MOR202, a novel anti-CD38 monoclonal antibody, in patients with relapsed or refractory multiple myeloma: a first-in-human, multicentre, phase 1–2a trial

Raab, Marc S.; Engelhardt, Monika; Blank, Antje; Goldschmidt, Hartmut; Agis, Hermine; Blau, Igor Wolfgang; Einsele, Hermann; Ferstl, Barbara; Schub, Natalie; Röllig, Christoph; Weisel, Katja; Winderlich, Mark; Griese, Janine; Härtle, Stefan; Weirather, Johannes; Jarutat, Tiantom; Peschel, Christian; Chatterjee, Manik

doi:10.1016/s2352-3026(19)30249-2

Cited by 69 publications

(52 citation statements)

References 30 publications

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“…Clinically, it showed a lower frequency of IRRs compared to Dara iv. However, the ORR of MOR202 in combination with dexamethasone, lenalidomide or pomalidomide (28%, 65% or 43% respectively) was not higher than that of other anti-CD38 mAbs, despite the limitations of cross-trial comparisons [32].…”

Section: Naked Monoclonal Antibodiesmentioning

confidence: 83%

“…For example, differently from daratumumab, isatuximab mediates a direct cytotoxic effect against MM cells independently of the presence of Fc-cross-linking agents [69]. MOR202 does not induce CDC, decreasing the IRR rate at the cost of a reduced single-agent activity [32]. TAK-079 minimally binds to targets with a low density of CD38, leading to an enhanced depletion of high-density CD38+ target cells [95].…”

Section: Future Directions and Conclusionmentioning

confidence: 99%

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Monoclonal Antibodies to Treat Multiple Myeloma: A Dream Come True

D’Agostino

Innorcia

Boccadoro

et al. 2020

IJMS

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Immunotherapy is increasingly used in the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) are safe and effective ways to elicit immunotherapeutic responses. In 2015, daratumumab has become the first mAb approved by the Food and Drug Administration for clinical use in MM and, in the last 5 years, a lot of clinical and preclinical research has been done to optimize the use of this drug class. Currently, mAbs have already become part of standard-of-care combinations for the treatment of relapsed/refractory MM and very soon they will also be used in the frontline setting. The success of simple mAbs (‘naked mAbs’) prompted the development of new types of molecules. Antibody–drug conjugates (ADCs) are tumor-targeting mAbs that release a cytotoxic payload into the tumor cells upon antigen binding in order to destroy them. Bispecific antibodies (BiAbs) are mAbs simultaneously targeting a tumor-associated antigen and an immune cell-associated antigen in order to redirect the immune cell cytotoxicity against the tumor cell. These different constructs produced solid preclinical data and promising clinical data in phase I/II trials. The aim of this review article is to summarize all the recent developments in the field, including data on naked mAbs, ADCs and BiAbs.

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Section: Naked Monoclonal Antibodiesmentioning

confidence: 83%

Section: Future Directions and Conclusionmentioning

confidence: 99%

Monoclonal Antibodies to Treat Multiple Myeloma: A Dream Come True

D’Agostino

Innorcia

Boccadoro

et al. 2020

IJMS

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“…MOR202 is a fully human anti-CD38 antibody that is currently under investigation in phase I/IIa clinical trials in MM. The ability of MOR202 of inducing both ADCC and ADCP effects in MM cells makes this molecule a promising candidate for new therapeutic regimens in the management of patients with MM [47]. As for the other anti-CD38 moAbs, the cytotoxic effect of MOR202 on MM cells is augmented by IMiD compounds, such as lenalidomide and pomalidomide.…”

Section: Evidence Supporting Cd38 As An Ideal Target For Treating Al mentioning

confidence: 99%

CD38 and Anti-CD38 Monoclonal Antibodies in AL Amyloidosis: Targeting Plasma Cells and beyond

Roccatello

Fenoglio

Sciascia

et al. 2020

IJMS

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Immunoglobulin light chain amyloidosis (AL amyloidosis) is a rare systemic disease characterized by monoclonal light chains (LCs) depositing in tissue as insoluble fibrils, causing irreversible tissue damage. The mechanisms involved in aggregation and deposition of LCs are not fully understood, but CD138/38 plasma cells (PCs) are undoubtedly involved in monoclonal LC production.CD38 is a pleiotropic molecule detectable on the surface of PCs and maintained during the neoplastic transformation in multiple myeloma (MM). CD38 is expressed on T, B and NK cell populations as well, though at a lower cell surface density. CD38 is an ideal target in the management of PC dyscrasia, including AL amyloidosis, and indeed anti-CD38 monoclonal antibodies (MoAbs) have promising therapeutic potential. Anti-CD38 MoAbs act both as PC-depleting agents and as modulators of the balance of the immune cells. These aspects, together with their interaction with Fc receptors (FcRs) and neonatal FcRs, are specifically addressed in this paper. Moreover, the initiallyavailable experiences with the anti-CD38 MoAb DARA in AL amyloidosis are reviewed.

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“…MOR202 (MOR03087, TJ202) is a fully humanized IgG1λ mAb that exhibited an objective response rate (ORR) of 29% in a phase II trial with dexamethasone in patients who had previously received four lines of therapy [28]. In addition, this drug has shown some promising efficacy when combined with immunomodulators [29,30]. MOR202 also appears to offer the advantage of requiring reduced infusion times and is associated with reduced infusion-related reactions compared to daratumumab or isatuximab, possibly due to its lack of dependency on CDC as a function of its activity.…”

Section: Mabs Targeting Cd38mentioning

confidence: 99%

Emerging Monoclonal Antibodies for the Treatment of Multiple Myeloma

Abramson¹

2021

Monoclonal Antibodies

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Therapeutic measures designed to treat multiple myeloma (MM) have undergone a fundamental shift over the past two decades as a number of small molecules that attack this cancer by different mechanisms, including proteasome blockade, immunomodulation, and histone deacetylase (HDAC) inhibition, have been introduced. The insertion of monoclonal antibodies (mAbs) into the mix began in 2015 with the U.S. Food and Drug Administration (FDA) approval of daratumumab and elotuzumab, which target CD38 and SLAMF7, respectively. In 2020, they were joined by another anti-CD38 mAb, isatuximab, and the bispecific antibody-drug conjugate (ADC) belantamab mafodotin, which targets the B-cell maturation antigen (BCMA). This review focuses on additional mAbs currently under clinical study for MM. These include several BCMAxCD3-directed bispecifics (AMG 420, AMG 701, REGN5458, REGN5459, teclistamab, and TNB-383B), the ADCs indatuximab ravtansine and STRO-001, and checkpoint inhibitors, although the future status of the latter is in a state of flux due to toxicity issues that arose in trials in which these drugs, especially PD-1 or PD-L1 blockers, were combined with immunomodulators.

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MOR202, a novel anti-CD38 monoclonal antibody, in patients with relapsed or refractory multiple myeloma: a first-in-human, multicentre, phase 1–2a trial

Cited by 69 publications

References 30 publications

Monoclonal Antibodies to Treat Multiple Myeloma: A Dream Come True

Monoclonal Antibodies to Treat Multiple Myeloma: A Dream Come True

CD38 and Anti-CD38 Monoclonal Antibodies in AL Amyloidosis: Targeting Plasma Cells and beyond

Emerging Monoclonal Antibodies for the Treatment of Multiple Myeloma

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