Online citations, reference lists, and bibliographies.
← Back to Search

Promising Investigational Drug Candidates In Phase I And Phase II Clinical Trials For Mesothelioma

A. Guazzelli, Emyr Bakker, K. Tian, C. Demonacos, M. Krstic-Demonacos, L. Mutti
Published 2017 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
ABSTRACT Introduction: Malignant mesothelioma is a rare and lethal malignancy primarily affecting the pleura and peritoneum. Mesothelioma incidence is expected to increase worldwide and current treatments remain ineffective, leading to poor prognosis. Within this article potential targets to improve the quality of life of the patients and assessment of further avenues for research are discussed. Areas covered: This review highlights emerging therapies currently under investigation for malignant mesothelioma with a specific focus on phase I and phase II clinical trials. Three main areas are discussed: immunotherapy (immune checkpoint blockade and cancer vaccines, among others), multitargeted therapy (such as targeting pro-angiogenic genes) and gene therapy (such as suicide gene therapy). For each, clinical trials are described to detail the current or past investigations at phase I and II. Expert opinion: The approach of applying existing treatments from other cancers does not show significant benefit, with the most promising outcome being an increase in survival of 2.7 months following combination of chemotherapy with bevacizumab. It is our opinion that the hypoxic microenvironment, the role of the stroma, and the metabolic status of mesothelioma should all be assessed and characterised to aid in the development of new treatments to improve patient outcomes.
This paper references
Anetumab Ravtansine: A Novel Mesothelin-Targeting Antibody–Drug Conjugate Cures Tumors with Heterogeneous Target Expression Favored by Bystander Effect
S. Golfier (2014)
Monoclonal antibody-based therapies in cancer: advances and challenges.
P. Sapra (2013)
Selective blockade of B7‐H3 enhances antitumour immune activity by reducing immature myeloid cells in head and neck squamous cell carcinoma
Liang Mao (2017)
The role of microenvironment and immunity in drug response in leukemia.
Emyr Bakker (2016)
The resistance related to targeted therapy in malignant pleural mesothelioma: Why has not the target been hit yet?
G. Bronte (2016)
Tumor necrosis factor.
P. Wakefield (1991)
Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells
P. Schuberth (2013)
[Malignant mesothelioma].
J. Espinosa Arranz (1994)
[Dendritic cell-based therapeutic cancer vaccines].
M. Rizzo (2016)
Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study.
L. Garland (2007)
Useful information on mesothelin and its place in mesothelioma therapy by Villena-Vargas and colleagues
Switching off malignant mesothelioma: exploiting the hypoxic microenvironment
Noushin Nabavi (2016)
Recent Advances in Immunotherapy in Metastatic NSCLC
P. Bansal (2016)
111In-Labeled CHX-A''-DTPA-conjugated MORAb-009, a chimeric monoclonal antibody directed against mesothelin. Molecular Imaging and Contrast Agent Database (MICAD). Bethesda (MD)2004
A. Chopra (2004)
Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers
Mesothelioma Epidemiology, Carcinogenesis, and Pathogenesis
H. Yang (2008)
Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial.
E. Alley (2017)
FAK in cancer: mechanistic findings and clinical applications
Florian J. Sulzmaier (2014)
Phase II study of asparagine-glycine-arginine-human tumor necrosis factor alpha, a selective vascular targeting agent, in previously treated patients with malignant pleural mesothelioma.
V. Gregorc (2010)
Cancer, Leukemia Group B. Gefitinib in patients with malignant mesothelioma: a phase II study by the Cancer and Leukemia
R Govindan (2005)
Combination Immunotherapy Superior to Monotherapy in Patients with Melanoma.
C. Doyle (2015)
Gene therapy in mesothelioma
U. Hengge (1998)
Ipilimumab in melanoma
P. Specenier (2012)
Suicide Gene Therapy for Cancer - Current Strategies.
P. Zarogoulidis (2013)
WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer
L. Krug (2010)
FDA Approval Summary: Nivolumab for the Treatment of Metastatic Non-Small Cell Lung Cancer With Progression On or After Platinum-Based Chemotherapy
D. Kazandjian (2016)
Institute between 1986 and 2006
C Boutin (2008)
A Phase II Study of Sorafenib in Malignant Mesothelioma: Results of Cancer and Leukemia Group B 30307
S. Dubey (2010)
CRS‐207 with chemotherapy (chemo) in malignant pleural mesothelioma (MPM): Results from a phase 1b trial: 208O_PR
T. Jahan (2016)
Wilms' tumor gene 1): biology and cancer immunotherapy
H Sugiyama
Cancer Vaccines
T. Greten (2001)
Gene therapy for mesothelioma. Current treatment options in oncology
A Vachani (2011)
Recombinant GM-CSF plus autologous tumor cells as a vaccine for patients with mesothelioma.
