Actimab-A (lintuzumab-Ac225) / Actinium - LARVOL DELTA

Testing the Combination of Targeted Radiotherapy With Anti-Cancer Drugs, Venetoclax and ASTX-727, to Improve Outcomes for Adults With Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=53 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

Trial suspension • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Updated Results from Phase 1 Study of Targeted Radiotherapy with Lintuzumab-Ac225 in Combination with Venetoclax in Relapsed/Refractory AML (ASH 2023) - "The combination of lintuzumab-Ac225 and venetoclax had a manageable safety profile and no early mortality at day 30. The MTD was not reached and no significant toxicities have been reported during the follow-up period. Modified dosing schedule in Cohort 4 of the combination demonstrated improved anti-leukemic effects."

Combination therapy • IO biomarker • P1 data • Acute Myelogenous Leukemia • Cardiovascular • Heart Failure • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Thrombocytopenia • BCL2L1 • CD33

Outcome of Patients with TP53 Mutated Relapsed/Refractory AML with Lintuzumab-Ac225 in Combination with CLAG-M Following Venetoclax Plus Hypomethylating Agent Therapy (ASH 2024) - "Among these patients who were fit for intensive therapy, our data indicated that CLAG-M followed by Lintuzumab-Ac225 had a tolerable safety profile and yielded high responses with high MRD negativity translating to improved overall survival including in patients with TP53 mutated AML. Given these promising results in a historically challenging patient population, these results support a larger clinical study investigating CLAG-M followed by Lintuzumab-Ac225."

Clinical • Combination therapy • IO biomarker • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • CD33 • MCL1 • TP53

Lintuzumab-Ac225, a CD33-Directed Antibody Radiotherapy, Targets AML in a Mutation Agnostic Manner (ASH 2023) - "Actimab-A, an anti-CD33 antibody conjugated with Actinium-225 (Ac-225) alpha particle-emitting radionuclide (lintuzumab-Ac225), has demonstrated promising therapeutic responses in AML patients, including in combination trials with chemotherapy regimen CLAG-M and targeted therapy venetoclax...Single agent cytotoxicity of Gilteritinib or Revumenib was also observed, but the combination of lintuzumab-Ac225 with FLT3 or MLL inhibitors was additive and synergistic at all dose levels studied...Combination of CD33-targeted radiation with either FLT3 or menin inhibitors significantly improves AML control, suggesting how FLT3 and/or menin efficacy may be augmented by radiation-induced DNA damage. The combination of lintuzumab-Ac225 to existing mutation-targeted standard-of-care may enhance AML targeting and treatment durability versus single-agent approaches."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • FLT3 • KMT2A

Lintuzumab-Ac225 Exerts Mutation Agnostic Antileukemic Activity in Preclinical Models of AML (ASH 2024) - "In clinical trials, lintuzumab-Ac225 has demonstrated promising therapeutic responses when added to CLAG-M chemotherapy in heavily pretreated relapsed/refractory AML patients, including high risk populations with venetoclax failures and TP53 mutations...Although the single agent cytotoxicity of FLT3 inhibitors (gilteritinib, quizartinib) and KMT2A inhibitors (revumenib, ziftomenib) was observed with varied sensitivity in both MV-4-11 and MOLM-13 FLT3/KMT2A mutation-carrying cells, the combinations with lintuzumab-Ac225 were additive at all studied dose levels (p<0.01)...CD33-targeted radiation-induced damage improves AML control in adverse-risk settings, and further potentiates response durability when added to standard-of-care, including molecularly targeted therapy. Collectively, these data support the backbone therapy potential of lintuzumab-Ac225 in a mutation agnostic manner, warranting further clinical evaluation in difficult to treat relapsed/refractory AML."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • CDKN1A • FLT3 • IDH1 • IDH2 • KMT2A • NPM1 • TP53

