On February 25, 2019 Actinium Pharmaceuticals, Inc. (NYSE American: ATNM), reported that new data from the ongoing pivotal Phase 3 SIERRA trial for Iomab-B was reported in a late breaking oral presentation at the 2019 Transplantation & Cellular Therapy Meetings of ASBMT and CIBMTR (TCT Meetings) that was held on February 20th – 24th (Press release, Actinium Pharmaceuticals, FEB 25, 2019, View Source [SID1234533624]). Dr. Sergio Giralt, Chief, Adult Bone Marrow Transplant Service at Memorial Sloan Kettering Cancer Center presented the late breaking oral presentation. It was reported that all patients who received Iomab-B, received a BMT or Bone Marrow Transplant with 100% (28/28) of patients achieving engraftment and Donor Chimerism. The new data indicated that 92% (26/28) of these patients achieved Full Donor Chimerism prior to day 100, which is defined as at least 95% of donor cells being engrafted in the recipient. Full Donor Chimerism prior to day 100 is a clinically significant outcome that indicates acceptance of donor cells and transplant success.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited that data from the SIERRA trial continue to demonstrate strong engraftment, particularly in this patient population who have limited access to BMT, which is the only curative treatment option, with current chemotherapy based conditioning approaches", said Dr. Mark Berger, Actinium’s Chief Medical Officer. "Full Donor Chimerism is an important metric in this setting that indicates patients receiving Iomab-B are having successful transplants, which is significant for the SIERRA trial. I am delighted that we were able to report these new data on strong donor chimerism to the transplant community at the TCT Meetings after reporting at ASH (Free ASH Whitepaper) in December that all patients receiving Iomab-B received a BMT and achieved engraftment. We are motivated by the positive reception that the engraftment, safety and feasibility data have received from trial investigators and referring physicians. These data from the SIERRA trial will serve us well as we work to complete enrollment of the SIERRA trial and bring this important therapy to patients with significant unmet needs."

The SIERRA trial (Study of Iomab-B in Elderly Relapsed or Refractory AML) is a 150-patient pivotal Phase 3 multi-center randomized trial that will compare outcomes of patients who receive Iomab-B and a BMT to those patients receiving physician’s choice of salvage chemotherapy, defined as conventional care, as no standard of care exists for this patient population. The primary endpoint of the SIERRA trial is dCR or durable Complete Remission of 6 months. The SIERRA trial is currently enrolling patients at 18 sites in the U.S and Canada including many of the leading BMT sites based on volume. Patients with active, relapsed or refractory AML have dismal prognoses and are typically not offered potentially curative transplant as an option, largely because salvage treatments have a limited ability to produce a complete remission, which is necessary prior to conventional BMT if conventional BMT is to be successful. However, with Iomab-B targeted conditioning, a complete remission prior to starting the Iomab-B conditioning is not necessary for a successful transplant. Iomab-B is an ARC or Antibody Radiation-Conjugate that targets CD45, an antigen expressed on leukemia, lymphoma and immune cells, and delivers Iodine-131 that kills targeted cells via linear energy transfer. Safety and feasibility data from the first 38 patients (25% of planned enrollment) in the SIERRA trial including donor chimerism data that were presented in a late breaking oral session at TCT can accessed here. Additional safety and feasibility analyses will occur when 50% and 75% of patients have been enrolled. The SIERRA trial also permits ad hoc interim analyses that may be requested at Actinium’s discretion to assess safety and efficacy when 70 and 110 patients have reached the primary endpoint of 6-month dCR. However, these interim analyses will not expend meaningful alpha and repowering of the study is not required as trial size cannot be increased after an Ad-hoc interim analysis.

Key highlights from the SIERRA Trial presented at ASH (Free ASH Whitepaper) and the TCT Meetings include:

All patients receiving a therapeutic dose of Iomab-B engrafted despite active disease with high blast count (median 30%, or median 45% for crossover patients)
15 of 19 (79%) patients in the control arm failed to achieve a complete response
67% (10/15) of patients eligible for crossover successfully transplanted after Iomab-B treatment
Patients receiving Iomab-B received a BMT more quickly post-randomization (28 days) than patients receiving conventional care (67 days)
In the conventional care arm, there was no difference in time to BMT for patients that crossed over to Iomab-B (66 days) compared to those achieving complete remission with conventional care (67 days)
No Grade 3 or 4 Iomab-B infusion related reactions with all Iomab-B infusions completed
No 100-Day non-relapse mortality in patients randomized to Iomab-B arm
All patients receiving Iomab-B and a BMT (28/28) achieved Donor Chimerism prior to day 100
94% of patients initially randomized to receive Iomab-B and a BMT (17/18) achieved Full Donor Chimerism > 95% prior to day 100 with 1 patient achieving 65% donor chimerism
90% of patients who crossed-over to receive Iomab-B and a BMT (9/10), after salvage chemotherapy in the control arm failed to produce a CR or Complete Response, also achieved Full Donor Chimerism > 95% prior to day 100 with 1 patient achieving 86% donor chimerism
Sandesh Seth, Actinium’s Chairman and CEO said, "Iomab-B has been studied extensively across multiple clinical trials and disease indications where it has consistently demonstrated the ability to condition patients for BMT in a well-tolerated manner with high engraftment rates and improved clinical outcomes including a survival benefit. As the lead candidate in our pipeline, it is heartening to see interim safety and feasibility data consistent with prior clinical evidence as the trend of strong engraftment with Iomab-B continues in the pivotal multi-center SIERRA trial. In addition, our other posters at TCT supporting the value proposition of Iomab-B from a healthcare economics perspective are also illuminative of the potential opportunity available. We are also excited to note the strong data from the Iomab-ACT program for targeted lymphodepletion prior to CART and other adoptive cell therapies supportive of clinical advancement that was presented at this TCT Meeting. We look forward to providing additional updates as we continue to build and advance our industry leading, multi-asset, multi-indication targeted conditioning portfolio."