Ficlatuzumab plus chemo shows early promise in refractory AML

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By Megan Brooks

NEW YORK (Reuters Health) - The combination of ficlatuzumab plus chemotherapy showed considerable early promise in relapsed/refractory acute myeloid leukemia (AML) in a small phase-1 study.

"The high rate of complete remissions was surprising to us," Dr. Charalambos Andreadis of the University of California, San Francisco, told Reuters Health by email. "These are all patients who were refractory to their initial treatment. Single-agent chemotherapy, the cytarabine used here, does not produce such high response rates in that setting."

Ficlatuzumab is an investigational, first-in-class monoclonal antibody that binds to extracellular hepatocyte growth factor (HGF) to prevent it from activating MET signaling and stimulating tumor growth.

What's "exciting" about this study, said Dr. Andreadis, "is that it's the first time that we targeted a molecule outside of the cancer cell, i.e. HGF. All of the leukemia treatments to date focus on the internal environment of the cell, whether that is DNA, the replication machinery, or mutant proteins. This is the first time that a molecule working outside the cell and possibly serving as a means of communication with its environment has shown potential activity."

The study is published in Blood Cancer Discovery, a journal of the American Association for Cancer Research.

Participants included 17 adults with AML that was either refractory to prior treatment or that had relapsed within 12 months of prior treatment. The patients received four doses of ficlatuzumab, administered 14 days apart, along with the chemotherapeutic cytarabine.

Nine of 17 patients (53%) had a complete response, which is "quite favorable" when compared with a complete response rate in the 30% range with standard treatment, the researchers say in their paper.

In 16 patients, minimal residual disease (MRD) status was assessed and four of the nine responders were MRD negative.

Among responders at the time of censoring, median progression-free survival was 31.2 months, with overall survival not yet reached.

Ten patients (eight responders and two non-responders) went on to allogeneic hematopoietic-cell transplantation and six of these patients were still in remission at the most recent follow-up.

Febrile neutropenia was the most common adverse event with the ficlatuzumab/cytarabine combination. Serious adverse events occurred in two patients, and there was one death deemed unrelated to the investigational therapy.

This small phase-1 study demonstrates that ficlatuzumab can be safely combined with cytarabine in this patient population, Dr. Andreadis told Reuters Health.

"As such, it proved that the combination is well tolerated and offered a hint of significant disease activity. It will need to be confirmed in a larger future study," he added.

"We also identified some very significant perturbations in the internal signaling pathways of blood cells in response to this treatment that will need to be validated with subsequent experiments," Dr. Andreadis said.

He gave a shoutout to Dr. Victoria Wang at UCSF and Dr. Brad Blaser with The Ohio State University Comprehensive Cancer Center who "conceived the trial and ran all of the very elegant analyses."

The team is working with the company that produces ficlatuzumab, AVEO Oncology, to design a larger study to test this combination against a currently used therapy.

The current study did not have commercial support. The authors reported no ties to AVEO during the conduct of the study.

SOURCE: https://bit.ly/36HwBU5 Blood Cancer Discovery, online July 16, 2021.

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