, pemetrexed and nivolumab showed sufficient activity and safety as first-line therapy in unresectable malignant pleural mesothelioma. They thought adding nivolumab could be a treatment option, but stated that efficacy and safety should be examined in a definitive randomized study
• Limitations the authors state:
  • Single-arm, non-comparative design
  • Few participants lacked tumor PD-L1 expression
  • Survival analyses were immature because most participants were censored at data cut-off
  • Trial size was set by the ability to recruit patients, not by statistical power

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Chemotherapy, Cisplatin, Pemetrexed (Alimta), Nivolumab (Opdivo), Unresectable, Pleural Mesothelioma, First-line Therapy, Performance Status.

Related studies

• A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol — N. Fujimoto, K. Aoe, et al. (2018)
• Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial — G.L. Ceresoli, J.G. Aerts, et al. (2019)
• Phase I Trial of Cediranib in Combination with Cisplatin and Pemetrexed in Chemonaive Patients with Unresectable Malignant Pleural Mesothelioma (SWOG S0905) — A.S. Tsao, J. Moon, et al. (2017)
• A phase 1b clinical trial of the CD40-activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma — A.K. Nowak, A.M. Cook, et al. (2015)
• Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial — G.V. Scagliotti, R. Gaafar, et al. (2019)
• Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743 — A. Scherpereel, P. Baas, et al. (2026)

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