Phase I study of anti‐<scp>CD</scp>22 immunoconjugate inotuzumab ozogamicin plus rituximab in relapsed/refractory <scp>B</scp>‐cell non‐<scp>H</scp>odgkin lymphoma

Ogura, Michinori; Hatake, Kiyohiko; Ando, Kiyoshi; Tobinai, Kensei; Tokushige, Kota; Ono, Chiho; Ishibashi, Tomoko; Vandendries, Erik

doi:10.1111/j.1349-7006.2012.02241.x

Cited by 58 publications

(41 citation statements)

References 18 publications

(49 reference statements)

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“…Other common toxicities resulting from this combination included hyperbilirubinemia (25%) and increased aspartate aminotransferase (36%). As reported previously by Ogura et al in Japanese patients, the MTD of inotuzumab ozogamicin with co-administered rituximab at 375 mg/m 2 was consistent with the MTD of single-agent inotuzumab ozogamicin at 1.8 mg/m 2 [86, 87]. Treatment at this dose achieved overall response rates of 87, 74, and 20% for follicular lymphoma, DLBCL, and NHL, respectively.…”

Section: Inotuzumab Ozogamicinsupporting

confidence: 86%

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Antibody–Drug Conjugates: Pharmacokinetic/Pharmacodynamic Modeling, Preclinical Characterization, Clinical Studies, and Lessons Learned

et al. 2017

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Antibody–drug conjugates are an emerging class of biopharmaceuticals changing the landscape of targeted chemotherapy. These conjugates combine the target specificity of monoclonal antibodies with the anti-cancer activity of small-molecule therapeutics. Several antibody–drug conjugates have received approval for the treatment of various types of cancer including gemtuzumab ozogamicin (Mylotarg®), brentuximab vedotin (Adcetris®), trastuzumab emtansine (Kadcyla®), and inotuzumab ozogamicin, which recently received approval (Besponsa®). In addition to these approved therapies, there are many antibody–drug conjugates in the drug development pipeline and in clinical trials, although these fall outside the scope of this article. Understanding the pharmacokinetics and pharmacodynamics of antibody–drug conjugates and the development of pharmacokinetic/pharmacodynamic models is indispensable, albeit challenging as there are many parameters to incorporate including the disposition of the intact antibody–drug conjugate complex, the antibody, and the drug agents following their dissociation in the body. In this review, we discuss how antibody–drug conjugates progressed over time, the challenges in their development, and how our understanding of their pharmacokinetics/pharmacodynamics led to greater strides towards successful targeted therapy programs.

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Section: Inotuzumab Ozogamicinsupporting

confidence: 86%

“…The reported overall response rate with this combination was 80% (eight of ten patients). Exposure to the conjugated drug increased with successive doses, similar to the observed PK profiles observed in preliminary studies with inotuzumab ozogamicin monotherapy [86, 87]. …”

Section: Inotuzumab Ozogamicinsupporting

confidence: 71%

Antibody–Drug Conjugates: Pharmacokinetic/Pharmacodynamic Modeling, Preclinical Characterization, Clinical Studies, and Lessons Learned

et al. 2017

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“…Because many siglecs are endocytic receptors (Shan & Press, 1995; Crocker et al, 2007), immunotoxins have been adopted as an attractive clinical strategy since binding of the antibody to CD22 and CD33 results in endocytosis of the complex, delivering the toxin into the cell. Immunotoxins targeting both CD22 and CD33 continue to be actively pursued in clinical trials for lymphomas and leukemias expressing these siglecs (Kreitman & Pastan, 2006; Tu et al, 2011; Jurcic, 2012; Kreitman et al, 2012; Ogura et al, 2012; Pollard et al, 2012; Walter et al, 2012). B cell depletion strategies using CD22 antibodies are also being pursued for treatment of a number of autoimmune diseases (Dunussi-Joannopoulos et al, 2005; Leonard & Goldenberg, 2007; Fiorina et al, 2008).…”