Testing an Anti-cancer Radio-Active Immunotherapy Called Lintuzumab Ac225 in Patients With High-Risk Myelodysplastic Syndrome That Has Not Responded to Other Treatment (clinicaltrials.gov) - P1 | N=30 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

Monotherapy • Trial suspension • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Testing the Combination of Targeted Radiotherapy With Anti-Cancer Drugs, Venetoclax and ASTX-727, to Improve Outcomes for Adults With Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=53 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2025 ➔ Dec 2028 | Initiation date: Jul 2025 ➔ Apr 2026 | Trial primary completion date: Sep 2025 ➔ Dec 2028

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Testing an Anti-cancer Radio-Active Immunotherapy Called Lintuzumab Ac225 in Patients With High-Risk Myelodysplastic Syndrome That Has Not Responded to Other Treatment (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Jul 2025 ➔ Apr 2026 | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Trial initiation date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Phase 1 study of lintuzumab-Ac225 combined with CLAG-M salvage therapy in relapsed/refractory acute myeloid leukemia. (PubMed, Leukemia) - "The composite complete remission (CRc) rates (CR/CRi) were 56.6% overall, 50% in patients with mutated TP53, and 38.5% in prior venetoclax-treated patients. Among all patients (n = 26), estimated 2-year OS was 23.1% (95% CI, 9.4-40.3) and estimated 1-year PFS was 30.8% (95% CI, 14.6-48.5). Lintuzumab-Ac225 plus CLAG-M was well tolerated with expected, manageable toxicities, while yielding deep and meaningful responses in high-risk R/R AML patients."

Journal • P1 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • TP53

Actinium Highlights Mutation Agnostic Antileukemic Activity of Actimab-A Against FLT3, NPM1, KMT2A and TP53 Mutations in AML Models Demonstrating Backbone Potential for Acute Myeloid Leukemia Treatment at the American Association for Cancer Research Annual Meeting (PRNewswire) - "The preclinical data demonstrate that the combination of Actimab-A with standard of care AML therapies including menin and FLT3 inhibitors and the hypomethylating agent (HMA) azacitidine resulted in significant antileukemic activity in AML cells lines with FLT3, NPM1, KMT2A and TP53 mutations. Additionally, in animal models, Actimab-A significantly enhanced tumor growth inhibition, prolonged the duration of response and survival when combined with the menin inhibitor revumenib (Syndax Pharmaceuticals, Inc.), and potentiated AML cell killing in combination with the FLT3 inhibitor gilteritinib (Astellas Pharma US, Inc.) and HMA azacitidine."

P53mut • Preclinical • Acute Myelogenous Leukemia

Lintuzumab-Ac225 has potent mutation agnostic antileukemic activity in preclinical models of AML (AACR 2025) - "In clinical trials, lintuzumab-Ac225 had positive responses when combined with CLAG-M chemotherapy in relapsed/refractory AML patients, including those with high-risk features like venetoclax resistance and TP53 mutations...FLT3 inhibitors (gilteritinib, quizartinib), KMT2A inhibitors (revumenib, ziftomenib) and azacitidine were evaluated as single agents and in combination with Lintuzumab-Ac225... Lintuzumab-Ac225 shows broad anti-leukemic activity in AML cell lines, in a mutation (FLT3, KMT2A, NPM1, TP53) agnostic manner. It improves AML control in high-risk cases and enhances response durability when combined with standard of care treatments. These findings support its potential as a backbone therapy for relapsed/refractory AML, warranting further clinical evaluation."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • CDKN1A • FLT3 • KMT2A • NPM1 • TP53

Actinium outlined its 2025 business objectives for its revitalized and expanding clinical pipeline as follows (PRNewswire) - "Establish In-house Radiopharmaceutical Manufacturing & Production: Advance build-out of manufacturing facility; Explore strategic partnerships leveraging proprietary Actinium-225 cyclotron manufacturing technology...Actimab-A as a mutation agnostic...Initiate additional clinical trials in myeloid malignancies....Actimab-A as a pan solid tumor therapy in combination with PD-1 inhibitors including KEYTRUDA and OPDIVO by depleting myeloid derived suppressor cells (MDSCs)...Explore additional solid tumor indications for future trials."

