^
    2d
    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, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension
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    Venclexta (venetoclax) • Inqovi (decitabine/cedazuridine) • Actimab-A (lintuzumab-Ac225)
    10ms
    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.
    P1 data • Journal
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    TP53 (Tumor protein P53)
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    TP53 mutation
    |
    Venclexta (venetoclax) • Actimab-A (lintuzumab-Ac225)
    11ms
    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, National Cancer Institute (NCI)
    New P1 trial
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    CD33 (CD33 Molecule)
    |
    Venclexta (venetoclax) • Inqovi (decitabine/cedazuridine) • Actimab-A (lintuzumab-Ac225)
    over1year
    Lintuzumab-Ac225 in Combination With Cladribine + Cytarabine + Filgastrim + Mitoxantrone (CLAG-M) for Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=26, Completed, Medical College of Wisconsin | Active, not recruiting --> Completed | Trial completion date: Oct 2024 --> May 2024
    Trial completion • Trial completion date • Combination therapy
    |
    cytarabine • mitoxantrone • Actimab-A (lintuzumab-Ac225) • Depocyte (liposomal cytarabine)
    almost2years
    Lintuzumab-Ac225 in Combination With Cladribine + Cytarabine + Filgastrim + Mitoxantrone (CLAG-M) for Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=26, Active, not recruiting, Medical College of Wisconsin
    Trial completion date • Combination therapy
    |
    CD33 positive
    |
    cytarabine • mitoxantrone • Actimab-A (lintuzumab-Ac225) • Depocyte (liposomal cytarabine)
    2years
    Lintuzumab-Ac225 in Combination With Cladribine + Cytarabine + Filgastrim + Mitoxantrone (CLAG-M) for Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=26, Active, not recruiting, Medical College of Wisconsin | Trial primary completion date: Oct 2024 --> May 2024
    Trial primary completion date • Combination therapy
    |
    CD33 positive
    |
    cytarabine • mitoxantrone • Actimab-A (lintuzumab-Ac225) • Depocyte (liposomal cytarabine)
    2years
    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.
    P1 data • Combination therapy • IO biomarker
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    BCL2L1 (BCL2-like 1) • CD33 (CD33 Molecule)
    |
    BCL2 expression • MCL1 expression • CD33 positive
    |
    Venclexta (venetoclax) • Actimab-A (lintuzumab-Ac225)
    over2years
    Antileukemic Activity of Lintuzumab‑Ac225 in Preclinical Model of FLT3 Mutant AML (SOHO 2023)
    We have demonstrated promising therapeutic responses with Actimab-A (lintuzumab- Ac225, an anti-CD33 antibody conjugated with actinium-225) in patients with AML, including in combination trials with chemotherapy regimen CLAG-M and targeted therapy venetoclax...Objective: In this study, we evaluated the antileukemic activity of lintuzumab-Ac225 in FLT3 mutant AML as a single agent and in combination with the FLT3- targeted inhibitor gilteritinib... Our findings show that single-agent lintuzumab-Ac225 has potent antileukemic activity against FLT3 mutant AML and can significantly improve the effect of FLT3 inhibitors in combination. Based on these results, lintuzumab-Ac225 may potentially provide new combination therapy for patients with FLT3 mutant AML.
    Preclinical
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3 mutation
    |
    Venclexta (venetoclax) • Xospata (gilteritinib) • Actimab-A (lintuzumab-Ac225)
    over2years
    Sequential Salvage Chemotherapy and Lintuzumab‑Ac225 in Relapsed/ Refractory AML Results in Deep Responses and Prolonged Survival in Adverse Risk Acute Myeloid Leukemia (AML) and in AML Patients that Received Prior Venetoclax Therapy (SOHO 2023)
    Induction consisted of G-CSF, 300mcg/d, given D1-6, cladribine 5mg/m2, given D2-6, cytarabine 2g/m2, given D2-6, and mitoxantrone 10mg/m2, given D2-4. CLAG-M followed by Lintuzumab-Ac225 yielded significantly better clinical outcomes in high-risk populations, particularly in patients previously treated with venetoclax combinations. The results further support the late-stage clinical development of Lintuzumab-Ac225 in combination with CLAG-M in R/R AML.
    Clinical
    |
    TP53 (Tumor protein P53) • MCL1 (Myeloid cell leukemia 1) • CD33 (CD33 Molecule)
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    TP53 mutation • CD33 expression
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    Venclexta (venetoclax) • cytarabine • mitoxantrone • cladribine • Actimab-A (lintuzumab-Ac225)
    over2years
    Venetoclax and Lintuzumab-Ac225 in AML Patients (clinicaltrials.gov)
    P1/2, N=38, Recruiting, Actinium Pharmaceuticals | Trial completion date: Jan 2023 --> Jun 2024 | Trial primary completion date: Dec 2022 --> Nov 2023
    Trial completion date • Trial primary completion date
    |
    CD33 (CD33 Molecule)
    |
    CD33 positive
    |
    Venclexta (venetoclax) • Actimab-A (lintuzumab-Ac225)
    over2years
    Venetoclax, Azacitidine, and Lintuzumab-Ac225 in AML Patients (clinicaltrials.gov)
    P1/2, N=0, Withdrawn, Actinium Pharmaceuticals | N=38 --> 0 | Not yet recruiting --> Withdrawn
    Enrollment change • Trial withdrawal
    |
    CD33 (CD33 Molecule)
    |
    CD33 positive
    |
    Venclexta (venetoclax) • azacitidine • Actimab-A (lintuzumab-Ac225)