On November 6, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported that interim results from a Phase 1 trial studying Actimab-A in combination with CLAG-M have been accepted for presentation at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting that is being held December 7-10, 2019 in Orlando, FL (Press release, Actinium Pharmaceuticals, NOV 6, 2019, View Source [SID1234550432]). This is the first study to combine radioimmunotherapy and intensive chemotherapy in patients with relapsed or refractory AML. Actimab-A is an antibody radiation-conjugate (ARC) comprised of the CD33 targeting antibody lintuzumab labeled with the alpha-emitting radioisotope actinium-225 (Ac-225).

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!

The ASH (Free ASH Whitepaper) abstract reports on 9 adult patients with relapsed or refractory AML enrolled on the investigator-initiated trial at the Medical College of Wisconsin (MCW). Patients were a median age of 59 and had received a median of 2 (range 1-4) anti-leukemic treatments, including 4 patients who relapsed after receiving a bone marrow transplant (BMT). Patients received the salvage chemotherapy regimen cladribine, cytarabine, G-CSF, and mitoxantrone (CLAG-M) and a single dose of Actimab-A on either day 6, day 7, or day 8. Cohort 1 enrolled 3 patients who received 0.25 uCi/kg of Actimab-A and Cohort 2 enrolled 6 patients who received 0.50 uCi/kg of Actimab-A.

Details and highlights from Actinium’s accepted poster include:

Title: Lintuzumab Ac-225 in Combination with CLAG-M Chemotherapy in Relapsed/Refractory AML: Interim Results of a Phase I Study

Key Highlights:

83% of patients (5/6) receiving 0.50 uCi/kg of Actimab-A and CLAG-M in the second dosing cohort achieved a Complete Remission (CR), Complete Response with incomplete platelet recovery (CRp) or Complete Response with incomplete hematologic recovery (CRi)
83% remission rate with 0.50 uCi/kg Actimab-A CLAG-M combination significantly higher than the MCW institutional 54% remission rate with CLAG-M alone1
83% remission rate at 0.50 uCi/kg included 50% (3/6) with a CR
33% of patients (3/9) enrolled in the trial subsequently received a bone marrow transplant
Combining lower doses of Actimab-A with CLAG-M appears to have a clinically acceptable safety profile
All patients completed the planned cycle of Actimab-A and CLAG-M
No mortalities were observed on study
Poster Details:
Publication Number: 2605
Session Name: 613. Acute Myeloid Leukemia: Clinical Studies: Poster II
Date: Sunday, December 8, 2019
Presentation Time: 6:00 PM – 8:00 PM
Location: Orange County Convention Center, Hall B

Dr. Mark Berger, Actinium’s Chief Medical Officer, said, "It is quite encouraging to see a high overall response rate with the addition of Actimab-A compared to patients treated with CLAG-M alone. These preliminary results exceed our expectations and compare quite favorably to results seen with recently approved AML therapies, especially in these difficult to treat relapsed or refractory patients. We look forward to seeing additional results from this trial and are excited by the potential to advance the Actimab-A CLAG-M combination to a Phase 2 or potentially pivotal trial. In addition, the ability to combine Actimab-A with a powerful salvage regimen like CLAG-M with a manageable adverse event profile suggests that combinations with other agents, such as venetoclax, may also be tolerable and will lead to improved efficacy."

Sandesh Seth, Actinium’s Chairman and CEO, said, "These results strengthen our conviction in the potentiating and synergistic properties of targeted radiation with other therapeutic modalities. We see opportunities to combine our ARCs with chemotherapy as highlighted in this study, with targeted agents as we have done with our Actimab-A venetoclax combination trial and potentially with immunotherapy. Additionally, the rate of patients going to transplant in this study, despite the low dose levels of Actimab-A administered, gives us great excitement for our Actimab-MDS program that will study significantly higher doses of Actimab-A as a targeted conditioning regimen prior to a bone marrow transplant in patients with high-risk MDS. It is exciting to see our CD33 program development strategy with low-dose combinations and high-dose targeted conditioning generate positive responses and we look forward to additional data from our ongoing and planned clinical trials."

About Actimab-A

Actimab-A (actinium-225 lintuzumab) is an antibody radiation-conjugate that has been studied in over 100 patients in 4 clinical trials at several dose levels. A Phase 2 trial studying Actimab-A as a single agent produced a 69% overall response rate in older unfit patients with newly diagnosed AML. The findings from this study are supporting a development strategy that will study Actimab-A at high doses for targeted conditioning prior to bone marrow transplant in the planned pivotal Actimab-MDS program, and at lower doses in combination with other therapeutic modalities like the combination trial with the Bcl-2 inhibitor venetoclax and the combination trial with the chemotherapy regimen CLAG-M.