Commercial • New trial • Hematological Malignancies • Solid Tumor

Actinium Pharmaceuticals to Host KOL Investor Call at 8am ET Today to Highlight Revamped Clinical Programs and Expanded Market Opportunities Including Newly Initiated Actimab-A Solid Tumor Program (PRNewswire) - "Dr. Atallah will discuss Actimab-A clinical results to date including recently published long-term survival outcomes and the planned pivotal Phase 2/3 clinical trial in r/r AML and trials to be conducted under Actinium's cooperative research and development agreement (CRADA) with the National Cancer Institute (NCI). In addition, Actinium's management will detail its recently announced Actimab-A solid tumor program, which is comprised of several controlled, head-to-head clinical trials that will evaluate the combination of Actimab-A with KEYTRUDA versus KEYTRUDA alone, and Actimab-A with OPDIVO versus OPDIVO alone initially in patients with head and neck squamous cell carcinoma and non-small cell lung cancer with a separate trial for each indication....Actinium will present 3 separate multi-billion-dollar market opportunities for Actimab-A and Iomab-ACT in myeloid malignancies, solid tumors and cell & gene therapy conditioning."

Clinical • Clinical data • Commercial • Acute Myelogenous Leukemia • Solid Tumor

Actinium Pharmaceuticals Announces Supply Agreement with Eckert & Ziegler for Ac-225 Radioisotope to Support Comprehensive Development Activities (PRNewswire) - "Actinium Pharmaceuticals...announced it has entered into an agreement for the supply of Actinium-225 (Ac-225) with Eckert & Ziegler. Under this agreement, Actinium Pharmaceuticals will have access to Eckert & Ziegler's high-quality Actinium-225 to further develop its lead product Actimab-A as well as additional early and late-stage development candidates for both U.S. and international clinical trials....Actimab-A is an Ac-225 based radiotherapy agent, directed against CD33, a receptor overexpressed in patients with acute myeloid leukemia (AML) and other myeloid indications."

Licensing / partnership • Acute Myelogenous Leukemia

Actinium Pharmaceuticals Announces Publication of Actimab-A + CLAG-M Trial Results in Patients with Relapsed or Refractory Acute Myeloid Leukemia in the Peer-Reviewed Journal Leukemia (PRNewswire) - P1 | N=26 | NCT03441048 | "18.4 month median Overall Survival (OS) in patients who received 1 or 2 lines of prior therapy; 52% of patients in the Actimab-A +CLAG-M trial had TP53 mutations...Actimab-A + CLAG-M outcomes compare favorably to the results from historical data with CLAG-M alone in the pre-Venetoclax era from MCW's study (median OS of 13.3 months)...Actimab-A + CLAG-M produced high rates of measurable residual disease negativity (MRD-) including 75% across all patients, 83.3% in patients with a TP53 mutation and 100% in patients with prior Venetoclax.....Actinium has aligned with the FDA on a pivotal Phase 2/3 operationally seamless trial that will study Actimab-A + CLAG-M in r/r AML patients. The trial will optimize the dose of Actimab-A in combination with CLAG-M, that will be studied in the Phase 3 portion of the trial, which will be a randomized trial comparing overall survival and other outcomes of patients with r/r AML...The trial is expected to be initiated in 2025."

