A Phase IIB, Randomized, Double-Blinded, Placebo-Controlled Study of Low Dose Cytarabine and Lintuzumab Compared to Low Dose Cytarabine and Placebo in Patients 60 Years of Age and Older with Previously Untreated AML.

Start Date30 Jul 2008

Sponsor / Collaborator

Seagen Inc.

NCT00006045 / Unknown statusPhase 3

Phase III, Randomized, Multicenter Study to Assess the Efficacy and Safety of HuM195 (Recombinant Humanized Anti-CD33 Monoclonal Antibody) in Combination With Standardized Chemotherapy Compared to Standardized Chemotherapy Alone in the Treatment of Patients With Refractory or First-Relapsed Acute Myelogenous Leukemia (AML)

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known if chemotherapy is more effective with or without monoclonal antibody therapy for acute myelogenous leukemia.
PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without monoclonal antibody therapy in treating patients who have refractory or relapsed acute myelogenous leukemia.

Start Date01 Mar 2000

Sponsor / Collaborator

Abbott Biotherapeutics Corp.

[+1]

NCT00038051 / CompletedPhase 1IIT

Phase I Evaluation of the Anti-CD-33 Immunotoxin Hum-195/rGel in Patients With Advanced Myeloid Malignancies

The goal of this clinical research study is to find the highest safe dose of the anti-CD33 immunotoxin HuM-195/rGel that can be given to patients with advanced myeloid malignancies. This treatment will be given to patients whose leukemia has not responded to prior chemotherapy.

Start Date01 May 1999

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

100 Clinical Results associated with Lintuzumab

100 Translational Medicine associated with Lintuzumab

100 Patents (Medical) associated with Lintuzumab

206

Literatures (Medical) associated with Lintuzumab

01 Aug 2024·Molecular Cancer Therapeutics

Targeting CD33+ Acute Myeloid Leukemia with GLK-33, a Lintuzumab–Auristatin Conjugate with a Wide Therapeutic Window

Article

Author: Niemelä, Ritva ; Kontro, Mika ; Yatkin, Emrah ; Kotiranta, Titta ; Rathod, Ramji ; Pynnönen, Henna ; Helin, Jari ; Kuusanmäki, Heikki ; Satomaa, Tero ; Nieminen, Anni I. ; Lähteenmäki, Tuula ; Hänninen, Anna-Liisa ; Heckman, Caroline A. ; Hiltunen, Jukka O. ; Saarinen, Juhani ; Aitio, Olli ; Vänttinen, Ida ; Heiskanen, Annamari ; Pitkänen, Virve

AbstractCD33 (Siglec-3) is a cell surface receptor expressed in approximately 90% of acute myeloid leukemia (AML) blasts, making it an attractive target for therapy of AML. Although previous CD33-targeting antibody–drug conjugates (ADC) like gemtuzumab ozogamicin (GO, Mylotarg) have shown efficacy in AML treatment, they have suffered from toxicity and narrow therapeutic window. This study aimed to develop a novelADCwith improved tolerability and a wider therapeutic window. GLK-33 consists of the anti-CD33 antibody lintuzumab and eight mavg-MMAU auristatin linkerpayloads per antibody. The experimental methods included testing in cell cultures, patient-derived samples, mouse xenograft models, and rat toxicology studies. GLK-33 exhibited remarkable efficacy in reducing cell viability within CD33-positive leukemia cell lines and primary AML samples. Notably, GLK-33 demonstrated antitumor activity at single dose as low as 300 mg/kg in mice, while maintaining tolerability at single dose of 20 to 30 mg/kg in rats. In contrast with both GO and lintuzumab vedotin, GLK-33 exhibited a wide therapeutic window and activity against multidrug-resistant cells. The development of GLK-33 addresses the limitations of previous ADCs, offering a wider therapeutic window, improved tolerability, and activity against drug-resistant leukemia cells. These findings encourage further exploration of GLK-33 in AML through clinical trials.

