On July 23, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported that the 75th patient has been treated in the pivotal Phase 3 SIERRA trial of Iomab-B, thus achieving 50 percent patient enrollment for the trial (Press release, Actinium Pharmaceuticals, JUL 23, 2019, View Source [SID1234537663]).
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The SIERRA trial or Study of Iomab-B in Elderly Relapse Refractory Acute Myeloid Leukemia is the only randomized Phase 3 trial that offers BMT or bone marrow transplant as an option for older patients with active, relapsed or refractory AML or acute myeloid leukemia. BMT is the only potentially curative treatment option for patients with relapsed or refractory AML and there is no standard of care for this indication. Iomab-B is an ARC or Antibody Radiation-Conjugate comprised of the anti-CD45 antibody apamistamab and the radioisotope I-131 or iodine-131. The 19 active SIERRA trial sites in the U.S. and Canada represent many of the leading bone marrow transplant centers by volume.
Dr. Mark Berger, Actinium’s Chief Medical Officer, said, "We are delighted to reach this key milestone in the SIERRA trial. The positive data thus far has lately translated to great enthusiasm from the trial sites for the study, and we believe this milestone will provide additional impetus. SIERRA is a first of its kind trial and to reach this point, our team has worked diligently to connect all stakeholders within the trial sites, obtain referrals of these patients who would not normally be considered for transplant, satisfy all regulations and establish a supply chain to service many of the leading transplant centers in the U.S. and Canada. In addition, we have made several protocol modifications that resulted in a stronger and more efficient trial. With 19 active clinical trial sites, positive preliminary feasibility and safety data and strong investigator enthusiasm, I believe the hardest part of the trial is now behind us. Our SIERRA team, which includes experts in AML, BMT, patient care, drug administration, radiation sciences and trial operations, is stronger and more committed than ever to the execution of SIERRA. Together we bring a multi-disciplinary approach to every patient screened for the SIERRA trial and will work tirelessly to complete a successful trial that can bring this important therapy to patients underserved by current treatment options."
Preliminary feasibility and safety data from the first twenty-five percent of patients enrolled in the SIERRA trial were presented at several key medical conferences, including at an oral presentation at ASH (Free ASH Whitepaper) 2018, in a late breaking oral presentation at TCT 2019, and in a poster at ASCO (Free ASCO Whitepaper) 2019. Key highlights from this data include:
ASH 2018 – Oral Presentation of Preliminary Feasibility and Safety Data
Conclusion: Encouraging results with potential to broaden transplant eligibility and improve outcomes
100% (18/18) of patients randomized and receiving the Iomab-B therapeutic dose received a BMT and achieved rapid engraftment
79% (15/19) of patients randomized to conventional care did not achieve CR or Complete Remission and could not receive a BMT
67% (10/15) of patients who failed to achieve get a BMT with conventional care still met the eligibility criteria and were able to cross over and receive Iomab-B
100% (10/10) of patients that crossed over and received the Iomab-b achieved engraftment without delay
Rapid engraftment achieved despite high blast counts
30% median blast count for Iomab-B patients (range:4-74%)
45% median blast count for crossover patients at time of crossover (range:10-70%)
Patients receiving Iomab-B received a BMT in a median time of 28 days compared to a median of 67 days for patients receiving conventional care who achieved CR and received a conventional BMT
0% (0/18) 100-day non-relapse mortality for Iomab-B patients compared to 25% (1/4) 100-day non-relapse mortality for conventional care patients achieving CR and receiving conventional transplant
TCT 2019 – Late Breaking Oral Presentation of Additional Feasibility and Safety Data
New Findings: Conditioning with Iomab-B results in Full Donor Chimerism, indicating successful bone marrow transplant
94% (17/18) of patients randomized to Iomab-B achieved Full Donor Chimerism > 95% within 100 days post-BMT with 1 patient achieving 65% donor chimerism
90% (9/10) of patients who crossed-over to receive Iomab-B achieved Full Donor Chimerism > 95% within 100 days post-BMT with 1 patient achieving 86% donor chimerism
ASCO 2019 – Poster Presentation of Iomab-B Single Agent Activity
Conclusion: Iomab-B as a single-agent rapidly clears circulating leukemic blasts leading to targeted myeloablation and successful engraftment after BMT, which benefits patients who had prolonged neutropenia due to active and refractory disease prior to transplant
Iomab-B as a single agent produced a 98% reduction in peripheral blasts by day 3 and a 100% reduction in peripheral blasts by day 8 leading to a significantly lower circulating leukemia tumor burden prior to BMT
Time to clearance of circulating tumor blasts shown to be an independent prognostic marker for Relapse-Free Survival in patients receiving chemotherapy that superseded all other known risk factors including karyotype and number of cycles of induction therapy needed to achieve CR1.
Dr. Vijay Reddy, VP, Clinical Development and Head of Transplant at Actinium, added, "I am thrilled with the data we have seen from the SIERRA trial thus far. This strong and supportive data being prominently featured at three major medical conferences has resulted in robust appreciation and interest for the SIERRA trial from sites and investigators. This has facilitated extensive site visits and interactions where we have highlighted the robust body of evidence supporting Iomab-B and SIERRA to transplant physicians, referring hematologists and caregivers at current and prospective sites, which have been well received. We will continue an extensive outreach effort to highlight the universal engraftment seen in all patients receiving Iomab-B despite high leukemia burden, the high BMT and engraftment rates for patients who fail the control arm and crossover to receive Iomab-B, and Iomab-B’s strong single agent activity. Our team is excited to continue our efforts to drive further interest for patient enrollment, and we are optimistic for the remainder of the SIERRA trial based on the data we have observed thus far, which is trending in line with results shown by Iomab-B in several prior Phase 2 trials."
Sandesh Seth, Actinium’s Chairman and CEO, said, "I am proud of our team for reaching this key milestone in the SIERRA trial as it represents a major inflection point for Actinium. Iomab-B is our lead asset for targeted conditioning prior to a BMT. Targeted conditioning is an area of opportunity and unmet medical need for which we have assembled a multi-target pipeline of assets for several attractive indications. We believe we can create significant value by focusing on targeted conditioning indications where, due to safety and efficacy issues related to existing regimens, patients either cannot access, or receive sub-optimal results from, potentially lifesaving therapies such as BMT, CAR-T and other adoptive cell therapies. Our vision is to create the leading franchise producing multiple therapies for BMT, CART-T and cell therapy-related targeted conditioning and to deliver them via a world-class supply chain and commercial organization to the concentrated number of leading medical centers that treat a majority of patients receiving these therapies. We are confident that Iomab-B and the SIERRA trial can become the linchpin to make this vision a reality, and we are fully committed to achieving near-term success with the SIERRA trial and long-term value with our multi-asset, targeted conditioning pipeline."
Sources:
1) Elliott et al. Early peripheral blood blast clearance during induction chemotherapy for acute myeloid leukemia predicts superior relapse-free survival. Blood. 2007 Dec 15; 110(13):4172-4. Epub 2007 Oct 1.