Amatuximab and novel agents targeting mesothelin for solid tumors

Our plain-English summary of Amatuximab and novel agents targeting mesothelin for solid tumors, by P. Baldo, S. Cecco (OncoTargets and Therapy, 2017).

The study

• Authors: P. Baldo, S. Cecco
• Journal: OncoTargets and Therapy
• Published: 2017;10:5337-5353
• Type of article: Review
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelin (MSLN) is considered a promising target for cancer therapy. Originally extracted in 1992 after the immunization of mice with a human ovarian cancer (OC) cell line and cloned in 1996, MSLN seems to be involved in cell adhesion and metastasis. MSLN is prevalent in mesothelia tissues but is expressed in several human cancers, such as OC, pancreatic cancer, mesothelioma, and lung cancer. Amatuximab (MORAb-009) is a mouse-human chimeric monoclonal antibody with a selective affinity for MSLN. The principal mechanism of action comprises inhibition of binding of MSLN with the antigen CA125/MUC16. The highest phase of development is actually a Phase II trial (MORAb-009-201, Europe). In this review, we describe the mechanism of action of amatuximab and other MSLN-targeting novel drugs, along with a discussion about the expected efficacy, safety, and toxicity of this promising group of agents and implications for future research and clinical practice.

In plain English

This article was a narrative review, not an original study. The authors described mesothelin, a protein on normal mesothelial cells, overexpressed in mesothelioma, ovarian, pancreatic, lung and other cancers. They reviewed drugs that target it, chiefly the antibody amatuximab (MORAb-009), using published studies and registered clinical trials. Citing other work, they named asbestos inhalation as the most important risk factor for malignant mesothelioma. One reviewed Phase II trial gave amatuximab with pemetrexed and cisplatin to 89 patients with unresectable malignant pleural mesothelioma. It reported a median overall survival of 14.8 months (95% confidence interval 12.4 to 18.5 months) and an objective response rate of 39%, but progression-free survival was not improved. Across Phase I and II studies, 54.2% to 76.5% of patients had side effects considered linked to amatuximab, and one patient died of interstitial lung disease. In a pancreatic cancer trial, the gemcitabine plus placebo arm did better than the amatuximab arm, but no statistical analysis was provided. The authors concluded that amatuximab had an acceptable safety profile but only modest results used alone, and that mesothelin is a promising target.

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: Narrative review of mesothelin as a cancer drug target and of amatuximab and other mesothelin-targeting agents, with tables of clinical trials
• Who was studied: No patients were studied directly. The authors reviewed published studies and clinical trials, mostly listed on ClinicalTrials.gov, of mesothelin-targeting agents in mesothelioma and other solid tumors (pancreatic, ovarian, lung, breast, gastric and others).
• Exposure: No asbestos exposure was studied. The 'exposure' is drug treatment: amatuximab and other agents targeting mesothelin, namely the antibody-drug conjugates anetumab ravtansine, DMOT4039A and BMS-986148, the immunotoxins SS1P and LMB-100, the vaccine CRS-207, and CAR T-cells.
• Main results:
  • Background statement cited from other sources, not a finding of this review: inhalation of asbestos was described as the most important risk factor for malignant mesothelioma.
  • Reviewed Phase II trial NCT00738582 enrolled 89 patients with unresectable malignant pleural mesothelioma who had not had chemotherapy.
  • In that trial, amatuximab plus pemetrexed/cisplatin was reported with a median overall survival of 14.8 months and an objective response rate of 39%. The authors called these results encouraging.
  • Table 2 gave the 95% confidence interval for that trial's overall survival as 12.4 to 18.5 months.
  • In the same trial, progression-free survival (the primary objective) was not improved compared to controls.
  • In reviewed Phase I and II studies, 54.2% to 76.5% of patients had adverse events considered associated with amatuximab treatment.
  • One patient was reported to have died of interstitial lung disease, attributed to an adverse event of amatuximab.
  • In the reviewed Phase II pancreatic cancer trial (NCT00570713), the gemcitabine plus placebo arm showed better results than amatuximab for overall survival, progression-free survival and best response, but no statistical analysis was provided.
  • Citing other studies, mesothelin was described as overexpressed in up to 95% of patients with the epithelioid form of malignant mesothelioma and not overexpressed in the sarcomatoid form.
• The authors' conclusion: The authors concluded that amatuximab has an acceptable safety profile but shows only modest results as a single agent, that combinations with chemotherapy showed activity in Phase II trials, and that mesothelin is a promising target for several cancers.
• Limitations the authors state:
  • The authors noted that few clinical trial data on CAR T-cells had been published.
  • The authors noted that the role of mesothelin in cancer progression is not yet completely understood.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Ovarian Cancer, Metastasis, Mesothelioma, Lung Cancer, Monoclonal Antibody.

Related studies

• Phase I study of amatuximab, a novel monoclonal antibody to mesothelin, in Japanese patients with advanced solid tumors — Y. Fujisaka, T. Kurata, et al. (2015)
• Novel Antibody Therapeutics Targeting Mesothelin In Solid Tumors — X.Y. Zhao, B. Subramanyam, et al. (2016)
• Mesothelin-targeting T cells bearing a novel T cell receptor fusion construct (TRuC) exhibit potent antitumor efficacy against solid tumors — J. Ding, S. Guyette, et al. (2023)
• First-in-human study of a thorium-227-labeled mesothelin-targeting antibody-chelator conjugate (MSLN-TTC), in patients with malignant mesothelioma and other solid tumors — A. Minchom, O. Lindén, et al. (2025)
• Anetumab ravtansine: a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect — S. Golfier, C. Kopitz, et al. (2014)
• Inhibition of mesothelin as a novel strategy for targeting cancer cells — K. Wang, V. Bodempudi, et al. (2012)

Browse more research in OncoTargets and Therapy, or return to medical research.