Immuno-Oncology Resource Center

Immuno-Oncology Resource Center

Perspective from Jonathan M. Gerber, MD, PhD
Source:

Wang VE, et al. Blood Cancer Discov. 2021;doi:10.1158/2643-3230.BCD-21-0055.

Disclosures: Blaser reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
July 22, 2021
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Ficlatuzumab plus chemotherapy effective in relapsed or refractory acute myeloid leukemia

Perspective from Jonathan M. Gerber, MD, PhD
Source:

Wang VE, et al. Blood Cancer Discov. 2021;doi:10.1158/2643-3230.BCD-21-0055.

Disclosures: Blaser reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Ficlatuzumab plus single-agent chemotherapy showed encouraging efficacy and appeared safe among patients with relapsed or refractory acute myeloid leukemia, according to phase 1 study results published in Blood Cancer Discovery.

“Patients with relapsed or refractory AML have poor outcomes, with response rates of between 30% and 40% to intensive salvage chemotherapy. Durable complete responses are even more uncommon,” Bradley W. Blaser, MD, PhD, assistant professor of leukemia research at The Ohio State University Comprehensive Cancer Center, told Healio. “Ficlatuzumab could be a promising option for patients with relapsed or refractory AML, particularly those lacking targetable mutations, but larger randomized studies will need to confirm this.”

Ficlatuzumab plus single-agent chemotherapy showed encouraging efficacy and appeared safe among patients with relapsed or refractory acute myeloid leukemia.
Data were derived from Wang VE, et al. Blood Cancer Discov. 2021;doi:10.1158/2643-3230.BCD-21-0055.

Ficlatuzumab (Aveo Oncology) is an investigational, first-in-class monoclonal antibody that binds the extracellular hepatocyte growth factor (HGF) to prevent activation of MET signaling and stimulation of tumor growth.

Blaser and colleagues assessed the safety and efficacy of a four-dose regimen of 20 mg/kg ficlatuzumab given 14 days apart in combination with high-dose cytarabine in a cohort of 17 patients (median age, 58 years; 58.8% men) with AML who were either refractory to or had relapsed within 1 year of previous therapy.

Thirteen patients had de novo AML, three had secondary AML and one had myelodysplastic syndrome, refractory anemia with excess blasts category 2 (RAEB-2). In addition, 41.2% of patients exhibited a complex karyotype and 23.5% harbored 5q deletion. Safety and maximum tolerated dose of the combination served as primary objectives. Secondary objectives included the rate of complete remission, PFS and OS.

Researchers assessed response through next-generation sequencing with the ARUP Myeloid Malignancies Mutation panel and minimal residual disease using the University of Washington multiparameter flow cytometry assay.

Results showed the ficlatuzumab-chemotherapy combination induced an overall response rate of 53%, with all responders experiencing complete remission and four having no signs of minimal residual disease.

Median PFS was 6.6 months (31.2 months among responders) and median OS was 18.1 months (not reached among responders). Eight responders and two nonresponders underwent hematopoietic stem cell transplantation, of whom six remained in remission at last follow-up.

The combination also appeared safe. Febrile neutropenia was the most common adverse event, with nine patients experiencing grade 3 or greater febrile neutropenia. Two patients experienced serious adverse events. One patient death occurred that was unrelated to the combination treatment.

Researchers additionally examined peripheral blood mononuclear cells pooled at baseline and at various other timepoints during the study. Results confirmed on-target inhibition of HGF, with ficlatuzumab leading to attenuation of phosphorylation of MET.

Bradley W. Blaser, MD, PhD
Bradley W. Blaser

“High-dimensional correlative studies with mass cytometry and single-cell RNA sequencing associated response to ficlatuzumab with induction of genes involved in leukocyte activation,” Bradley said. “Resistance to ficlatuzumab was associated with expression of genes involved in protein translation, cell adhesion and type 1 interferon signaling. Prospective clinical studies benefit from high-dimensional correlative science for identifying biomarkers of response and resistance. Genetic multiplexing, as performed here, is one way to reduce cost and increase sample throughput in this type of study.”

Ficlatuzumab could be a treatment option for patients with relapsed or refractory AML if larger randomized studies confirm its efficacy, according to Bradley.

“In correlative studies, resistance to ficlatuzumab was associated with pathways known to be important in leukemia biology,” Bradley said. “These data provide hypotheses for the lab and for future clinical trials. A phase 2 clinical study has been initiated based on these findings, and work aimed at understanding mechanisms of resistance to anti-HGF therapy is ongoing in the lab.”

For more information:

Bradley W. Blaser, MD, PhD, can be reached at The Ohio State University Comprehensive Cancer Center, 460 W. 10th Ave., Columbus, OH 43210; email: bradley.blaser@osumc.edu.