Rare Disease Report

New AML Drug Shows Promise in Phase I Trial

JUNE 13, 2016
Ruth J Hickman, MD
Interim results are promising in a phase I trial of vadastuximab talirine used in combination with hypomethylating agents. In patients with acute myeloid leukemia (AML), the combination has shown a high response rate, good tolerability, and low early mortality. The drug’s developer, Seattle Genetics, shared the data during an oral presentation at the 21st Congress of the European Hematology Association (EHA) that took place in Copenhagen, Denmark, June 9-12.

About AML

AML arises from the myeloid cells that serve as precursors to other types of blood cells. These cancer cells originate in the bone marrow and quickly spread through the bloodstream. The cancer cells crowd out normal blood cell cells, leading to reduced number of red blood cells, white blood cells, and platelets. This causes symptoms like fatigue, increased risk of infection, and bleeding.
Without treatment, the aggressive cancer progresses rapidly. Many patients receive intensive chemotherapy to kill the cancerous blood cells and a later stem cell transplant from a donor. Many patients respond to this initially, but relapse is common.
Younger patients do better with this therapy, but over half of patients with AML are over the age of 65. Many older people cannot tolerate the side effects of these intensive treatments. Drugs called hypomethylating agents (HMAs) provide the standard treatment for these patients, who typically do not survive longer than 10 months. Treatments for AML have not changed substantially in the last 30 years.

A new treatment approach to AML

Vadastuximab talirine (SGN-CD33A; 33A) approaches AML from a different angle. It is an antibody-drug conjugate. This type of treatment has revolutionized treatment in other cancer fields. These drugs can often be more effective because they bind selectively to cancer cells, and so have decreased side effects compared to general chemotherapy. vadastuximab talirine binds to the CD-33A receptor that is found on most AML cancer cells. The drug delivers a powerful anti-tumor drug, pyrrolobenzodiazepine, directly into these cells. Both the FDA and the European Commission have granted vadastuximab talirine an orphan drug designation.

Presented data

Amir Fathi, MD, Assistant Professor of Medicine at Harvard Medical School shared the data at the EHA meeting. He presented interim results from the 53 patients in the ongoing phase 1 study.
All patients were unable to tolerate, or had declined, intensive standard chemotherapy treatment. Median patient age was 75. Patients received vadastuximab talirine and an HMA (either azacitidine or decitabine).
The overall response rate was 76%. Almost as many, 71%, had either complete remission or complete remission with some remaining decreased levels of platelets or white blood cells. This rate was very similar in the azacitidine and decitabine groups (71% compared to 72%). Higher risk patients also responded well.
The estimated median overall survival for the first 25 patients in the study was 12.75 months. Median relapse-free survival was 7.7 months.
The most common adverse events were fatigue (57%), low platelets (53%), nausea (49%), low white blood count with fever (45%), constipation (42%), and anemia (42%).
“There is a dire need to improve outcomes for patients with AML,” said Dr Fathi. “The antileukemic activity we have observed in the phase 1 clinical trial evaluating 33A (vadastuximab talirine) combination therapy in AML patients continues to be encouraging. This is an incredibly difficult disease to treat, and the results to-date continue to show a balance of activity and tolerability together with low early mortality rates.”
In a press release, Jonathan Drachman, MD, Chief Medical Officer at Seattle Genetics, noted, “We believe that adding 33A (vadastuximab talirine) to HMAs may improve efficacy and has the potential to redefine the treatment of AML.”

Based on these data, Seattle Genetics is now enrolling patients for a  phase 3 clinical trial, CASCADE. This trial will study vadastuximab talirine in combination with HMAs in previously untreated AML patients who are not well enough for standard intensive chemotherapy.

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