Novel Monoclonal Antibody and Chemotherapy Combination Under Study in Resistant AML
Posted: Friday, August 13, 2021
Charalambos Andreadis, MD, of the Helen Diller Comprehensive Cancer Center, University of California, San Francisco, and colleagues conducted a study to examine the investigational agent ficlatuzumab—a first-in-class monoclonal antibody that prevents MET signaling and tumor growth by binding to the extracellular hepatocyte growth factor—in combination with cytarabine for refractory acute myeloid leukemia (AML). Their results, published in Blood Cancer Discovery, showed “promising clinical activity” with an acceptable safety profile.
“The 53% response rate was quite striking to us, since historical response rates for the standard-of-care treatment are in the 30% range,” stated Dr. Andreadis in an American Association for Cancer Research press release. “While these results need to be validated in a larger study, they suggest that ficlatuzumab in combination with single-agent chemotherapy may lead to better responses with less toxicity in patients with relapsed/refractory AML.”
This phase I trial focused on 17 patients with relapsed or refractory AML who were administered ficlatuzumab. It was given in doses of 5 mg/kg, 10 mg/kg, 15 mg/kg, or 20mg/kg, once every 2 weeks up to 4 doses, along with five doses of 2 g/m2 of cytarabine chemotherapy.
A majority of patients (11 of 17) completed all doses of ficlatuzumab, and a complete response was observed in 9 patients, with 4 exhibiting no signs of minimal residual disease. Despite having no delay in therapy administration, 6 patients missed a total of 11 doses and discontinued treatment due to disease progression (n = 3), starting consolidation (n = 1), sepsis (n = 1), or upper gastrointestinal bleeding (n = 1).
Although overall survival was not reached, the progression-free survival was 31.2 months. Additionally, three patients who responded received three more doses of ficlatuzumab during consolidation. The most common grade 3 or higher adverse event was febrile neutropenia, affecting nine patients, followed by sepsis (n = 3), ulceration and esophagitis, gastrointestinal bleeding, and hypotension (n = 2).
Disclosure: For full disclosures of the study authors, visit bloodcancerdiscov.aacrjournals.org.