Phase III AML Trial


Rafael Pharmaceuticals has Initiated a Phase 3 Trial (ARMADA 2000) of CPI-613® (devimistat) in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)

Rafael Pharmaceuticals, Inc. has initiated a Phase 3, multicenter, open-label, randomized, pivotal trial (ARMADA 2000) to evaluate the efficacy and safety of its lead compound, CPI-613® (devimistat), in combination with high dose cytarabine and mitoxantrone (“CHAM”) in older patients with relapsed or refractory acute myeloid leukemia (AML).

ARMADA 2000 will compare the efficacy and safety of high dose cytarabine and mitoxantrone (“HAM”, control arm) with the CHAM combination. Patients ≥ 60 years old with relapsed or refractory AML and an ECOG performance status of 0 to 2 are eligible for enrollment. The primary efficacy endpoint will be Complete Remission (CR). Secondary endpoints include the evaluation of Overall Survival (OS) and Complete Remission with Partial Hematologic Recovery (CRh) as well as safety.

A total of 500 patients will be evaluated in ARMADA 2000 at approximately 87 sites in 12 countries. The interim analysis of the study is expected to be completed as early as Q1 2020. More information on the trial is available at www.clinicaltrials.gov (NCT03504410).

An earlier Phase 1 dose escalation study (CCCWFU 22112) evaluated the safety, tolerabilityand efficacy of CHAM in patients with relapsed or refractory AML. In total, 67 patients were enrolled and 62 were evaluable for response. The overall response rate was 50% with median survival of 6.7 months. In a subsequent Phase 2 study (CCCWFU 22215) of CHAM, a total of 48 patients were enrolled and all were evaluable for response. The overall response rate
was 45% with median survival was 10.4 months. In the combined data of these two trials, elderly patients (≥ 60 years) with relapsed or refractory AML dosed with 2,000 mg/m 2  of CPI-613®, exhibited 52% CR+CRi with median survival of 12.4 months. In both studies, the treatment was well tolerated. Frequent adverse events included Anemia, Neutropenia, Thrombocytopenia, Leukocytopenia and Lymphopenia. Given these results, further evaluation of CPI-613® in the ARMADA 2000 Phase 3 trial is warranted.

Comments on this Study from Rafael Leadership:

Howard Jonas, Chairman of Rafael Pharmaceuticals: “It is not only our goal to prolong life but to keep working towards a cure for AML and other difficult to treat cancers. We have great hope both for the success of this trial and even better results in years to come with our follow-on compounds. We are optimistic that our cancer metabolism drugs may create a new paradigm in oncology treatment.”

Sanjeev Luther, President and Chief Executive Officer of Rafael Pharmaceuticals: “Our motto, ‘To Save A Life Is To Save A Universe,’ reflects our commitment to develop potential treatments for patients with significant unmet clinical needs. Initiation of our ARMADA 2000 trial is a significant milestone in that direction. We believe that CPI-613® has the potential to change the course of treatment in elderly patients with AML. Given that the clinical development of CPI-613® started at Wake Forest Baptist Health, we wanted this to be the site to enroll the first patient in this Phase 3 trial. We are grateful to all the individuals that have been involved with clinical development of CPI-613®. Given the importance of this trial we have partnered with a reputable contract research organization, IQVIA, for study execution.”

Jorge Eduardo Cortes, MD, Principal Investigator of this study: “This study explores a novel agent with a unique mechanism of action. The results from prior studies are very exciting and lead us to believe that CPI-613® may end up being a valuable addition to the AML armamentarium. Seeing the study started is inspiring.”

Timothy Pardee, MD, Ph.D., Chief Medical Officer of Rafael Pharmaceuticals: “I am very excited to see the initiation of this phase 3 trial for fit, older, AML patients who have failed targeted or hypomethylator salvage therapy. Currently, there are limited therapeutic options for this population.”

