On April 1, 2019 AVEO Oncology (NASDAQ:AVEO) and Biodesix, Inc. reported results from an investigator-sponsored Phase Ib expansion cohort of ficlatuzumab, AVEO’s potent hepatocyte growth factor (HGF) inhibitory antibody product candidate, in combination with cytarabine in patients with relapsed and refractory acute myeloid leukemia (AML) (Press release, AVEO, APR 1, 2019, View Source [SID1234534855]). The results were presented in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2019 Annual Meeting. The presentation, titled, "CyFi: Results from a phase Ib expansion cohort of ficlatuzumab (Fi) combined with high-dose cytarabine (Cy) in patients with high risk relapsed or refractory acute myeloid leukemia (AML)" (abstract CT078/2) is available in the Publications & Presentations section of AVEO’s website.
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Elevated serum HGF level is an adverse prognostic factor associated with worse survival in AML and other cancers. Pre-clinical models have shown that myeloid blasts produce HGF and that blocking the HGF/c-Met pathway sensitizes blasts to cell death. The Phase Ib trial, which was funded by Gateway for Cancer Research and is being conducted at the UCSF Medical Center under the direction of Charalambos Andreadis, M.D., Associate Professor of Clinical Medicine, Director, Clinical Research Support Office, UCSF Helen Diller Family Comprehensive Cancer Center, was designed to assess the safety, tolerability and preliminary efficacy of ficlatuzumab with cytarabine in AML patients who are refractory to first line therapy (7+3) or have relapsed within one year of induction, a population known to have poor outcomes.
The maximally tolerated dose was 20 mg/kg of ficlatuzumab on day 1 followed by 2 g/m2 cytarabine daily on days 2-7. Of 12 patients who received ficlatuzumab and cytarabine at the maximally tolerated dose, one of whom was non-evaluable, 6 achieved a complete response (CR). Of 18 patients enrolled in the study, 17 were evaluable and 9 achieved a CR. The most frequent grade 3/4 treatment emergent adverse events observed were febrile neutropenia, LFT abnormalities, and electrolyte disturbance. There was one death from sepsis and multi-organ failure that was determined to be disease related, and one patient withdrew from the study due to grade 4 gastrointestinal bleed, determined to be likely ficlatuzumab related. scRNA sequencing identified a TNF alpha and IFN gamma inflammatory signature that correlated with response to ficlatuzumab at count recovery.
"Patients with AML who are refractory to induction therapy or relapse within one year have poor outcomes," said Dr. Andreadis. "Elevated serum HGF level is an adverse prognostic factor, and these results demonstrate that the anti-HGF antibody ficlatuzumab combined with cytarabine holds potential to affect outcomes in patients with relapsed or refractory AML. We look forward to potentially evaluating ficlatuzumab in larger outcome studies in AML."
"In addition to an attractive tolerability profile observed to date, we also see the potential to identify biomarkers of response using RNA sequencing. In light of these data, we believe that further evaluation in this patient population is warranted, and we look forward to considering additional studies with our partners at Biodesix as a potential next step for the program," said Michael Bailey, president and chief executive officer of AVEO.
"We look forward to supporting ficlatuzumab’s biomarker development initiatives with a broad set of diagnostic technologies," said Paul Beresford, chief business officer of Biodesix.
About Ficlatuzumab
Ficlatuzumab (formerly known as AV-299) is a potent hepatocyte growth factor (HGF) inhibitory antibody that binds to the HGF ligand with high affinity and specificity to inhibit HGF/c-Met biological activities. AVEO and Biodesix, Inc. have a worldwide agreement to develop and commercialize ficlatuzumab. Ficlatuzumab is currently being evaluated in investigator-sponsored trials in squamous cell carcinoma of the head and neck (HNSCC), metastatic pancreatic ductal cancer (PDAC), and acute myeloid leukemia (AML).