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|Ref Type||Journal Article|
|Authors||Goff LW, Cohen RB, Berlin JD, de Braud FG, Lyshchik A, Noberasco C, Bertolini F, Carpentieri M, Stampino CG, Abbattista A, Wang E, Borghaei H|
|Title||A Phase I Study of the Anti-Activin Receptor-Like Kinase 1 (ALK-1) Monoclonal Antibody PF-03446962 in Patients with Advanced Solid Tumors.|
|Journal||Clinical cancer research : an official journal of the American Association for Cancer Research|
|Date||2016 May 01|
|Abstract Text||Objectives of this dose-finding study were to determine the MTD and recommended phase II dose (RP2D) of the first-in-class anti-activin receptor-like kinase 1 (ALK-1) monoclonal antibody PF-03446962, and assess safety and antitumor activity in patients with advanced solid tumors.This open-label, multicenter study was based on a 3+3 design. PF-03446962 was administered biweekly by intravenous infusion, at doses ranging from 0.5 to 15 mg/kg.Forty-four patients received treatment with PF-03446962. Dose-limiting toxicities observed during dose escalation included grade 3 increased amylase, grade 3/4 increased lipase, and grade 3/4 thrombocytopenia. The MTD was determined to be 10 mg/kg. The RP2D was set at 7 mg/kg for patients with advanced solid tumors, based on the observed safety, pharmacokinetics, and antitumor activity. The most-frequent treatment-related, all-grade adverse events included thrombocytopenia (20.5%), fatigue (15.9%), and nausea, increased amylase, and increased lipase (each 11.4%). Treatment-related telangiectasia was noted in 7% of patients, suggesting in vivo inhibition of the ALK-1 pathway. None of the deaths was deemed to be treatment-related. Three (6.8%) patients with advanced hepatocellular carcinoma, renal cell carcinoma, or non-small cell lung cancer achieved a partial response, and 12 (27.3%) patients had stable disease, across dose levels. Contrast-enhanced ultrasound analysis of tumor vascularity showed reduction in tumor perfusion in 2 patients with stable disease following treatment with PF-03446962.The clinical activity demonstrated in this study points to PF-03446962 as a novel approach to antiangiogenic therapy, with manageable safety profile and single-agent, antitumor activity in patients with advanced solid tumors. Clin Cancer Res; 22(9); 2146-54. ©2015 AACR.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|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||lung non-small cell carcinoma||not applicable||Ascrinvacumab||Phase I||Actionable||In a Phase I trial, a patient with non-small cell lung carcinoma demonstrated a partial response for 308 days when treated with PF-03446962 (PMID: 26655846).||26655846|
|Unknown unknown||clear cell renal cell carcinoma||not applicable||Ascrinvacumab||Phase I||Actionable||In a Phase I trial, a patient with renal clear cell carcinoma demonstrated a partial response for 325 days when treated with PF-03446962 (PMID: 26655846).||26655846|
|Unknown unknown||Advanced Solid Tumor||not applicable||Ascrinvacumab||Phase I||Actionable||In a Phase I trial, PF-03446962 treatment was deemed safe and resulted in anti-tumor activity in patients with advanced solid tumors, demonstrating a partial response in 6.8% (3/44) and stable disease in 27.3% (12/44) (PMID: 26655846).||detail... 26655846|
|Unknown unknown||hepatocellular carcinoma||not applicable||Ascrinvacumab||Phase I||Actionable||In a Phase I trial, a patient with hepatocellular carcinoma demonstrated a partial response for 44 days when treated with PF-03446962 (PMID: 26655846).||26655846|