A. Powell (2006)
Clinical development of Listeria monocytogenes-based immunotherapies.
D. Le (2012)
Differences in Treatment Effect Size Between Overall Survival and Progression-Free Survival in Immunotherapy Trials: A Meta-Epidemiologic Study of Trials With Results Posted at
A. Tan (2017)
Therapy of cancer by cytokines mediated by gene therapy approach
Cheng Qian (2006)
Dendritic-cell-based therapeutic cancer vaccines.
K. Palucka (2013)
Epidermal growth factor receptor mutations in malignant pleural and peritoneal mesothelioma
Y. Enomoto (2012)
OA13.01 A Phase II Study of Nivolumab in Malignant Pleural Mesothelioma (NivoMes): with Translational Research (TR) Biopies
J. Quispel-Janssen (2017)
Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis
Rubens Chang (2016)
Prognostic significance of vascular endothelial growth factor, tumor necrosis, and mitotic activity index in malignant pleural mesothelioma.
F. Demirag (2005)
Immunotherapy of murine malignant mesothelioma using tumor lysate-pulsed dendritic cells.
J. Hegmans (2005)
Enhancement of Antitumor Immunity by CTLA-4 Blockade
D. Leach (1996)
111In-Labeled CHX-A''-DTPA-conjugated MORAb-009, a chimeric monoclonal antibody directed against mesothelin. Molecular Imaging and Contrast Agent Database (MICAD)
A. Chopra (2004)
Advances in malignant mesothelioma.
B. Robinson (2005)
Tremelimumab for patients with chemotherapyresistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial
L Calabro (2013)
Phase I study of amatuximab, a novel monoclonal antibody to mesothelin, in Japanese patients with advanced solid tumors
Y. Fujisaka (2014)
Phase I Clinical Trial of the Chimeric Anti-Mesothelin Monoclonal Antibody MORAb-009 in Patients with Mesothelin-Expressing Cancers
R. Hassan (2010)
Antibody targeting of TGFbeta in cancer patients
S Lonning (2011)
Cancer vaccines
L. Butterfield (2015)
doubleblind, placebo-controlled, randomized phase II trial of gemcitabine/ cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma
H L Kindler
Development of an Fcenhanced anti-B7-H3 monoclonal antibody with potent antitumor activity
D Loo (2012)
Immune modulation by dendritic-cell-based cancer vaccines
C. Kumar (2017)
Malignant pleural mesothelioma: update on treatment options with a focus on novel therapies.
A. Haas (2013)
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
P. Waterhouse (1995)
Immune Checkpoint Blockade in Cancer Therapy.
M. Postow (2015)
Cytokine gene therapy for malignant pleural mesothelioma.
A. Vachani (2007)
Phase I Trial of Continuous Infusion Anti-Mesothelin Recombinant Immunotoxin SS1P
R. Kreitman (2009)
Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma
C. Porta (2008)
Global Magnitude of Reported and Unreported Mesothelioma
Eun-Kee Park (2011)
CTLA-4 trafficking and surface expression.
Elke Valk (2008)
Preclinical Development of Ipilimumab and Nivolumab Combination Immunotherapy: Mouse Tumor Models, In Vitro Functional Studies, and Cynomolgus Macaque Toxicology
Mark Selby (2016)
Immunotherapy for malignant pleural mesothelioma. Current status and future prospects.
R. Wong (2014)
FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer.
M. Cohen (2007)
Gene therapy for malignant mesothelioma: beyond the infant years
R. Most (2006)
PROVENGE (Sipuleucel-T) in Prostate Cancer: The First FDA-Approved Therapeutic Cancer Vaccine
M. Cheever (2011)
Adoptive TCell Therapy Using Autologous Tumor-Infiltrating Lymphocytes for Metastatic Melanoma Current Status and Future Outlook
R Wu (2012)
Bevacizumab in combination with chemotherapy in platinum-sensitive ovarian cancer
C. Della Pepa (2014)
Phase 1 study of the antimesothelin immunotoxin SS1P in combination with pemetrexed and cisplatin for front‐line therapy of pleural mesothelioma and correlation of tumor response with serum mesothelin, megakaryocyte potentiating factor, and cancer antigen 125
R. Hassan (2014)
Phase II clinical trial of amatuximab, a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma.
R. Hassan (2014)
Current and prospective pharmacotherapies for the treatment of pleural mesothelioma
Emyr Bakker (2017)
Adoptive immunotherapy: engineering T cell responses as biologic weapons for tumor mass destruction.
