100% Remission Rate Reported in Third Dose Cohort of Actimab-A CLAG-M Phase 1 Combination Trial in Patients with Relapsed or Refractory AML

Rhea-AI Summary

Actinium Pharmaceuticals (NYSE: ATNM) announced that 100% of evaluable patients in the third dose cohort of the Actimab-A CLAG-M Phase 1 trial achieved remission. Overall, 67% of patients across three cohorts reached either Complete Remission (CR) or Complete Remission with inadequate hematopoietic recovery (CRi). Notably, 70% of CR/CRi patients were MRD negative, showing no detectable disease. With an acceptable safety profile, a fourth dose cohort is now being explored. Results will be presented at the ASH annual meeting on December 5, 2020.

Positive

• 100% remission rate in the third dose cohort.
• 67% overall CR/CRi rate across three cohorts.
• 70% of CR/CRi patients achieved MRD negativity.
• Encouraged data indicating potential combination therapy efficacy.

Negative

• None.

NEW YORK, Nov. 4, 2020 /PRNewswire/ -- Actinium Pharmaceuticals, Inc.  (NYSE AMERICAN: 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 Presentation Title:	A Phase I Study of Lintuzumab Ac225 in Combination with CLAG-M Chemotherapy in Relapsed/Refractory AML
Publication Number:	165
Session Name:	616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Advances in immunotherapeutics for management of AML
Session Date:	Saturday, December 5, 2020
Presentation Time:	12:00 PM PT / 3:00 PM ET

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

About Actinium's CD33 Program

Actinium's CD33 program is evaluating the clinical utility of Actiamb-A, an ARC comprised of the anti-CD33 mAb lintuzumab linked to the potent alpha-emitting radioisotope Actinium-225 or Ac-225. CD33 is expressed in the majority of patients with AML and myelodysplastic syndrome, or MDS, as well as patients with multiple myeloma. The CD33 development program is driven by data from over one hundred treated patients, including a Phase 1/2 trial where Actimab-A produced a remission rate as high as 69% as a single agent.  This clinical data is shaping a two-pronged approach for the CD33 program, where at low doses the Company is exploring its use for therapeutic purposes in combination with other modalities and at high doses for use for targeted conditioning prior to bone marrow transplant. Actinium currently has multiple clinical trials ongoing including the Phase 1 Actimab-A CLAG-M and Phase 1/2 Actimab-A venetoclax combination trials and is exploring additional CD33 ARC combinations with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy.

About Actinium Pharmaceuticals, Inc. (NYSE: ATNM)

Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing ARCs or Antibody Radiation-Conjugates, which combine the targeting ability of antibodies with the cell killing ability of radiation.  Actinium's lead application for our ARCs is targeted conditioning, which is intended to selectively deplete a patient's disease or cancer cells and certain immune cells prior to a BMT or Bone Marrow Transplant, Gene Therapy or Adoptive Cell Therapy (ACT) such as CAR-T to enable engraftment of these transplanted cells with minimal toxicities.  With our ARC approach, we seek to improve patient outcomes and access to these potentially curative treatments by eliminating or reducing the non-targeted chemotherapy that is used for conditioning in standard practice currently.  Our lead product candidate, I-131 apamistamab (Iomab-B) is being studied in the ongoing pivotal Phase 3 Study of Iomab-B in Elderly Relapsed or Refractory Acute Myeloid Leukemia (SIERRA) trial for BMT conditioning.  The SIERRA trial is over seventy-five percent enrolled and positive single-agent, feasibility and safety data has been highlighted at ASH, TCT, ASCO and SOHO annual meetings.  More information on this Phase 3 clinical trial can be found at sierratrial.com. I-131 apamistamab will also be studied as a targeted conditioning agent in a Phase 1 study with a CD19 CAR T-cell Therapy and Phase 1/2 anti-HIV stem cell gene therapy with UC Davis.  In addition, we are developing a multi-disease, multi-target pipeline of clinical-stage ARCs targeting the antigens CD45 and CD33 for targeted conditioning and as a therapeutic either in combination with other therapeutic modalities or as a single agent for patients with a broad range of hematologic malignancies including acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma.  Ongoing combination trials include our CD33 alpha ARC, Actimab-A, in combination with the salvage chemotherapy CLAG-M and the Bcl-2 targeted therapy venetoclax.  Underpinning our clinical programs is our proprietary AWE (Antibody Warhead Enabling) technology platform.  This is where our intellectual property portfolio of over 100 patents, know-how, collective research and expertise in the field are being leveraged to construct and study novel ARCs and ARC combinations to bolster our pipeline for strategic purposes.  Our AWE technology platform is currently being utilized in a collaborative research partnership with Astellas Pharma, Inc. Website: https://www.actiniumpharma.com/

Forward-Looking Statements for Actinium Pharmaceuticals, Inc. 

This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.

Contacts:

Investors:
Clayton Robertson
Actinium Pharmaceuticals, Inc.
crobertson@actiniumpharma.com

Hans Vitzthum
LifeSci Advisors, LLC
Hans@LifeSciAdvisors.com 
(617) 430-7578

View original content to download multimedia:http://www.prnewswire.com/news-releases/100-remission-rate-reported-in-third-dose-cohort-of-actimab-a-clag-m-phase-1-combination-trial-in-patients-with-relapsed-or-refractory-aml-301166491.html

SOURCE Actinium Pharmaceuticals, Inc.

FAQ

What were the results of the Actimab-A CLAG-M Phase 1 trial for ATNM?

The trial reported a 100% remission rate in the third dose cohort, with an overall 67% CR/CRi rate across all cohorts.

When will the results of the Actimab-A trial be presented?

Results will be presented at the American Society of Hematology (ASH) annual meeting from December 5-8, 2020.

What does MRD negativity mean in the context of the trial results for Actinium Pharmaceuticals?

MRD negativity indicates that no detectable disease was found in 70% of the patients who achieved CR or CRi.

What is the significance of the new dose cohort being added in the trial?

A fourth dose cohort is being added as the previous cohorts showed promising results and an acceptable safety profile.

What is Actinium Pharmaceuticals focusing on in the ongoing clinical trials?

Actinium is exploring the efficacy of Actimab-A in combination with other therapies for treating relapsed or refractory acute myeloid leukemia.