FDA Clears IND Application for Refractory AML Combination Therapy

The Medical College of Wisconsin has received clearance from the U.S. Food and Drug Administration (FDA) for the previously unannounced Investigational New Drug (IND) application for the Phase 1 trial of a combination therapy for relapsed or refractory acute myeloid leukemia (AML).

Actimab-A is being developed by Actinium Pharmaceuticals, Inc., and the trial will investigate it in combination with CLAG-M. Dr Sameem Abedin will lead in collaboration with Dr Ehab Atallah. The trial will enroll up to 18 patients and will assess both safety and efficacy based on response rates, percentage of patients receiving a bone marrow transplant and overall survival (OS).

The combination trial expands the addressable patient population for Actinium's CD33 program into relapsed or refractory patients suitable for chemotherapy. The drug has previously been evaluated in patients with AML who are over the age of 60 and unfit for intense chemotherapy.

“The use of our actinium-225 — anti-CD33 ARC in combination with cytotoxic therapies such as CLAG-M has the potential to improve outcomes for a significant number of patients,” said Dr. Mark Berger, Actinium’s Chief Medical Officer in a press release. “We believe our ARC approach, which has shown to be potent while having minimal extramedullary toxicities in over 100 patients to date, has the potential to be synergistic with cytotoxic chemotherapy agents. CLAG-M has shown compelling results in patients with relapsed or refractory disease and we believe that the combination with our ARC can improve response rates, transplant rates and overall survival for patients.”

AML is characterized by the swift expansion of white blood cells, and the enflamed cells impede the creation and development of classic blood cells. It initially presents in the bone marrow and quickly spreads to the blood. Abtimab-A, the leading drug candidate from the CD33 program, is an antibody radio-conjugate (ARC) that contains the CD33 targeting antibody lintuzumab and actinium-225, an alpha-emitting radioisotope.

CLAG-M is a salvage chemotherapy regimen made up of cladribine, cytarabine, filgrastim, and mitoxantrone. It is currently the standard of care in AML patients with relapse at several institutions across the U.S.

“We see the use of our ARC’s in combination with chemotherapy as an exciting development opportunity that has the potential to bring benefits to a significant number patients,” said Sandesh Seth, Actinium’s Chairman and CEO. “We believe that this will be the first of many combinations given the potency of our ARC approach together with its minimal extramedullary toxicities and its unique mechanism of action. Together these attributes make our ARC a versatile therapy that we believe can bring benefits to patients as a monotherapy, in combination and for myeloablation prior to a bone marrow transplant.”

Actimab-A is a second-generation therapy that was developed at Memorial Sloan Kettering Cancer Center. As of this writing, it has been studied in more than 100 patients across four clinical trials.

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