W. Ho (2003)
EGFR overexpression in malignant pleural mesothelioma. An immunohistochemical and molecular study with clinico-pathological correlations.
A. Destro (2006)
•• Detailed review of immunotherapy in mesothelioma
Intrapleural treatment with recombinant gamma‐interferon in early stage malignant pleural mesothelioma
C. Boutin (1994)
Erlotinib plus bevacizumab in previously treated patients with malignant pleural mesothelioma
D. Jackman (2008)
[Table, 111In-Labeled CHX-A''-DTPA–conjugated MORAb-009, a chimeric monoclonal antibody directed against mesothelin].
A. Chopra (2012)
•• General overview of immune checkpoint blockade in cancer by Postow and colleagues
Consolidative dendritic cell-based immunotherapy elicits cytotoxicity against malignant mesothelioma.
J. Hegmans (2010)
Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma
L. Strizzi (2001)
Phase II Study of Belinostat (PXD101), a Histone Deacetylase Inhibitor, for Second Line Therapy of Advanced Malignant Pleural Mesothelioma
S. Ramalingam (2009)
Novel cancer antigens for personalized immunotherapies: latest evidence and clinical potential
G. Wurz (2016)
• Useful article on DC-based vaccines by Palucka and colleagues
FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma
Julia A. Beaver (2017)
Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer.
W. Kelly (2005)
A Phase I Clinical Trial of Single-Dose Intrapleural IFN-β Gene Transfer for Malignant Pleural Mesothelioma and Metastatic Pleural Effusions: High Rate of Antitumor Immune Responses
D. Sterman (2007)
Whole Tumor Antigen Vaccines: Where Are We?
C. Chiang (2015)
Gefitinib in Patients with Malignant Mesothelioma: A Phase II Study by the Cancer and Leukemia Group B
R. Govindan (2005)
WT1 (Wilms' tumor gene 1): biology and cancer immunotherapy.
H. Sugiyama (2010)
Epidermal growth factor receptor overexpression in malignant pleural mesothelioma: Prognostic correlations
O. Rena (2011)
Wilms' tumours: about tumour suppressor genes, an oncogene and a chameleon gene
V. Huff (2011)
Safety and efficacy of pembrolizumab in a patient with advanced melanoma on haemodialysis. BMJ case reports
R Chang (2016)
Selective blockade of B7H3 enhances antitumour immune activity by reducing immature myeloid cells in head and neck squamous cell carcinoma
L Mao (2017)
Vatalanib in malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B (CALGB 30107).
T. Jahan (2012)
Development of an Fc-Enhanced Anti–B7-H3 Monoclonal Antibody with Potent Antitumor Activity
D. Loo (2012)
Tumor necrosis factor.
W. Chu (2013)
Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial
G. Zalcman (2016)
High‐dose interleukin‐2 for the treatment of metastatic renal cell carcinoma
J. Klapper (2008)
Long-term Follow-up of Patients with Malignant Pleural Mesothelioma Receiving High-Dose Adenovirus Herpes Simplex Thymidine Kinase/Ganciclovir Suicide Gene Therapy
D. Sterman (2005)
Nivolumab in the Treatment of Hodgkin Lymphoma
S. Ansell (2016)
Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti–PD-L1 immunotherapy in pancreatic cancer
Christine Feig (2013)
Receptor tyrosine kinases: mechanisms of activation and signaling.
S. Hubbard (2007)
What's the place of immunotherapy in malignant mesothelioma treatments?
M. Grégoire (2010)
Long-term follow-up of patients with malignant pleural mesothelioma receiving highdose adenovirus herpes simplex thymidine kinase/ganciclovir suicide gene therapy
DH Sterman (2005)
Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains
C. Carpenito (2009)
Therapeutic cancer vaccines: past, present, and future.
C. Guo (2013)
Suicide Gene Therapy for Cancer – Current Strategies. Journal of genetic syndrome & gene therapy 2013;4:16849
P Zarogoulidis (2013)
Germline BAP1 mutations predispose to malignant mesothelioma
J. Testa (2011)
Cancer immunotherapy: the beginning of the end of cancer?
S. Farkona (2016)
Antibody targeting of TGF-beta in cancer patients
S Lonning (2011)
Phase II study of asparagineglycine-arginine-human tumor necrosis factor alpha, a selective vascular targeting agent, in previously treated patients with malignant pleural mesothelioma
V Gregorc (2010)
Monoclonal antibody-based therapies in cancer: advances and challenges. Pharmacology & therapeutics
P Sapra (2013)
Adoptive T cell therapy for cancer in the clinic.
