Phase 3 Trial of Iomab-B as an Induction and Conditioning Agent Prior to Bone Marrow or Stem Cell Transplant in Relapsed or Refractory AML Interview with:

Felix Garzon, MD, PhD Senior Vice President Head of Clinical Development Actinium Pharmaceuticals, Inc. New York, NY 10016

Felix Garzon

Felix Garzon, MD, PhD
Senior Vice President
Head of Clinical Development
Actinium Pharmaceuticals, Inc.
New York, NY 10016 What is the background for this study? What is goal of this Study?

Response: Iomab-B (“Iomab”) was developed at the Fred Hutchinson Cancer Research Center (“the Hutch”) in Seattle, Washington. The Hutch is a pioneer in the field of bone marrow transplantation (BMT) having 3 Nobel Prizes and doctors there performed some of the first transplants for leukemia patients. Iomab-B is intended to be an induction and conditioning agent prior to a BMT for patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are over the age of 55. BMT is the only potentially curative option for AML i.e. for this patient population that currently has a survival prognosis of 2-6 months which means that if Iomab-B is successful it would create a new market segment and offer patients a great clinical benefit and a hope for a cure. Actinium Pharmaceuticals licensed Iomab from the Hutch in 2012 and prior to us licensing Iomab, it had been studied in almost 300 patients in several phase 1 and phase 2 clinical trials in an array of blood cancers, both leukemias and lymphomas. Actinium is now the sponsor of a pivotal phase 3 trial for Iomab-B to study its use as an induction and conditioning agent prior to a bone marrow transplantation in patients with relapsed or refractory AML who are over the age of 55. This trial, which we have named the SIERRA (Study of Iomab-B in Elderly Relapsed or Refractory AML) trial, started at the end of June 2016 and we expect to enroll 150 patients by the end of 2017.

The primary endpoint of the SIERRA trial is durable complete remissions (dCR) of 6 months. The study arm will consist of Iomab-B administration followed by a  bone marrow transplantation, patients will be evaluated for dCR at 6 months after engraftment, which will be assessed at day 28 or day 56. The control arm of the study will be physician’s choice of chemotherapy and if the patient is able to achieve a complete remission (CR) they may receive a BMT or some other form of treatment with curative intent. The study is designed to evaluate if the study arm of Iomab-B and a BMT can double the dCR rate of the control arm, which is designed to replicate the current treatment regimen prior to a bone marrow transplantation . What differentiates Iomab-B from the chemotherapies that are used currently?

Response: Iomab-B has the potential to be more clinically effective than chemotherapy without the side effects of chemotherapy. Iomab-B is comprised of the anti-CD45 antibody, BC8, coupled with Iodine–131, a radioisotope. CD45 is a surface antigen expressed on proliferating leukemia cells, B cells and cancer stem cells. Through the emission of radiation energy, Iodine-131 is able to address the patient’s active disease (induction) and ablate their bone marrow (conditioning), thus preparing the patient for a BMT. Iomab-B is administered through 2 injections given on day 1 (dosimetric dose) and day 6 (therapeutic dose), which is then followed by a few days of reduced intensity conditioning (RIC) prior to the BMT. Chemotherapies currently utilized in preparing patients for a BMT are cytotoxic agents that are not targeted and they are given in cycles that can have durations of several days or weeks. Previous studies have shown that Iomab-B has fewer and less severe toxicities than chemotherapy, including a lower non-relapsed mortality rate (46% for chemotherapy vs. 10% for Iomab-B at day 100 and 20% overall). What types of blood disorders/leukemias/myeloproliferative diseases may benefit from a transplant? Does Iomab-B have any application for these conditions?

Response: Bone marrow transplantations are used in a wide array of blood cancers, disorders and myeloproliferative diseases. Examples of leukemias where a BMT may be utilized include AML, ALL (Acute lymphoblastic Leukemia), CML (Chronic Myelogenous Leukemia) and CLL (Chronic Lymphoblastic Leukemia).Other blood cancers, diseases and myeloproliferative diseases that may benefit from a BMT include Non-Hodgkin’s (N-HL) and Hodgkin’s Lymphoma (HL), Multiple Myeloma (MM) and Myelodysplastic Syndrome (MDS).

Iomab-B had been studied in almost 300 patients at the Hutch and in addition to AML it had been studied in MDS, ALL, N-HL and HL and MM. Iomab continues to be studied at the Hutch in these indications in physician sponsored trials and we believe it may be applicable in preparing these patients for a BMT also. What are the general guidelines for a transplant? How does one find a donor?

Response: Guidelines for a transplant vary widely based on the patient’s disease and condition. There are a number of ways one can find a donor.

First, one’s family members is often the first resource and represents the highest chance of finding a match or a person with the same human leukocyte antigen (HLA) tissue type. Beyond that, there are a number of organizations dedicated to connecting patients with matching donors, most notably, the National Marrow Donor Program (NMDP) and their Be The Match® program who manages the largest bone marrow registry in the world.

Finally, the hospital or medical center where a patient will receive their care and transplant may offer assistance in finding a donor. What kind of follow-up care is required after a transplant? What are the potential adverse effects?

Response: Patients will be followed closely after receiving a transplant, initially in an in-patient setting until the transplant has engrafted and the donor marrow begins to make new red blood cells, white blood cells and platelets. Once engrafted, a patient will likely to be able to move to an out-patient setting such as their home where they will continued to monitored for some time, often up to 1 year. In the almost 300 patients that were treated with Iomab-B at the Hutch, no unusual side effects were attributable to Iomab and most side effects are believed to be a result of the transplant itself. Potential complications from a transplant include anemia, graft failure, graft versus host disease, infection, organ damage and many other potential complications. Physicians and care givers follow transplant patients very closely with the goal of catching any potential complications early to manage them before they become severe.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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