Trial reportCancer chemotherapy and pharmacology2014
A first-in-human study of the anti-α5β1 integrin monoclonal antibody PF-04605412 administered intravenously to patients with advanced solid tumors.
Trial report in Cancer chemotherapy and pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Integrin α5β1 in pancreatic ductal adenocarcinoma: Tumour‒stroma crosstalk, hypoxia and therapeutic targeting.Clinical and translational medicine · 2026Review
- Allosteric regulation of fibronectin binding by the anti-β1 integrin antibody TS2/16.PNAS nexus · 2026Article
- Alpha 5 integrin as a prognostic biomarker for survival in carcinomas: a systematic review.Discover oncology · 2025Review
- Role and mechanism of Integrin α5β1 in bone formation and disease.Frontiers in cell and developmental biology · 2025Review
- Integrin β1 in breast cancer: mechanisms of progression and therapy.Breast cancer (Tokyo, Japan) · 2025Review
- Cadherins, Selectins, and Integrins in CAM-DR in Leukemia.Frontiers in oncology · 2020Review
- Fibronectin in malignancy: Cancer-specific alterations, protumoral effects, and therapeutic implications.Seminars in oncology · 2019Review
- Review
- Shedding New Light on The Role of ανβ3 and α5β1 Integrins in Rheumatoid Arthritis.Molecules (Basel, Switzerland) · 2019Review
- Stromal fibronectin expression in patients with resected pancreatic ductal adenocarcinoma.World journal of surgical oncology · 2019Article
- The functional role of integrins during intra- and extravasation within the metastatic cascade.Molecular cancer · 2019Review
- Integrins as therapeutic targets in the organ-specific metastasis of human malignant melanoma.Journal of experimental & clinical cancer research : CR · 2018Review
- Article
- Interest of integrins targeting in glioblastoma according to tumor heterogeneity and cancer stem cell paradigm: an update.Oncotarget · 2017Review
- Integrins in the Spotlight of Cancer.International journal of molecular sciences · 2016Review
- Tension in Cancer.International journal of molecular sciences · 2016Review
- Matrix control of pancreatic cancer: New insights into fibronectin signaling.Cancer letters · 2016Review
- Ligand-induced Epitope Masking: DISSOCIATION OF INTEGRIN α5β1-FIBRONECTIN COMPLEXES ONLY BY MONOCLONAL ANTIBODIES WITH AN ALLOSTERIC MODE OF ACTION.The Journal of biological chemistry · 2016Article
- Integr(at)in(g) EGFR therapy in HNSCC.Annals of translational medicine · 2015Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeA first-in-human clinical trial of a fully human, Fc-engineered IgG1 monoclonal antibody targeting integrin α5β1 was conducted to evaluate tolerability, maximum tolerated dose, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity.
methodsEscalating doses of PF-04605412 were given IV on day 1, 28 and every 2 weeks thereafter to patients with advanced solid tumors until disease progression or unacceptable toxicity. Sequential dose cohorts were evaluated based on a modified 3 + 3 dose-escalation design. The starting dose was 7.5 mg based on preclinical data.
resultsThirty-three patients were enrolled to six dose levels (7.5, 11.25, 16.9, 34, 68 and 136 mg). Twenty-three patients were evaluable for the primary endpoint (determination of the maximum tolerated dose). Five patients required permanent drug discontinuation due to acute infusion-related reactions, which occurred as grade 3 events in two patients. PK analysis indicated that the targeted drug exposure based on preclinical models was not achieved by the tolerated doses and PK modeling suggesting that doses at least fivefold higher would be necessary. No anti-tumor activity was observed.
conclusionBased on the safety data, the risks associated with the likelihood of significant cytokine-mediated infusion reactions at higher doses, the projected high dose necessary to affect on the biological target and the lack of anti-tumor activity at the doses explored, the trial was prematurely terminated without determining a formal maximum tolerated dose. Further clinical development of PF-04605412 has been discontinued.
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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.