| Title |
PF-03446962, a fully-human monoclonal antibody against transforming growth-factor β (TGFβ) receptor ALK1, in pre-treated patients with urothelial cancer: an open label, single-group, phase 2 trial
|
|---|---|
| Published in |
Investigational New Drugs, February 2014
|
| DOI | 10.1007/s10637-014-0074-9 |
| Pubmed ID | |
| Authors |
A. Necchi, P. Giannatempo, L. Mariani, E. Farè, D. Raggi, M. Pennati, N. Zaffaroni, F. Crippa, A. Marchianò, N. Nicolai, M. Maffezzini, E. Togliardi, M. G. Daidone, A. M. Gianni, R. Salvioni, F. De Braud |
| Abstract |
Despite a compelling preclinical rationale for the use of anti-angiogenic drugs in urothelial cancer (UC), short-living responses have been observed in clinical trials. PF-03446962 is a novel monoclonal antibody against Activin Receptor-Like Kinase-1 (ALK1), a type I subclass of the TGFβ receptor, with dose-dependent anti-angiogenic activity. An open label, single-group, phase 2 trial of PF-03446962 was conducted in salvage setting. Patients failing at least one chemotherapy regimen were eligible. Design provided PF-03446962 10 mg/Kg intravenously fortnightly until disease progression (PD) or unacceptable toxicity. Two-month progression-free survival (PFS) was the primary endpoint. The trial was registered with ClinicalTrials.gov, number NCT01620970. Fourteen patients were enrolled from October 2012 to July 2013. Median age was 64 years (interquartile range [IQR]: 58.2-69.5), 9 patients had a Bellmunt score of 1-2, median number of prior drugs was 3. One stable disease and 13 PD were recorded and the study met the futility stopping rule of interim analysis. Median PFS was 1.8 months (95 %CI, 1.4-2.0). After a median follow up of 7.4 months (IQR 4.5-10.9), 8 patients are alive. Median overall survival (OS) was 8 months (95 %CI, 2.9-not estimable). Most common toxicities were thrombocytopenia (G1-2 in 5 cases, persistent G3 in one, with 3 dose delays and 1 dose interruption), fatigue and abdominal pain (G1-2 in 4 cases each). Impairment of quality of life (ESAS score) was observed as well as an increase from baseline to +2 month median levels of vascular endothelial growth factor (VEGF) and interleukin-8. PF-03446962 had no activity as single drug in refractory UC and we do not recommend further investigation outside of the combination with agents targeting the VEGF receptor axis. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Italy | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 39 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 9 | 23% |
| Student > Master | 8 | 21% |
| Student > Ph. D. Student | 7 | 18% |
| Student > Bachelor | 2 | 5% |
| Professor | 2 | 5% |
| Other | 4 | 10% |
| Unknown | 7 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 21% |
| Biochemistry, Genetics and Molecular Biology | 7 | 18% |
| Agricultural and Biological Sciences | 4 | 10% |
| Nursing and Health Professions | 3 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
| Other | 8 | 21% |
| Unknown | 7 | 18% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 March 2022.
All research outputs
#4,665,912
of 23,390,392 outputs
Outputs from Investigational New Drugs
#161
of 1,190 outputs
Outputs of similar age
#45,548
of 222,471 outputs
Outputs of similar age from Investigational New Drugs
#2
of 13 outputs
Altmetric has tracked 23,390,392 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,190 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done well, scoring higher than 86% of its peers.
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We're also able to compare this research output to 13 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.