01 Aug 2024·Bone Marrow Transplantation

Azacitidine and gemtuzumab ozogamicin as post-transplant maintenance therapy for high-risk hematologic malignancies

Article

Author: Kobayashi, Takeshi ; Toya, Takashi ; Shingai, Naoki ; Nagata, Akihito ; Kishida, Yuya ; Kaito, Satoshi ; Konishi, Tatsuya ; Hirama, Chizuko ; Doki, Noriko ; Yoshifuji, Kota ; Yamada, Yuta ; Shimizu, Hiroaki ; Okuyama, Yoshiki ; Najima, Yuho ; Haraguchi, Kyoko ; Harada, Yuka ; Kurosawa, Shuhei ; Harada, Hironori ; Sadato, Daichi ; Shirane, Shuichi

Disease recurrence remains the principal cause of treatment failure after allogeneic hematopoietic stem cell transplantation. Post-transplant maintenance therapy with azacitidine (AZA) is promising to prevent relapse but the outcomes are unsatisfactory in patients at high risk of recurrence. Herein, we evaluated the outcome in patients who received AZA and gemtuzumab ozogamicin (GO), anti-CD33 antibody-calicheamicin conjugate, as post-transplant maintenance therapy. Twenty-eight patients with high-risk hematologic malignancies harboring CD33-positive leukemic blasts received the maintenance therapy. AZA (30 mg/m²) was administered for 7 days, followed by GO (3 mg/m²) on day 8. The maximum number of cycles was 4. At transplant, 21 patients (75.0%) had active disease. Their 2-year overall survival, disease-free survival, relapse, and non-relapse mortality rates were 53.6%, 39.3%, 50.0%, and 10.7%, respectively. Of these patients, those with minimal residual disease at the start of maintenance therapy (n = 9) had a higher recurrence rate (66.7% vs. 42.1% at 2 years, P = 0.069) and shorter disease-free survival (11.1% vs. 52.6% at 2 years, P = 0.003). Post-transplant maintenance therapy with AZA and GO was generally tolerable but more than half of the patients eventually relapsed. Further improvements are needed to prevent relapse after transplantation in patients with high-risk hematologic malignancies.

01 Jul 2024·Molecular Psychiatry

HuM195 and its single-chain variable fragment increase Aβ phagocytosis in microglia via elimination of CD33 inhibitory signaling

Article

Author: Studer, Lorenz ; Kehs, Zoe ; Liao, George P ; Jain, Tanya ; Li, Yue-Ming ; Scheinberg, David A ; Chang, Jerry C ; Malviya, Manish ; Wong, Eitan

CD33 is a transmembrane receptor expressed on cells of myeloid lineage and regulates innate immunity. CD33 is a risk factor for Alzheimer's disease (AD) and targeting CD33 has been a promising strategy drug development. However, the mechanism of CD33's action is poorly understood. Here we investigate the mechanism of anti-CD33 antibody HuM195 (Lintuzumab) and its single-chain variable fragment (scFv) and examine their therapeutic potential. Treatment with HuM195 full-length antibody or its scFv increased phagocytosis of β-amyloid 42 (Aβ42) in human microglia and monocytes. This activation of phagocytosis was driven by internalization and degradation of CD33, thereby downregulating its inhibitory signal. HumM195 transiently induced CD33 phosphorylation and its signaling via receptor dimerization. However, this signaling decayed with degradation of CD33. scFv binding to CD33 leads to a degradation of CD33 without detection of the CD33 dimerization and signaling. Moreover, we found that treatments with either HuM195 or scFv promotes the secretion of IL33, a cytokine implicated in microglia reprogramming. Importantly, recombinant IL33 potentiates the uptake of Aβ42 in monocytes. Collectively, our findings provide unanticipated mechanistic insight into the role of CD33 signaling in both monocytes and microglia and define a molecular basis for the development of CD33-based therapy of AD.

