Initial Results of a Phase I Study of TNB-383B, a BCMA x CD3 Bispecific T-Cell Redirecting Antibody, in Relapsed/Refractory Multiple Myeloma

Rodriguez, Cesar; D’Souza, Anita; Shah, Nina; Voorhees, Peter M.; Buelow, Ben; Vij, Ravi; Kumar, Shaji

doi:10.1182/blood-2020-139893

Cited by 52 publications

(49 citation statements)

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“…In addition, the second-generation HLE-BiTE AMG 701 has achieved an 83% ORR in patients with R/R MM, the majority of responders experienced triple therapy failure [59]. Teclistamab [60], REGN5458 [61], CC-93269 [62] PF-06863135 [63], and TNB-383B [64] are other investigational T-cell engaging bsAbs designed to bind to BCMA with structural differences, all of them have entered the early clinical stage for treating patients with R/R MM with promising efficacy. The clinical advances of these newly developed BiTE antibodies and other T-cell engaging bsAbs are summarized in Table 3.…”

Section: Clinical Advances Of Bite In Hematological Malignanciesmentioning

confidence: 99%

The landscape of bispecific T cell engager in cancer treatment

et al. 2021

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T cell-based immunotherapies have revolutionized treatment paradigms in various cancers, however, limited response rates secondary to lack of significant T-cell infiltration in the tumor site remain a major problem. To address this limitation, strategies for redirecting T cells to treat cancer are being intensively investigated, while the bispecific T cell engager (BiTE) therapy constitutes one of the most promising therapeutic approaches. BiTE is a bispecific antibody construct with a unique function, simultaneously binding an antigen on tumor cells and a surface molecule on T cells to induce tumor lysis. BiTE therapy represented by blinatumomab has achieved impressive efficacy in the treatment of B cell malignancies. However, major mechanisms of resistance to BiTE therapy are associated with antigen loss and immunosuppressive factors such as the upregulation of immune checkpoints. Thus, modification of antibody constructs and searching for combination strategies designed to further enhance treatment efficacy as well as reduce toxicity has become an urgent issue, especially for solid tumors in which response to BiTE therapy is always poor. In particular, immunotherapies focusing on innate immunity have attracted increasing interest and have shown promising anti-tumor activity by engaging innate cells or innate-like cells, which can be used alone or complement current therapies. In this review, we depict the landscape of BiTE therapy, including clinical advances with potential response predictors, challenges of treatment toxicity and resistance, and developments of novel immune cell-based engager therapy.

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Section: Clinical Advances Of Bite In Hematological Malignanciesmentioning

confidence: 99%

The landscape of bispecific T cell engager in cancer treatment

et al. 2021

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“…Substitution of one Fab arm with one pair of identical nanobodies (Fab-VH2-Fc, Figure 1 d and Table 1 ) is the format of the trivalent bispecific IBI322 targeting CD47(Fab)/PD-L1(VH2) [ 141 ], for which clinical trials were very recently launched in the USA and China (NCT04338659, NCT04328831). TNB-383B is a similar anti-CD3(Fab)/BCMA(VH2) construct by TeneoBio based on the UniAbs platform, which has demonstrated very low CRS rate, solely grade 1–2 occurring in only 21% of the patients (n = 38) enrolled in a phase 1 trial [ 142 , 143 ].…”

Section: Bispecific Antibodiesmentioning

confidence: 99%

Principles and Current Clinical Landscape of Multispecific Antibodies against Cancer

Elshiaty

Schindler

Christopoulos

2021

IJMS

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Building upon the resounding therapeutic success of monoclonal antibodies, and supported by accelerating progress in engineering methods, the field of multispecific therapeutic antibodies is growing rapidly. Over 140 different molecules are currently in clinical testing, with excellent results in recent phase 1–3 clinical trials for several of them. Multivalent bispecific IgG-modified formats predominate today, with a clear tendency for more target antigens and further increased valency in newer constructs. The strategies to augment anticancer efficacy are currently equally divided between disruption of multiple surface antigens, and additional redirection of cytotoxic T or NK lymphocytes against the tumor. Both effects complement other modern modalities, such as tyrosine kinase inhibitors and adoptive cell therapies, with which multispecifics are increasingly applied in combination or merged, for example, in the form of antibody producing CAR-T cells and oncolytics. While mainly focused on B-cell malignancies early on, the contemporary multispecific antibody sector accommodates twice as many trials against solid compared to hematologic cancers. An exciting emerging prospect is the targeting of intracellular neoantigens using T-cell receptor (TCR) fusion proteins or TCR-mimic antibody fragments. Considering the fact that introduction of PD-(L)1 inhibitors only a few years ago has already facilitated 5-year survival rates of 30–50% for per se highly lethal neoplasms, such as metastatic melanoma and non-small-cell lung carcinoma, the upcoming enforcement of current treatments with “next-generation” immunotherapeutics, offers a justified hope for the cure of some advanced cancers in the near future.

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“…TNB-383B is a BCMA × CD3 bispecific T-cell redirecting antibody incorporating a unique anti-CD3 moiety that preferentially activates effector over regulatory T-cells and uncouples cytokine release from anti-tumor activity, as well as 2 heavy-chain-only anti-BCMA moieties for a 2:1 tumor associated antigen to CD3 stoichiometry. Preliminary results from the ongoing phase 1 dose escalation and expansion first-in-human study of TNB-383B are available (NCT03933735) [ 66 ]. RRMM have been exposed to at least 3 prior lines of therapy including a PI, an INIDs and an anti-CD38 monoclonal antibody.…”

Section: Bispecific Monoclonal Antibodies: Design and Mechanism Ofmentioning

confidence: 99%

Drug Conjugated and Bispecific Antibodies for Multiple Myeloma: Improving Immunotherapies off the Shelf

et al. 2021

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The impressive improvement of overall survival in multiple myeloma (MM) patients in the last years has been mostly related to the availability of new classes of drugs with different mechanisms of action, including proteasome inhibitors (PI), immunomodulating agents (IMiDs), and monoclonal antibodies. However, even with this increased potence of fire, MM still remains an incurable condition, due to clonal selection and evolution of neoplastic clone. This concept underlines the importance of immunotherapy as one of the most relevant tools to try to eradicate the disease. In line with this concept, active and passive immunotherapies represent the most attractive approach to this aim. Antibody-drug conjugate(s) (ADCs) and bispecific antibodies (BsAbs) include two innovative tools in order to limit neoplastic plasma cell growth or even, if used at the time of the best response, to potentially eradicate the tumoral clone. Following their promising results as single agent for advanced disease, at the recent 62nd ASH meeting, encouraging data of several combinations, particularly of ADC(s) with PI or IMiDs, have been reported, suggesting even better results for patients treated earlier. In this paper, we reviewed the characteristics, mechanism of action, and clinical data available for most relevant ADC(s) and BsAbs.

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Initial Results of a Phase I Study of TNB-383B, a BCMA x CD3 Bispecific T-Cell Redirecting Antibody, in Relapsed/Refractory Multiple Myeloma

Cited by 52 publications

References 0 publications

The landscape of bispecific T cell engager in cancer treatment

The landscape of bispecific T cell engager in cancer treatment

Principles and Current Clinical Landscape of Multispecific Antibodies against Cancer

Drug Conjugated and Bispecific Antibodies for Multiple Myeloma: Improving Immunotherapies off the Shelf

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