Iomab-B Leads to Durable Complete Remission in Phase 3 SIERRA Trial

Blood cancer cells under the microscope: © stock_acc - stock.adobe.com

Only the patients receiving an Iomab-B–led bone marrow transplant in the phase 3 SIERRA trial (NCT02665065) of patients aged 55 years and older with active relapsed/refractory acute myeloid leukemia (AML) achieved the study’s primary end point of durable complete remission (CR).¹ These patients demonstrated impressive survival rates, with 92% 1-year survival and 69% 2-year survival, alongside significantly higher event-free survival, according to findings presented at the 2024 European Hematology Association (EHA) Hybrid Congress.

Long-term data also showed that all patients receiving Iomab-B underwent a bone marrow transplant vs 18% on the control arm. In these arms, 75% and 6.3% of patients achieved a CR with durable CR rates of 22% for those in the Iomab-B arm vs 0% on the control arm.

At the meeting, 2 presentations highlighted findings from the SIERRA trial. Specifically, these studies focused on patients with active relapsed/refractory AML harboring a TP53 mutation and the long-term efficacy results in this older patient population. Durable CR is the primary end point of the SIERRA study.

SIERRA is a phase 3 trial which enrolled 153 patients aged 55 years and older with active relapsed/refractory acute AML. Investigators assessed the outcomes of patients receiving an Iomab-B–led bone marrow transplant and compared them with those of patients receiving physician's choice of care in the control arm.²

Patients were randomly assigned 1:1 to receive either Iomab-B then transplant or conventional care. Enrollment was open to patients 55 years or older with active disease and a bone marrow blast count of 5% or had the presence of circulating blasts. Patients were also eligible for enrollment if they had a Karnofsky Performance score of 70 or more, an 8/8 allele-level, or a related or unrelated matched donor; however, patients with previous transplant history were excluded.

Once enrolled, patients were administered either Iomab-B or conventional therapy, both prior to transplant. Patients in the control arm could receive chemotherapy with either cytarabine and daunorubicin or targeted therapy with a Bcl-2, FLT3, or IDH 1/2 inhibitor.

High-risk patients with 1 or more of the following were enrolled in the study: TP53 mutation, advanced age up to 77 years, complex cytogenetics, and prior therapy with venetoclax (Venclexta) and other targeted agents.¹

Additional findings from the studies showed that 24% (37/153) of patients enrolled in the SIERRA study had a TP53 mutation. The median overall survival (OS) for those with a TP53 mutation receiving an Iomab-B led allogeneic bone marrow transplant vs those who did not receive Iomab-B was 5.49 months vs 1.66 months in patients (HR, 0.23; P =.0002). Of the patients with TP53-negative disease, the median OS was 6.37 months, and for those with TP53-positive disease, the median OS was 5.72 months.

Further, the trial revealed Iomab-B to be well-tolerated with a favorable safety profile. Lower rates of sepsis and mucositis were also seen in patients receiving an Iomab-B–led bone marrow transplant.

REFERENCES:

1. Actinium highlights oral presentation at EHA 2024 Annual Congress featuring improved outcomes in TP53 positive patients receiving Iomab-B in the phase 3 SIERRA trial. News release. Actinium Pharmaceuticals, Inc. June 14, 2024. Accessed June 14, 2024. https://tinyurl.com/3m6ybnvf

2. Study of Iomab-B vs. conventional care in older subjects with active, relapsed or refractory acute myeloid leukemia (SIERRA). ClinicalTrials.gov. Updated July 19, 2023. Accessed June 14, 2024. https://clinicaltrials.gov/study/NCT02665065