New P2/3 trial • P1 data • Acute Myelogenous Leukemia

Actinium Pharmaceuticals Announces Research Collaboration with Memorial Sloan Kettering to Support Further Clinical Expansion of Actimab-A's Backbone Therapy Strategy (PRNewswire) - "Actinium Pharmaceuticals, Inc...today announced that is has entered into a sponsored research agreement with Memorial Sloan Kettering Cancer Center (MSKCC) to expand Actimab-A's mutation agnostic mechanism of action. The collaboration has two specific objectives. The first objective is to study Actimab-A in combination with targeted therapies including FLT3 and menin inhibitors to define transcriptional profiles in AML cells following treatment with these combinations. The second objective is to assess the activity of Actimab-A-based combinations on primary AML patient-derived ex vivo samples from patients with and without prior Venetoclax + hypomethylating agent (HMA) treatment.... With recently initiated trials, this exciting research collaboration and clinical data expected in the second half of 2025, we believe we are making great progress to achieve our goal."

Clinical data • Licensing / partnership • Acute Myelogenous Leukemia

Testing an Anti-cancer Radio-Active Immunotherapy Called Lintuzumab Ac225 in Patients With High-Risk Myelodysplastic Syndrome That Has Not Responded to Other Treatment (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

Monotherapy • New P1 trial • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Actinium Pharmaceuticals Announces Initiation of Actimab-A Triplet Combination Frontline Trial Under NCI CRADA with Venetoclax and Taiho Oncology's Hypomethylating Agent ASTX-727 in Patients with Newly Diagnosed AML (PRNewswire) - "Actinium Pharmaceuticals, Inc...announced that the first clinical trial under its previously announced Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) for Actimab-A has been initiated. The trial (NCT06802523) will evaluate the triplet combination comprised of Actimab-A, Venetoclax (Abbvie/Roche) an oral Bcl-2 inhibitor and ASTX-727 (Taiho Oncology, an Otsuka holdings company) a novel oral hypomethylating agent (HMA) in frontline acute myeloid leukemia (AML) patients."

Trial status • Acute Myelogenous Leukemia

Actinium Pharmaceuticals to Host Investor KOL Call with Dr. Ehab Atallah of the Medical College of Wisconsin and Provide a Pipeline Update Highlighting Revamped Clinical Programs and Expanded Market Opportunities for Actimab-A and Iomab-ACT with Clinical Data in 2H:2025 (PRNewswire) - "Actimab-A expanded into frontline AML in triplet combination with Venetoclax and ASTX-727, Taiho Oncology's hypomethylating agent, under NCI CRADA with initial clinical data expected by year-end 2025...Iomab-ACT commercial CAR-T trial to initiate patient enrollment with clinical proof of concept data expected in 2H:2025...Dr. Atallah will discuss Actimab-A clinical results to date including recently published long-term survival outcomes and the planned pivotal Phase 2/3 clinical trial in r/r AML and trials to be conducted under Actinium's cooperative research and development agreement (CRADA) with the National Cancer Institute (NCI). In addition, Actinium will provide a pipeline update to highlight 3 separate potential multi-billion-dollar blockbuster market opportunities for its targeted radiotherapies..."

Commercial • P1 data • Trial status • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Oncology • Solid Tumor

Actinium Pharmaceuticals Announces Clinical Trial Program in Solid Tumors Combining Actimab-A with PD-1 Checkpoint Inhibitors KEYTRUDA and OPDIVO (PRNewswire) - "Actinium Pharmaceuticals, Inc...announced a clinical program comprising of trials studying Actimab-A in combination with either KEYTRUDA (pembrolizumab) or OPDIVO (nivolumab) which are blockbuster immunotherapies known as PD-1 inhibitors which are approved in multiple solid tumor indications....Actimab-A is under clinical development via an NCI CRADA in the front-line AML setting with an expected registrational study in combination with CLAG-M in relapsed/refractory AML expected to initiate in 2025. The Actimab-A solid tumor program is comprised of several controlled, head-to-head clinical trials that will evaluate the combination of Actimab-A with KEYTRUDA versus KEYTRUDA alone, and Actimab-A with OPDIVO versus OPDIVO alone....Actinium expects to present initial proof of concept clinical data from the first of these trials in the second half of 2025 as well as provide an update on the outlook for the rest of the trials in the Actimab-A solid tumor program."

