information: DSMB assessment
Announcement: DSMB assessment
Company: Actinium Pharmaceuticals (USA - NJ)
Product: Iomab-B (131I apamistamab)
- monoclonal antibody/radioimmunotherapy. Iomab-B (BC8-I-131 construct) is a radioimmunotherapy comprised of the monoclonal antibody BC8 coupled with the radioisotope Iodine-131 that is designed to deliver targeted payloads to cells that express CD45, a pan-leukemic antigen expressed on white blood cells and stem cells. Once attached to its target cells, the radioisotope, I-131, emits energy that travels a relatively long distance, destroying a patient's cancer cells and bone marrow.
Disease: acute myeloid leukemia (AML)
area: Cancer - Oncology
Country: Canada, USA
- The SIERRA (Study of Iomab-B in Elderly Relapsed or Refractory AML) trial is a a 150 patient, multi-center, randomized, controlled pivotal Phase 3 study of Iomab-B in patients with relapsed or refractory acute myeloid leukemia (AML) who are over the age of 55.
- The primary endpoint of the trial is durable Complete Remission (dCR) at 6 months.The primary endpoint in the pivotal Phase 3 trial is durable complete remission, defined as a complete remission lasting at least 6 months and the secondary endpoint will be overall survival at one year.
- The primary objective of this study is to demonstrate the efficacy of Iomab-B, in conjunction with a Reduced Intensity Conditioning (RIC) regimen and protocol-specified allogeneic hematopoietic stem cell transplant (HCT), versus Conventional Care.
- Actinium Pharmaceuticals has established an agreement with the FDA that the path to a Biologics License Application (BLA) submission could include the SIERRA trial, if it is successful. (NCT02665065)
- • On December 27, 2017, Actinium Pharmaceuticals announced that the Independent Data Monitoring Committee (DMC) for the Pivotal Phase 3 SIERRA Trial (Study of Iomab-B for Elderly Relapsed or Refractory AML) of Iomab-B (131I apamistamab) completed its review of the data available from the trial at time of analysis. The DMC recommended that the trial continue to enroll patients as planned.
- The DMC has reviewed initial safety data from the first 20 patients enrolled in the trial at its regularly scheduled late November meeting. Actinium expects that the company will be able to complete patient enrollment by the end of 2018. The fifteenth SIERRA clinical trial site had been activated at the end of October 2017. The SIERRA clinical trial sites are some of the leading and highest volume BMT centers in the US including the MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, the Mayo Clinical, the Fred Hutchinson Cancer Research Center and many others. Together, these active sites account for approximately one third of bone marrow transplant related volume. Actinium previously commented that once a site has treated its initial patient with Iomab-B, recruitment and enrollment accelerates at that site. In addition, to continuing to devote attention to activated sites in order to meet enrollment objectives, Actinium intends to continue to also focus on activating additional clinical trial sites and educating site staff in order to build on the strong foundation for patient enrollment.
- In 2018, Actinium expects to open the SIERRA trial at 5-7 additional clinical trial sites including sites in Canada where the company received clearance to initiate the trial from Health Canada in 2017.
- In addition, Actinium announced that it will amend the protocol of the SIERRA trial to expand the salvage chemotherapy regimens available in the control arm of the study, following the feedback from investigators at trial sites and the advice of its Scientific Advisory Board that was convened during the recent ASH meeting. The company expects that being responsive to investigator suggestions and amending the protocol removes a hindrance to enrollment at some of the major sites as it provides investigators with the ability to better enroll patients.
- Actinium also reported that it has successfully supplied dosimetric and therapeutic doses as needed to all patients in the study arm and to all of the patients that have crossed over to the Iomab-B arm from the control arm thus far. Patients that cross over from the control arm are counted as failures for the primary endpoint of durable Complete Remission of at least 6 months. The company has stated that in 2017 it manufactured additional antibody at commercial scale, and has sufficient quantities to account for the current trial and the planned potential label expansion initiatives in 2018.
The SIERRA trial is expected to complete patient enrollment by the end of 2018 which is in line with prior guidance from the company. The trial will have safety analyses by an independent Data Monitoring Committee when 25%, 50% and 75% patient enrollment has been reached. Also, two ad-hoc efficacy analyses may be requested by Actinium after 70 and/or 110 patients have engrafted and given enough time to achieve the primary endpoint of durable complete remission at six months post treatment.
- • On May 10, 2017, Actinium Pharmaceuticals announced that the company received clearance from Health Canada to initiate the pivotal Phase 3 SIERRA Trial of Iomab-B at Canadian based clinical trial sites. The SIERRA trial is a 150-patient, randomized, multicenter pivotal study evaluating Iomab-B followed by an HSCT in patients with relapsed or refractory acute myeloid leukemia who are age 55 and above compared to physician’s choice of chemotherapy that patient’s in the control arm will receive. According to the Canadian Blood and Marrow Transplant Group (CBMTG), there are approximately 15 centers in Canada that perform blood and marrow transplants who participate in the CBMTG’s registry. In CBMTG’s 2015/2016 annual report, it reported that there were 7,693 allogeneic transplants performed in Canada including 2,417 for patients with AML.
- • On March 21, 2017, Actinium Pharmaceuticals announced that the company has received positive Scientific Advice from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) related to the EU approval pathway for Iomab-B. In its correspondence to Actinium, the EMA commented that the trial design, primary endpoint and planned statistical analysis of the U.S. pivotal Phase 3 SIERRA trial are acceptable and can serve as the basis for submission of a Marketing Authorization Application. In addition, the EMA commented that it does not anticipate the need for further standalone preclinical toxicology or safety studies.
- • On June 29, 2016, Actinium Pharmaceuticals announced that the pivotal Phase 3 clinical trial for Iomab-B has been initiated. Iomab-B, the Company's lead asset, upon approval, is intended to be an induction and conditioning agent used to prepare patients with relapsed or refractory acute myeloid leukemia who are over the age of 55 for a hematopoietic stem cell transplant. The SIERRA trial will include independent Data Monitoring Committee (DMC) reports, which will occur at 25, 50, 75 and 100 percent patient enrollment with the potential for two additional ad-hoc DMC reports. Approximately 150 medical centers provide AML bone marrow transplants, with the top 30 centers performing over 50 percent of the AML BMT procedures. Actinium expects many of the highest volume BMT centers to participate in the SIERRA trial given that the results of previous studies in almost 300 patients have demonstrated the potential of Iomab-B to create a new treatment paradigm for bone marrow transplants by: expanding the pool to ineligible patients who do not have any viable treatment options currently; enabling a shorter and safer preparatory interval for HSCT; reducing post-transplant complications; and showing a clear survival benefit including curative potential.