News (Medical) associated with Lintuzumab

28 Nov 2023

·www.biospace.com

BMS Expands Cardio Partnership with Avidity in Potential $2.3B Deal

Pictured: Bristol Myers Squibb building in Munich/iStock, Tati Campelo Bristol Myers Squibb is upping the ante in its partnership with Avidity Biosciences. The San Diego-based biopharma announced Tuesday an expansion of its previous collaboration with BMS, with the latter paying $100 million upfront and adding up to five cardiovascular targets. With potential cumulative payments of up to $2.3 billion plus low double-digit royalties, the partnership could be a lucrative one for the RNA biopharma. The deal expansion sent Avidity’s suffering stock soaring around 35% in premarket trading. A welcome reprieve to the 72% tumble it took earlier this year. Avidity will get a $60 million upfront cash payment in addition to BMS scooping up $40 million of its stock to deliver new cardiovascular treatments utilizing the former’s antibody oligonucleotide conjugates (AOCs). Avidity’s AOCs combine the targeting specificity of monoclonal antibodies with the precision of oligonucleotide therapies to treat diseases RNA therapeutics couldn’t reach before, according to the company. “This collaboration with Avidity represents an important part of our continued investment in innovative therapeutic approaches that have the potential to provide transformative outcomes to patients living with serious cardiovascular conditions,” Francisco Ramírez-Valle, head of BMS cardiovascular thematic research, said in a statement. The deal builds on a previous collaboration between Avidity and MyoKardia, a subsidiary of BMS. In 2021, the two announced a research partnership to demonstrate AOC efficacy in cardiac tissue, broadening beyond its use in skeletal muscle. Avidity is a clinical stage biopharma with three candidates in early-stage trials for types of muscular dystrophy as well as additional assets in lead optimization for rare skeletal muscle and rare cardiac diseases. The company’s lead candidate for muscle wasting disorder was subject to an FDA clinical hold in September 2022, which has since been changed to a partial clinical hold. With the Avidity deal, BMS continues its spending spree. Despite pushing back 2023’s target sales due to a third-quarter revenue decline, the pharma giant has been recently dropping money on deals. Earlier this month, BMS paid $100 million upfront to Orum Therapeutics for the company’s anti-CD33 antibody enabled GSPT1 degrader that aims to treat patients with acute myeloid leukemia. In October 2023, BMS announced a merger agreement with Mirati Therapeutics paying $4.8 billion for its oncology franchise. The company also expanded its manufacturing agreement with Samsung Biologics for an unnamed cancer antibody in a deal worth $242 million in September 2023. Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.

AcquisitionOligonucleotide

06 Nov 2023

·www.prnewswire.com

Actinium Presents Preclinical Data at SITC Demonstrating Actimab-A's Potential to Restore T Cell Immunity in the Solid Tumor Microenvironment Supporting Immunotherapy Combinations

Actimab-A can target CD33 positive immune suppressing myeloid derived suppressor cells and restore T cell proliferation and effector response Solid tumor MDSC infiltration and uptake of Actimab-A confirmed by SPECT/CT imaging in a humanized non-small cell lung cancer model NEW YORK, Nov. 6, 2023 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, today announced data was presented at Society of Immunotherapy of Cancer (SITC) 38th Annual Meeting on Saturday, November 4, 2023, further supporting Actimab-A, the Company's clinical stage targeted radiotherapeutic comprised of the CD33 targeting antibody lintuzumab and the Actinium-225 (Ac-225) alpha-particle emitting payload. The poster highlighted Actimab-A's ability to target and deplete myeloid-derived suppressor cells (MDSCs), which uniformly express CD33. MDSCs are a cell population of interest as they remodel the tumor environment and promote immune evasion. Actinium believes Actimab-A has the potential to be used in combination with immunotherapy, including immune checkpoint inhibitors, to enhance antitumor immunity via targeted MDSC depletion. Supportive data from the SITC presentation includes: Actimab-A reduced cancer patient-derived MDSCs in a dose-dependent manner ex vivo and decreased MDSC viability approximately two-fold greater than a non-radiolabeled CD33 antibody MDSC suppression of activated T cell proliferation and cytokine effector function ex vivo was restored following treatment with Actimab-A Actimab-A significantly depleted MDSCs in peripheral blood of tumor-bearing humanized mice compared to non-radiolabeled CD33 antibody in vivo SPECT/CT imaging confirmed uptake of lintuzumab in humanized mice at the sites of non-small cell lung cancer tumor indicating enrichment of CD33+ MDSCs in the tumor microenvironment Sandesh Seth, Actinium's Chairman and CEO, commented, "These data further increase our enthusiasm for Actimab-A's potential in solid tumor indications. Immunotherapy has had a profound impact on patient outcomes across multiple solid tumor indications, however, there are still several indications with high unmet needs and significant room to further improve patient outcomes. By depleting MDSCs in a targeted manner, we are excited by the prospect of Actimab-A synergizing with immunotherapy to enhance antitumor immunity. We look forward to continuing to advance this initiative in continuing our goal to address high unmet patient needs with our targeted radiotherapeutics." About Actinium Actinium develops targeted radiotherapies to meaningfully improve survival for people who have failed existing oncology therapies. Advanced pipeline candidates Iomab-B (pre-BLA), an induction and conditioning agent prior to bone marrow transplant, and Actimab-A (National Cancer Institute CRADA pivotal development path), a therapeutic, have demonstrated potential to extend survival outcomes for people with relapsed and refractory acute myeloid leukemia. Actinium plans to advance Iomab-B for other blood cancers and next generation conditioning candidate Iomab-ACT to improve cell and gene therapy outcomes. Actinium's technology platform is the basis for collaborations with Astellas Pharma and AVEO Oncology/LG Chem Life Sciences for solid tumors. Actinium holds more than 220 patents and patent applications. For more information, please visit: Forward-Looking Statements 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. Contact: [email protected] SOURCE Actinium Pharmaceuticals, Inc.

