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

A Phase II Study Of PF‐03446962 In Patients With Advanced Malignant Pleural Mesothelioma. CCTG Trial IND.207

P. Wheatley-Price, Q. Chu, M. Bonomi, J. Seely, A. Gupta, G. Goss, J. Hilton, R. Feld, C. Lee, J. Goffin, A. Maksymiuk, N. Murray, L. Hagerman, P. Bradbury
Published 2016 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
&NA; There is no approved second‐line systemic therapy option for malignant pleural mesothelioma (MPM), but targeting angiogenesis is an area of investigation. PF‐03446962 is a fully human antibody against activin receptor‐like kinase 1, which is commonly expressed in tumor vasculature. We performed a multicenter, open label, single‐arm, two‐stage phase II study of PF‐03446962 in patients with MPM and progressive disease after platinum‐based chemotherapy. In total, 17 patients were enrolled, but no partial or complete responses were observed. The trial did not meet the prespecified response criterion for moving to the second stage. There were only three grade 3 (G3) or higher nonhematological toxicities observed (G3 hypertension [n=2] and G3 fatigue [n=1]) and just one episode of G3 lymphopenia. In conclusion, PF‐03446962, despite being generally well tolerated, failed to demonstrate efficacy in the treatment of advanced MPM as a single agent. There are no plans for further investigation of this agent in MPM.
This paper references
Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: combating tumor evasion of antiangiogenic therapy.
Saul J. Priceman (2010)
Expression of angiogenesis‐related gene profiles and development of resistance to tyrosine‐kinase inhibitor in advanced renal cell carcinoma: Characterization of sorafenib‐resistant cells derived from a cutaneous metastasis
T. Karashima (2013)
VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours
Y. Ohta (1999)
Expression of vascular endothelial growth factor in diffuse malignant pleural mesothelioma
J. König (1999)
Targeting activin receptor-like kinase 1 inhibits angiogenesis and tumorigenesis through a mechanism of action complementary to anti-VEGF therapies.
Dana D. Hu-Lowe (2011)
Anti-PlGF Inhibits Growth of VEGF(R)-Inhibitor-Resistant Tumors without Affecting Healthy Vessels
Christian Fischer (2007)
Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada.
J. Van Meerbeeck (2005)
Anti-FGF2 approaches as a strategy to compensate resistance to anti-VEGF therapy: long-pentraxin 3 as a novel antiangiogenic FGF2-antagonist.
P. Alessi (2009)
Immunological effects of the TGFβ-blocking antibody GC1008 in malignant pleural mesothelioma patients
J. Stevenson (2013)
Second line therapy in malignant pleural mesothelioma: A systematic review.
W. Buikhuisen (2015)
Acquired drug resistance to vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor in human vascular endothelial cells.
T. Arao (2011)
Prognosis and prognostic factors of patients with mesothelioma: a population-based study
S. van der Bij (2012)
A Phase I Study of the Anti-Activin Receptor-Like Kinase 1 (ALK-1) Monoclonal Antibody PF-03446962 in Patients with Advanced Solid Tumors
L. Goff (2015)
Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.
N. Vogelzang (2003)
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)

This paper is referenced by
Unmasking carcinoma-associated fibroblasts: Key transformation player within the tumor microenvironment.
Q. Meng (2020)
A systematic review and meta-analysis of second-line therapies for treatment of mesothelioma.
F. Petrelli (2018)
Repurposing Quinacrine for Treatment of Malignant Mesothelioma: In-Vitro Therapeutic and Mechanistic Evaluation
N. Kulkarni (2020)
ALK1 : une nouvelle voie de signalisation dans le développement vasculaire physiologique et tumoral
Marie Ouarné (2017)
Therapeutic implications of cancer epithelial-mesenchymal transition (EMT)
E. Cho (2019)
Clinical development of therapies targeting TGFβ: current knowledge and future perspectives.
D. Ciardiello (2020)
ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma.
I. Opitz (2020)
PIM1 knockdown inhibits cell proliferation and invasion of mesothelioma cells.
A. S. Mawas (2017)
Growth factor signaling in the breast tumor microenvironment
Matteo Bocci (2018)
Antisense Oligonucleotides Targeting Angiogenic Factors as Potential Cancer Therapeutics
Bao T. Le (2019)
Bone marrow niche crosses paths with BMPs: a road to protection and persistence in CML.
Caroline Busch (2019)
A phase Ib study of the combination regorafenib with PF-03446962 in patients with refractory metastatic colorectal cancer (REGAL-1 trial)
J. Clarke (2019)
Reduced activin receptor-like kinase 1 activity promotes cardiac fibrosis in heart failure.
Kevin J. Morine (2017)
Malignant Pleural Mesothelioma: Is Tailoring the Second-Line Therapy Really “Raising the Bar?”
V. Noia (2019)
Safer approaches to therapeutic modulation of TGF‐&bgr; signaling for respiratory disease
Philippe Lachapelle (2018)
ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma
A. Scherpereel (2020)
BMP9, but not BMP10, acts as a quiescence factor on tumor growth, vessel normalization and metastasis in a mouse model of breast cancer
Marie Ouarné (2018)
Transforming growth factor β signaling pathway: A promising therapeutic target for cancer
Y. Chen (2019)
Tumor angiogenesis revisited: Regulators and clinical implications
R. Ronca (2017)
Semantic Scholar Logo Some data provided by SemanticScholar