Section: Prospects For Therapeutic Applications Of Targeting Siglementioning

confidence: 99%

Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions

Kiwamoto

Kawasaki

Paulson

et al. 2012

Pharmacology & Therapeutics

164

130

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Siglecs (sialic acid immunoglobulin-like lectins) are members of the immunoglobulin gene family that contain sialoside binding N-terminal domains. They are cell surface proteins found predominantly on cells of the immune system. Among them, Siglec-8 is uniquely expressed by human eosinophils and mast cells, as well as basophils. Engaging this structure with antibodies or glycan ligands results in apoptosis in human eosinophils and inhibition of release of preformed and newly generated mediators from human mast cells without affecting their survival. Pro-apoptotic effects are also seen when its closest functional paralog, Siglec-F, on mouse eosinophils is similarly engaged in vitro, and beneficial effects are observed after administration of Siglec-F antibody using models of eosinophilic pulmonary and gastrointestinal inflammation in vivo. Siglec-8 targeting may thus provide a means to specifically inhibit or deplete these cell types. Cell-directed therapies are increasingly sought after by the pharmaceutical industry for their potential to reduce side effects and increase safety. The challenge is to identify suitable targets on the cell type of interest, and selectively deliver a therapeutic agent. By targeting Siglec-8, monoclonal antibodies and glycan ligand-conjugated nanoparticles may be ideally suited for treatment of eosinophil and mast cell-related diseases, such as asthma, chronic rhinosinusitis, chronic urticaria, hypereosinophilic syndromes, mast cell and eosinophil malignancies and eosinophilic gastrointestinal disorders.

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“…The most common grade ≥3 side effects were thrombocytopenia (70 %), neutropenia (50 %), leukopenia (30 %), and lymphopenia (30 %). The ORR was 80 % (8 of 10; 95 % CI, 44-98) (NTC01055496) [36]. In a phase II study in patients with relapse/refractory ALL, INO resulted in an ORR of 57 % (CR, 18 %) (NTC01134575) [37].…”

Section: Inotuzumab Ozogamicin (Cmc-544 Pfizer)mentioning

confidence: 97%

Development and Integration of Antibody–Drug Conjugate in Non-Hodgkin Lymphoma

Mehta

Forero‐Torres

2015

Curr Oncol Rep

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Rituximab, a monoclonal antibody (MAb) against CD20, was the first MAb approved by the US Food and Drug Administration (FDA) for treatment of B cell non-Hodgkin lymphoma (B-NHL). Conjugating toxins to MAb was a technical challenge; however, with improvements in linker technology, immunoconjugates were constructed and revolutionized cancer treatment. Gemtuzumab ozogamicin was the first antibody drug conjugate (ADC) approved by the FDA. Because of the success of brentuximab vedotin and ado-trastuzumab emtansine in treating Hodgkin lymphoma (HL) and HER2-positive breast cancer, respectively, newer ADCs are being investigated. Brentuximab vedotin is approved for both HL and anaplastic large cell lymphoma. Newer ADCs, such as polatuzumab vedotin (targeting CD79b), pinatuzumab vedotin (targeting CD22), inotuzumab ozogamicin (targeting CD19), SAR3419 (targeting CD19), IMGN529 (targeting CD37), and SGN-CD19A (targeting CD19), have shown promising preclinical and early clinical activity. These findings will change the landscape of B-NHL treatment away from age-old "CHOP"-based chemotherapies.

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Phase I study of anti‐CD22 immunoconjugate inotuzumab ozogamicin plus rituximab in relapsed/refractory B‐cell non‐Hodgkin lymphoma

Cited by 58 publications

References 18 publications

Antibody–Drug Conjugates: Pharmacokinetic/Pharmacodynamic Modeling, Preclinical Characterization, Clinical Studies, and Lessons Learned

Antibody–Drug Conjugates: Pharmacokinetic/Pharmacodynamic Modeling, Preclinical Characterization, Clinical Studies, and Lessons Learned

Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions

Development and Integration of Antibody–Drug Conjugate in Non-Hodgkin Lymphoma

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