Benzinga | Nov 4, 2020 12:24PM EST

Actinium Pharma Reports 100% Of Evaluable Patients In Third, Planned Final Dose Cohort Of Actimab-A CLAG-M Phase 1 Trial Being Conducted At Medical College Of Wisconsin Achieved Remission

Actinium Pharmaceuticals, Inc. (NYSE:ATNM) ("Actinium") today announced that 100% of evaluable patients in the third and planned final dose cohort of the Actimab-A CLAG-M Phase 1 trial being conducted at the Medical College of Wisconsin (MCW) achieved remission. Across all three cohorts, 67% or 10/15 patients treated with 0.25, 0.50 and 0.75 uCi/kg of Actimab-A and the standard regimen of CLAG-M achieved a Complete Remission (CR) or Complete Remission with inadequate hematopoietic recovery (CRi). Further, 83% of patients (10/12) who received 3 or fewer prior lines of treatment achieved CR or CRi. Notably, 70% of CR/CRi patients were MRD negative indicating a deep remission with no detectable disease. These results which include subtherapeutic doses of Actimab-A in the first two dose cohorts and represent a marked improvement over CLAG-M treatment alone (ORR: 55%, MRD negativity: 39%) implying potential mechanistic synergy. This novel Phase 1 combination trial is for patients with relapsed or refractory acute myeloid leukemia (R/R AML) age 18 and above deemed medically fit for cytotoxic chemotherapy. This data has been accepted for oral presentation at the 2020 American Society of Hematology (ASH) annual meeting that is being held virtually December 5-8, 2020.



Dr. Mark Berger, Actinium's Chief Medical Officer, commented, "We are thrilled with the high rates of remission, MRD negativity and transplant in this trial, which highlights the potential this combination may have for patients with R/R AML. Actimab-A targets CD33, which is expressed in virtually all patients with AML, and delivers potent radiation via the alpha-emitting radioisotope Actinium-225. Actimab-A has produced single-agent response rates as high as 69% in a Phase 2 trial, demonstrating its potential in radiation sensitive blood cancers like AML. While the synergies of radiation with chemotherapy and other modalities is well known, we are highly encouraged that Actimab-A at low doses with CLAG-M produced higher rates of remission and MRD negativity than either agent alone, supporting the synergy of this combination and potential of other Actimab-A combinations. It's still the case that there is no standard of care for R/R AML despite it being a large segment of the AML patient population. Our efforts with our CD33 program are intended to show that Actimab-A, when used together with other synergistic therapeutic modalities, can serve as the backbone of combinations that we hope will be new standards of care for both fit and unfit patients with R/R AML. With supporting data also being reported from our Actimab-A venetoclax combination trial we have great enthusiasm of the potential of additional Actimab-A combination with other therapeutic agents, that can treat patients with significant unmet need."

Patients enrolled on this study to date had intermediate (5/15, 33%) or adverse (10/15, 67%) cytogenetics. Patients received a median of 2 lines of prior therapies (range 1-5) with 47% of patients (7/15) previously receiving venetoclax with a hypomethylating agent and 53% of patients (8/15) having undergone an allogeneic BMT and then relapsed prior to Actimab-A CLAG-M. In the third dose cohort of 0.75 uCi/kg, 100% of evaluable patients (3/3) achieved complete remission [1 CR, 2 Complete Remission with inadequate platelet recovery (CRp)] with 2 patients being MRD negative and the other patient having only 0.2% AML cells detected. MRD negativity is defined as ?0.1% AML cells. Investigators at MCW determined that the combination had a clinically acceptable safety profile, including at the planned final dose cohort of 0.75 uCi/kg, and have therefore amended this protocol to add a fourth dose cohort of 1.0 uCi/kg, which is currently screening and enrolling patients.

Dr. Berger added, "We look forward to continuing our work with the investigators at MCW in the expanded dose cohort. Given the complexity of treating patients with R/R AML we feel it is appropriate to continue to explore this novel combination to ensure we identify the ideal dose level. It is exciting to see the profile of this combination emerge not only for therapeutic purposes but also for its potential as a bridge to transplant as noted by the investigators at MCW."

Presentation Details

Oral A Phase I Study of Lintuzumab Ac225 in Combination with CLAG-MPresentation Chemotherapy in Relapsed/Refractory AMLTitle:

Publication 165Number:

616. Acute Myeloid Leukemia: Novel Therapy, excludingSession Name: Transplantation: Advances in immunotherapeutics for management of AML

Session Date: Saturday, December 5, 2020

Presentation 12:00 PM PT / 3:00 PM ETTime:

The complete abstracts are available on the ASH website (click here).