About CPI-613® (devimistat):

CPI-613® (devimistat) is a first-in-class drug developed based on Rafael Pharmaceuticals’ Altered Metabolism Directed (AMD) platform. CPI-613® targets altered regulation of metabolic processes specific to cancer cells. It is designed to be highly specific, to simultaneously attack multiple targets, to be minimally toxic and to have broad spectrum activity across a wide variety of cancers. CPI-613® is being or has been evaluated in 18 ongoing or completed trials as a single agent, as well as in combination with standard drug therapy for hematological malignancies and solid tumors. To date, over 300 patients have received one or more doses of CPI-613®. In pancreatic cancer, CPI-613® in combination with modified FOLFIRINOX exhibited an objective response rate of 61%, median overall survival of 19.9 months and median progression free survival of 9.9 months. In elderly patients with AML, CPI-613® in combination with high dose cytarabine and mitoxantrone exhibited 52% CR+CRi and 12.4 months median overall survival. In T-cell lymphoma, CPI-613® in combination with bendamustine exhibited a 75% overall response rate. CPI-613® has been granted orphan drug designation by the U.S. FDA for pancreatic cancer, AML, MDS, peripheral T-cell lymphoma and Burkitt’s lymphoma. The EMA has granted orphan drug designation to CPI-613® for pancreatic cancer and AML.

About Acute Myeloid Leukemia:

AML is a hematologic malignancy characterized by the accumulation of clonal myeloid progenitor cells (“blasts”) in the blood or bone marrow.1-3Malignant hematopoietic stem and myeloid progenitor cells proliferate uncontrollably and disrupt normal hematopoiesis, resulting in impairments in the ability of these myeloid progenitor cells to differentiate.4 Current prevalence of AML in the U.S. is approximately 40,000 and mortality rates range from 25% to 75% in patients under 60 years of age and >90% in elderly patients.2 Many patients who achieve a remission and complete consolidation therapy still have a guarded prognosis. This is driven by the fact that over 50% of patients will experience a relapse, and most relapsed patients will die from AML within a year. There is no consensus standard treatment for relapsed or refractory disease, but most fit patients are treated with a high dose cytarabine (HiDAC)-based regimen.5


References:

  1. Ferrara F, Schiffer CA. Acute myeloid leukaemia in adults. Lancet (London, England). 2013;381(9865):484-495.
  2. Gutierrez SE, Romero-Oliva FA. Epigenetic changes: a common theme in acute myelogenous leukemogenesis. Journal of hematology & oncology. 2013;6:57.
  3. Kubal T, Lancet JE. The thorny issue of relapsed acute myeloid leukemia. Current opinion in hematology. 2013;20(2):100-106.
  4. Pollyea DA, Kohrt HE, Medeiros BC. Acute myeloid leukaemia in the elderly: a review. British journal of haematology. 2011;152(5):524-542.

Disclosure:
-Tim Pardee MD; Ph.D. was the site principal investigator for early Phase I/II clinical trials at Wake Forest Baptist Medical Center.
-Bayard L. Powell, M.D., Section Chief, Hematology & Oncology, Associate Director for Clinical Research, Comprehensive Cancer Center, Professor, Hematology & Oncology, Wake Forest Baptist Medical Center serves as a member of Rafael Pharmaceuticals Medical Advisory Board.
-Boris Pasche MD; Ph.D. Director, Comprehensive Cancer Center and Chairman, Department of Cancer Biology, Wake Forest Baptist Medical Center, serves as a Board Member to Rafael Holdings, Inc. (NYSE American: RFL) which is an investor in Rafael Pharmaceuticals, Inc.

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Contact

Sanjeev Luther
President & CEO Rafael Pharmaceuticals, Inc.
sanjeev.luther@rafaelpharma.com

Timothy Pardee
Chief Medical Officer, Rafael Pharmaceuticals, Inc.
timothy.pardee@rafaelpharma.com