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6ms
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)
11ms
Trial completion date • Combination therapy
|
CD33 positive
|
cytarabine • mitoxantrone • Actimab-A (lintuzumab-Ac225) • Depocyte (liposomal cytarabine)
1year
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)
1year
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)
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BCL2 expression • MCL1 expression • CD33 positive
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Venclexta (venetoclax) • Actimab-A (lintuzumab-Ac225)
1year
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
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FLT3 (Fms-related tyrosine kinase 3)
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FLT3 mutation
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Venclexta (venetoclax) • Xospata (gilteritinib) • Actimab-A (lintuzumab-Ac225)
1year
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
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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)
over1year
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
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CD33 (CD33 Molecule)
|
CD33 positive
|
Venclexta (venetoclax) • Actimab-A (lintuzumab-Ac225)
over1year
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
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CD33 (CD33 Molecule)
|
CD33 positive
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Venclexta (venetoclax) • azacitidine • Actimab-A (lintuzumab-Ac225)
over1year
Targeting myeloid-derived suppressor cells with actinium-225 lintuzumab, a CD33 antibody radioconjugate to enhance antitumor immunity (AACR 2023)
In this study, we demonstrate CD33 ARC alpha targeted radiotherapy depletes human CD33 positive immune suppressing MDSCs present in multiple cancer types, to enhance antitumor immunity. These findings present a translatable strategy that supports further evaluation of 225Ac lintuzumab as a MDSC targeting agent to improve the efficacy of antitumor therapies.
CD33 (CD33 Molecule) • CD34 (CD34 molecule)
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CD33 positive
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Actimab-A (lintuzumab-Ac225) • Zamyl (lintuzumab)
2years
Early Clinical Evaluation of Potential Synergy of Targeted Radiotherapy with Lintuzumab-Ac225 and Venetoclax in Relapsed/Refractory AML (ASH 2022)
Combining lintuzumab-Ac225 up to 1.5 µCi/kg with venetoclax in patients with R/R AML has an acceptable clinical safety profile with no mortality at day 30. The MTD, efficacious dose and dosing schedule of lintuzumab-Ac225 in combination with venetoclax is currently investigated in ongoing Phase I Cohort Expansion.
Clinical • IO biomarker
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TP53 (Tumor protein P53) • BCL2L1 (BCL2-like 1) • CD33 (CD33 Molecule)
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TP53 mutation • BCL2 expression • MCL1 expression • CD33 positive
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Venclexta (venetoclax) • Actimab-A (lintuzumab-Ac225)
2years
Lintuzumab-Ac225 with Combination with Intensive Chemotherapy Yields High Response Rate and MRD Negativity in R/R AML with Adverse Features (ASH 2022)
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. Actimab-A at 0.75uCi/kg, combined with CLAG-M is feasible and safe, and this combination demonstrates a high response rate and MRD negativity in a high-risk AML population. Pharmacokinetics at the RP2D indicate rapid drug clearance. Furthermore, responses appear durable, particularly among patients who are able to proceed to alloHCT.
Minimal residual disease
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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
Where do we stand with radioimmunotherapy for acute myeloid leukemia? (PubMed, Expert Opin Biol Ther)
An I-labeled CD45 antibody (Iomab-B [apamistamab-I131]) is currently studied in the registration-type phase 3 SIERRA trial (NCT02665065) for this purpose...Clinical efforts with At-labeled CD45 antibodies and Ac-labeled CD33 antibodies (e.g. Ac-lintuzumab [Actimab-A]) are ongoing. A first anti-AML RIT may soon become available. This might propel further work to develop RIT-based treatments for AML, with many such efforts already ongoing.
