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Ref Type Journal Article
PMID (21447719)
Authors Rudman SM, Jameson MB, McKeage MJ, Savage P, Jodrell DI, Harries M, Acton G, Erlandsson F, Spicer JF
Title A phase 1 study of AS1409, a novel antibody-cytokine fusion protein, in patients with malignant melanoma or renal cell carcinoma.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 17
Issue 7
Date 2011 Apr 01
Abstract Text AS1409 is a fusion protein comprising a humanized antibody BC1 linked to interleukin-12 (IL-12). It is designed to deliver IL-12 to tumor-associated vasculature using an antibody targeting the ED-B variant of fibronectin.We conducted a phase 1 trial of weekly infusional AS1409 in renal carcinoma and malignant melanoma patients. Safety, efficacy, markers of IL-12-mediated immune response, and pharmacokinetics were evaluated.A total of 11 melanoma and 2 renal cell carcinoma patients were treated. Doses of 15 and 25 μg/kg were studied. Most drug-related adverse events were grade 2 or less, and included pyrexia, fatigue, chills, headache, vomiting, and transient liver function abnormalities. Three dose limiting toxicities of grade 3 fatigue and transaminase elevation were seen at 25 μg/kg. IFN-γ and interferon-inducible protein-10 (IP-10) were elevated in all patients, indicating activation of cell-mediated immune response; this was attenuated at subsequent cycles. Antidrug antibody responses were seen in all patients, although bioassays indicate these do not neutralize AS1409 activity. Plasma half-life was 22 hours and not dose-dependent. Five patients received 6 cycles or more and a best response of at least stable disease was seen in 6 (46%) patients. Partial response was seen in a melanoma patient, and disease shrinkage associated with metabolic response was maintained beyond 12 months in another melanoma patient despite previous rapid progression.The maximum tolerated dose was established at 15 μg/kg weekly. AS1409 is well tolerated at this dose. Evidence of efficacy assessed by RECIST, functional imaging, and biomarker response warrants the planned further investigation using this dose and schedule in malignant melanoma.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
AS1409 AS1409 2 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
AS1409 AS1409 is a fusion protein comprising BC1 and interleukin-12 (IL-12), which allows recognition of the extra-domain B(ED-B) fibronectin isoform present in tumor cells and directly delivers IL-12 to the tumor thereby stimulating an immunological response (PMID: 21447719).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown renal cell carcinoma not applicable AS1409 Phase I Actionable In a Phase I trial, AS1409 treatment in patients with either melanoma or renal cell carcinoma resulted in stable disease in 46% (6/13) of patients (PMID: 21447719). 21447719
Unknown unknown melanoma not applicable AS1409 Phase I Actionable In a Phase I trial, AS1409 treatment in patients with either melanoma or renal cell carcinoma resulted in stable disease in 46% (6/13) of patients and in two patients with melanoma, one demonstrated a partial response while another showed tumor shrinkage, which lasted beyond 12 months (PMID: 21447719). 21447719