Immunotherapy

27 Sep 2023

·www.biospace.com

Actinium Pharma Highlights Abstract Accepted for Poster Presentation at the SITC 38th Annual Meeting

[27-September-2023] NEW YORK, Sept. 27, 2023 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, today details an abstract accepted for poster presentation at the upcoming Society of Immunotherapy of Cancer (SITC) 38th Annual Meeting, which will be held in San Diego, November 3-5, 2023. Details of the SITC poster presentation: Abstract Title: Preclinical evaluation of lintuzumab-Ac225, a CD33 antibody radioconjugate targeting myeloid-derived suppressor cells Abstract Number: 1166 Session: November 4, 9:00 AM – 8:30 PM PT, Exhibit Halls A and B1 About Actinium Actinium develops targeted radiotherapies to meaningfully improve survival for people who have failed existing oncology therapies. Advanced pipeline candidates Iomab-B (pre-BLA), an induction and conditioning agent prior to bone marrow transplant, and Actimab-A (National Cancer Institute CRADA pivotal development path), a therapeutic, have demonstrated potential to extend survival outcomes for people with relapsed and refractory acute myeloid leukemia. Actinium plans to advance Iomab-B for other blood cancers and next generation conditioning candidate Iomab-ACT to improve cell and gene therapy outcomes. Actinium's technology platform is the basis for collaborations with Astellas Pharma for solid tumors, AVEO Oncology/LG Chem Life Sciences for HER3 solid tumors, and EpicentRx for its CD47 targeting agent, and several internal programs in solid tumors. Actinium holds more than 200 patents and patent applications. For more information, please visit: Forward-Looking Statements 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. Contact: Matthew Beck Vice President Investor Relations & Communications mbeck@actiniumpharma.com (917) 415-1750 Company Codes: AMEX:ATNM, NYSE:NYSE, AMEX:NYSE

Immunotherapy

100 Deals associated with Lintuzumab

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Myelodysplastic Syndromes	Phase 3	US	Seagen Inc.	01 Nov 2009
Leukemia	Phase 3	DE	Abbott Biotherapeutics Corp.	01 Mar 2000
Leukemia	Phase 3	FR	Abbott Biotherapeutics Corp.	01 Mar 2000
Leukemia	Phase 3	NL	Abbott Biotherapeutics Corp.	01 Mar 2000
Leukemia	Phase 3	US	Abbott Biotherapeutics Corp.	01 Mar 2000
Leukemia	Phase 3	BE	Abbott Biotherapeutics Corp.	01 Mar 2000
Leukemia	Phase 3	CA	Abbott Biotherapeutics Corp.	01 Mar 2000
Leukemia	Phase 3	GB	Abbott Biotherapeutics Corp.	01 Mar 2000
Acute Myeloid Leukemia	Phase 3	-	PDL BioPharma, Inc.	-
Acute Myeloid Leukemia	Phase 3	-	PDL BioPharma, Inc.	-

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