Journal
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CD33 (CD33 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C)
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Actimab-A (lintuzumab-Ac225) • Iomab-B (I-131-apamistamab) • Zamyl (lintuzumab)
over2years
Lintuzumab-Ac225 in Older Acute Myeloid Leukemia (AML) Patients (clinicaltrials.gov)
P1/2, N=40, Completed, Actinium Pharmaceuticals | Active, not recruiting --> Completed | N=72 --> 40
Trial completion • Enrollment change
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CD33 (CD33 Molecule)
|
CD33 positive
|
cytarabine • Actimab-A (lintuzumab-Ac225)
over2years
A Phase I Study of Lintuzumab-Ac225 in Patients With Refractory Multiple Myeloma (clinicaltrials.gov)
P1, N=2, Terminated, Actinium Pharmaceuticals | N=12 --> 2 | Active, not recruiting --> Terminated; Poor recruitment
Enrollment change • Trial termination
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CD33 (CD33 Molecule)
|
CD33 positive
|
Actimab-A (lintuzumab-Ac225)
over2years
Venetoclax and Lintuzumab-Ac225 in AML Patients (clinicaltrials.gov)
P1/2, N=38, Recruiting, Actinium Pharmaceuticals | Trial primary completion date: Jan 2021 --> Dec 2022
Trial primary completion date
|
CD33 (CD33 Molecule)
|
CD33 positive
|
Venclexta (venetoclax) • Actimab-A (lintuzumab-Ac225)
almost3years
Venetoclax, Azacitidine, and Lintuzumab-Ac225 in AML Patients (clinicaltrials.gov)
P1/2, N=38, Not yet recruiting, Actinium Pharmaceuticals | Trial primary completion date: Sep 2022 --> Dec 2023
Trial primary completion date
|
CD33 (CD33 Molecule)
|
CD33 positive
|
Venclexta (venetoclax) • azacitidine • Actimab-A (lintuzumab-Ac225)
3years
Lintuzumab-Ac225 in Combination with CLAG-M Yields High MRD (-) Responses in R/R AML with Adverse Features: Interim Results of a Phase I Study (ASH 2021)
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. Lintuzumab-Ac225 at a low dose appears to be safe in combination with the salvage chemotherapy regimen CLAG-M. Furthermore, this combination has demonstrated promising efficacy results among high risk RR-AML patients, namely patients with adverse molecular/cytogenetic features and patients previously receiving venetoclax. Updated Cohort 4 results will be presented at ASH.
P1 data • Combination therapy
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TP53 (Tumor protein P53) • CD33 (CD33 Molecule)
|
TP53 mutation • CD33 expression
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Venclexta (venetoclax) • cytarabine • mitoxantrone • cladribine • Actimab-A (lintuzumab-Ac225)
3years
Early Clinical Evaluation of Potential Synergy of Targeted Radiotherapy with Lintuzumab-Ac225 and Venetoclax in Relapsed/Refractory AML (ASH 2021)
Combining lintuzumab-Ac225 with venetoclax in patients with R/R AML has an acceptable clinical safety profile with 0% 30-day mortality rate. 67% ORR is particularly encouraging in TP53 -mutant R/R AML. These data support the further evaluation of lintuzumab-Ac225 in combination with venetoclax in patients with R/R AML, especially in TP53 -mutant R/R patients.
Clinical • IO biomarker
|
TP53 (Tumor protein P53) • BCL2L1 (BCL2-like 1) • CD33 (CD33 Molecule)
|
TP53 mutation • BCL2 expression • MCL1 expression • CD33 positive
|
Venclexta (venetoclax) • Actimab-A (lintuzumab-Ac225)
almost4years
225Ac-labeled CD33-targeting antibody reverses resistance to Bcl-2 inhibitor venetoclax in acute myeloid leukemia models. (PubMed, Cancer Med)
There results suggest that the combination of Ac-lintuzumab with venetoclax is a promising therapeutic strategy for the treatment of patients with venetoclax-resistant AML. Clinical trial of this combination therapy (NCT03867682) is currently ongoing.
Journal
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MCL1 (Myeloid cell leukemia 1) • CD33 (CD33 Molecule)
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MCL1 expression
|
Venclexta (venetoclax) • cytarabine • Actimab-A (lintuzumab-Ac225) • Zamyl (lintuzumab)
4years
Lintuzumab-Ac225 in Older Acute Myeloid Leukemia (AML) Patients (clinicaltrials.gov)
P1/2, N=72, Active, not recruiting, Actinium Pharmaceuticals | Trial completion date: Dec 2020 --> Mar 2021 | Trial primary completion date: Jun 2020 --> Dec 2020
Clinical • Trial completion date • Trial primary completion date
|
CD33 (CD33 Molecule)
|
CD33 positive
|
cytarabine • Actimab-A (lintuzumab-Ac225)