Clinical data • New trial • Acute Myelogenous Leukemia • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Testing the Combination of Targeted Radiotherapy With Anti-Cancer Drugs, Venetoclax and ASTX-727, to Improve Outcomes for Adults With Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33

Actimab-A Regulatory and Development Update (PRNewswire) - "Actinium met with the FDA in the third quarter and aligned with the FDA on an operationally seamless randomized Phase 2/3 trial to study Actimab-A + CLAG-M; In the Phase 2 portion of the study, the Actimab-A dose will be optimized in combination with CLAG-M; The Phase 3 portion will study the optimized dose of Actimab-A + CLAG-M versus CLAG-M alone in patients with r/r AML; Operationally seamless trial design is expected to reduce the required time and resources compared to separate Phase 2 and Phase 3 trials....Actimab-A selected by NCI for recently opened myeloMATCH precision medicine program for patients with AML and myelodysplastic syndrome (MDS)."

New P2/3 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Actinium Provides Regulatory Update on Planned BLA Filing and Future Plans for Iomab-B in the U.S. (PRNewswire) - "Actinium will seek strategic partner for Iomab-B in the U.S. following completion of FDA interactions and focus development efforts on Actimab-A, Iomab-ACT and preclinical programs....Actinium Pharmaceuticals, Inc...announced a regulatory update on the Company's planned Biologics License Application ('BLA') filing for Iomab-B in patients with active relapsed or refractory acute myeloid leukemia ('r/r AML')....Despite the SIERRA trial meeting the primary endpoint of durable Complete Remission ('dCR') with statistical significance (p-value<0.0001) and other positive secondary endpoints including Event Free Survival ('EFS') and safety, the FDA has now determined that demonstrating an overall survival benefit in a randomized head-to-head trial is required for a BLA filing."

FDA event • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Actinium Pharmaceuticals to Present at the 3rd Annual Targeted Radiopharmaceuticals Summit US (PRNewswire) - "Actinium Pharmaceuticals, Inc...today announced that the Company will participate in the 3rd Annual Targeted Radiopharmaceuticals Summit US, being held in San Diego, CA, from July 30 – August 1, 2024...The presentation will highlight the following: Exploring Iomab-B, a CD45 I-131 ARC, to enable bone marrow transplant (BMT) in otherwise ineligible patients, while Actimab-A, a CD33 Ac-225 ARC, demonstrates strong anti-leukemic activity; Outlining responses in heavily pretreated patients for both Iomab-B and Actimab-A, including prior venetoclax treatment or TP53-mutated disease, to demonstrate how targeted radiotherapies offer broad therapeutic potential as backbone regimens; Revealing preclinical data to further show the benefits of combining Actimab-A with targeted therapies, such as FLT3 inhibitors, to enhance anti-tumor response."

Clinical data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

ANTILEUKEMIC ACTIVITY OF CD33-DIRECTED MUTATION-AGNOSTIC LINTUZUMAB-AC225 IN KMT2A MUTANT AML (EHA 2024) - "In clinical trials, the addition of lintuzumab-Ac225to chemotherapy regimen CLAG-M has shown substantial improvement in clinical outcomes in heavilypretreated relapsed/refractory AML patients, including venetoclax failures and those harboring TP53 mutations...Single agent cytotoxicity of revumenib and ziftomenib was also observed, but thecombination of lintuzumab-Ac225 with menin inhibitors potentiated the response at all dose levels studied(p<0... Our findings demonstrate that lintuzumab-Ac225 has potent anti-leukemic activity in AML cells harboringKMT2A genetic aberrations. Combination of CD33-targeted radionuclide therapy with menin inhibitorsignificantly improves AML control, demonstrating that targeted radiotherapy approaches can augment menin-targeted therapy. Based on these findings, the combination of lintuzumab-Ac225 with mutation-targetedagents may enhance anti-leukemic response compared to single-agent approaches."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD33 • KMT2A • TP53