C. June (2007)
Extended Tumor Control after Dendritic Cell Vaccination with Low-Dose Cyclophosphamide as Adjuvant Treatment in Patients with Malignant Pleural Mesothelioma.
R. Cornelissen (2016)
Antibody targeting of TGF-beta in cancer patients. Current pharmaceutical biotechnology
S Lonning (2011)
Cancer Immunotherapy: Sipuleucel‐T and Beyond
Aimee E. Hammerstrom (2011)
Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes for metastatic melanoma: current status and future outlook.
R. Wu (2012)
EGFR overexpression in malignant pleural mesothelioma. An immunohistochemical and EXPERT OPINION ON INVESTIGATIONAL DRUGS 943 molecular study with clinico-pathological correlations
A Destro (2006)
The Future Is Now: Chimeric Antigen Receptors as New Targeted Therapies for Childhood Cancer
D. Lee (2012)
Tremelimumab for the treatment of malignant mesothelioma
A. Guazzelli (2015)
Mesothelioma epidemiology, carcinogenesis, and pathogenesis. Current treatment options in oncology
H Yang (2008)
Targeted therapy with bevacizumab (Avastin) for metastatic colorectal cancer
G. Koukourakis (2011)
• Important study on bevacizumab in mesothelioma
The Interplay of Immunotherapy and Chemotherapy: Harnessing Potential Synergies
L. Emens (2015)
Antibody targeting of TGF-β in cancer patients.
S. Lonning (2011)
Mesothelin-targeted immunotherapies for malignant pleural mesothelioma.
Jonathan Villena-Vargas (2012)
Therapeutic antibodies: successes, limitations and hopes for the future
P. Chames (2009)
Efficacy and safety of an intensified schedule of tremelimumab for chemotherapy-resistant malignant mesothelioma: an open-label, single-arm, phase 2 study.
L. Calabrò (2015)
TGFβ in Cancer
J. Massagué (2008)
Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma.
Antonio J. Grillo-López (1999)
Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma.
H. Kindler (2012)
TGFbeta in Cancer
J Massague (2008)
Immunological effects of the TGFβ-blocking antibody GC1008 in malignant pleural mesothelioma patients
J. Stevenson (2013)
Preclinical evaluation of MORAb-009, a chimeric antibody targeting tumor-associated mesothelin.
Raffit Hassan (2007)
Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma: an open-label, single-arm, phase 2 trial.
L. Calabrò (2013)
Promising investigational drug candidates in phase I and phase II clinical trials for mesothelioma
C. Demonacos
Molecular pathogenesis of malignant mesothelioma.
P. Rascoe (2012)
The Use of Superlatives in Cancer Research.
M. Abola (2016)
Targeted therapies in the management of renal cell carcinoma: role of bevacizumab
B. Escudier (2008)
Clinical Significance of Serum Mesothelin in Patients with Mesothelioma and Lung Cancer
A. Cristaudo (2007)
Anti-CTLA-4 therapy for malignant mesothelioma.
A. Guazzelli (2017)
Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific redirected T cells
PC Schuberth (2013)
Molecular Imaging and Contrast Agent Database (MICAD)
Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment
A. Bibby (2016)

This paper is referenced by
MESOTIP: Phase II multicenter randomized trial evaluating the association of PIPAC and systemic chemotherapy vs. systemic chemotherapy alone as 1st-line treatment of malignant peritoneal mesothelioma
O. Sgarbura (2019)
What can independent research for mesothelioma achieve to treat this orphan disease?
A. Guazzelli (2019)
Current and Emerging Therapy for Malignant Pleural Mesothelioma: Focus on CD26/Dipeptidyl Peptidase IV as a Therapeutic Target
B. Doonan (2017)
Pleura and Peritoneum
Naoual Bakrin (2018)
Reduction of Antitumor Immunity Caused by Asbestos Exposure
Naoko Kumagai-Takei (2020)
BAP1 Status Determines the Sensitivity of Malignant Mesothelioma Cells to Gemcitabine Treatment
A. Guazzelli (2019)
Allergy and Immunotoxicology in Occupational Health - The Next Step
T. Otsuki (2020)
New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma
Marika Rossini (2018)
p53 modeling as a route to mesothelioma patients stratification and novel therapeutic identification
K. Tian (2018)
Assessment of signaling pathway inhibitors and identification of predictive biomarkers in malignant pleural mesothelioma.
R. Tranchant (2018)
Pemetrexed-loaded nanoparticles targeted to malignant pleural mesothelioma cells: an in vitro study
E. Cova (2019)
Semantic Scholar Logo Some data provided by SemanticScholar