Trial reportInvestigational new drugs2014
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.
Trial report in Investigational new drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01620970 (Phase II Study of the Fully Human Monoclonal Antibody Against Transforming Growth Factor-beta), which is not on this map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase II Study of the Fully Human Monoclonal Antibody Against Transforming Growth Factor-beta (TGFβ) Receptor ALK1 (PF-03446962) in Relapsed or Refractory Urothelial Cancer (UC) Failing First-line Treatment.
Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- Combination of GT90001 and nivolumab in patients with advanced hepatocellular carcinoma: a multicenter, single-arm, phase 1b/2 study.BMC medicine · 2023Trial
- A stochastically curtailed two-arm randomised phase II trial design for binary outcomes.Pharmaceutical statistics · 2021Trial
- Targeting Tumor-Associated Macrophages and Cancer-Associated Fibroblasts to Overcome Therapeutic Resistance in Hepatocellular Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Targeting inflammation as cancer therapy.Journal of hematology & oncology · 2024Review
- Article
- Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies.Journal of translational medicine · 2023Review
- Assessing suffering of patients on cancer treatment and of those no longer treated using ESAS-Total Care (TC).Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2023Article
- Targeted Therapy for Cancers: From Ongoing Clinical Trials to FDA-Approved Drugs.International journal of molecular sciences · 2023Review
- TGF-β Signaling in Progression of Oral Cancer.International journal of molecular sciences · 2023Review
- Molecular Pathways and Mechanisms of TGFβ in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Article
- A stochastically curtailed single-arm phase II trial design for binary outcomes.Journal of biopharmaceutical statistics · 2022Article
- Bone Morphogenetic Protein Signaling in Cancer; Some Topics in the Recent 10 Years.Frontiers in cell and developmental biology · 2022Review
- Tumor promoting roles of IL-10, TGF-β, IL-4, and IL-35: Its implications in cancer immunotherapy.SAGE open medicine · 2022Review
- Targeting cancer associated fibroblasts to enhance immunotherapy: emerging strategies and future perspectives.Oncotarget · 2021Article
- Tumor microenvironment as a therapeutic target in cancer.Pharmacology & therapeutics · 2021Review
- A phase Ib study of the combination regorafenib with PF-03446962 in patients with refractory metastatic colorectal cancer (REGAL-1 trial).Cancer chemotherapy and pharmacology · 2019Article
- Combined Inhibition of DYRK1A, SMAD, and Trithorax Pathways Synergizes to Induce Robust Replication in Adult Human Beta Cells.Cell metabolism · 2019Article
- Therapeutic targeting of the crosstalk between cancer-associated fibroblasts and cancer stem cells.American journal of cancer research · 2019Review
- Bone morphogenetic protein receptor signal transduction in human disease.The Journal of pathology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.