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DRUG:

pacanalotamab (AMG 420)

i
Other names: AMG 420, BI 836909
Associations
Trials
Company:
Amgen, Boehringer Ingelheim
Drug class:
CD3 agonist, BCMA inhibitor
Related drugs:
Associations
Trials
11ms
Assessment of AMG 420 in Subjects With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov)
P1, N=23, Terminated, Amgen | Phase classification: P1b --> P1 | Completed --> Terminated; Amgen re-evaluated the portfolio and decided to discontinue clinical development activities for AMG 420.
Phase classification • Trial termination
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pacanalotamab (AMG 420)
over1year
INFECTIONS FOLLOWING BISPECIFIC ANTIBODIES IN MYELOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2023)
Despite promising efficacy in MM, BsAbs may come with substantial infection risk, warranting more detailed analysis of infections and immune phenotyping to guide targeted supportive care. Table – Summary of included studiesAgent Target Source Phase Enrolment (mm/yy) N Median prior lines All- Grade Infection N (%) Grade ≥3 Infection N (%) Alnuctamab (CC-93269) BCMA Wong 2022 I 03/18- 68 4 23 (34) 6 (9) ABBV-383 BCMA Voorhees 2022 I 10/22- 174 5 61/124 (50) 39/124 (22) Elranatamab BCMA Raje 2022 I 10/21- 123 5 82 (67) 43 (35) Linvoseltamab (REGN545) BCMA Bumma 2022 Ib/II 1/19- 252 5 136 (54) 73 (29) Pacanalotamab (AMG-420) BCMA Topp 2020 I 3/19 – 4/22 42 5 14 (33) 10 (24) Teclistamab BCMA Moreau 2022 I/II 09/20- 165 5 126 (77) 57 (45) Teclistamab + daratumumab BCMA + CD38 Rodriguez- Otero 2022 II 03/21- 46 5 29 (63) 8 (17) Forimtamig (RG6234) GPRC5D Carlo- Stella 2022 I 11/20- IV: 51 SC: 57 IV: 5 SC: 4 IV: 31 (61) SC: 26 (46) IV:11 (22) SC:15 (27) Talquetamab GPRC5D Chari 2022 I/II 02/21- 288 5 153 (53) 46 (16) Talquetamab + daratumumab GPRC5D + CD38 Van de Donk 2022 II 09/21- 46 5 23 (50) 6 (13) Cevostamab (BFCR4350A) FcRH5 Trudel 2021 I 07/21- 161 6 68 (43) 18 (11) Bispecific, Multiple myeloma, Cellular therapy
Retrospective data • Review
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Darzalex (daratumumab) • Elrexfio (elranatamab-bcmm) • Talvey (talquetamab-tgvs) • Tecvayli (teclistamab-cqyv) • alnuctamab (CC-93269) • ABBV-383 IV • cevostamab (RG6160) • forimtamig (RG6234) • linvoseltamab (REGN5458) • pacanalotamab (AMG 420)
over2years
Leveraging a physiologically-based quantitative translational modeling platform for designing B cell maturation antigen-targeting bispecific T cell engagers for treatment of multiple myeloma. (PubMed, PLoS Comput Biol)
The biodistribution of TCEs was verified by positron emission tomography imaging of [89Zr]AMG211 (a carcinoembryonic antigen-targeting TCE) in patients. The final model simulations indicated that the number of immune synapses is similar (~55/tumor cell) between two distinct clinical stage B cell maturation antigen (BCMA)-targeting TCEs, PF-06863135 in an IgG format and AMG420 in a BiTE format, at their respective efficacious doses in multiple myeloma patients. This result demonstrates the applicability of the developed computational modeling framework to molecular design optimization and clinical benchmarking for TCEs, thus suggesting that this framework can be applied to other targets to provide a quantitative means to facilitate model-informed best-in-class TCE discovery and development.
Journal • IO biomarker
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CEACAM5 (CEA Cell Adhesion Molecule 5)
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Elrexfio (elranatamab-bcmm) • AMG 211 • pacanalotamab (AMG 420)
almost4years
T-cell redirecting bispecific antibodies targeting BCMA for the treatment of multiple myeloma. (PubMed, Oncotarget)
Several phase 1, dose-escalation studies show pronounced activity of BCMA-targeting bispecific antibodies, including teclistamab, AMG420 and CC-93269, in heavily pretreated MM patients. Cytokine release syndrome is the most common adverse event, which can be adequately managed with tocilizumab or steroids...GPRC5D, CD38 and FcRH5), are also evaluated in early phase clinical trials. Such bispecific antibodies, targeting other antigens, may be given to patients with low baseline BCMA expression, disease with substantial heterogeneity in BCMA expression, following prior BCMA-targeted therapy, or combined with BCMA bispecific antibodies to prevent development of antigen escape.
Journal
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CD38 (CD38 Molecule)
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Actemra IV (tocilizumab) • Tecvayli (teclistamab-cqyv) • alnuctamab (CC-93269) • pacanalotamab (AMG 420)
4years
[VIRTUAL] Local Activator and T Cell Engager (αBCMA x αPD-L1 x αCD3) with Enhanced Tumor Killing and Minimal Cytokine Release for the Treatment of Multiple Myeloma (ASH 2020)
The most advanced of these is AMG 420, which showed significantly improved response rates in relapsed/refractory multiple myeloma (MM) patients...Collectively, these findings demonstrate that the simultaneous T cell redirection and tumor-specific checkpoint inhibition with the LocATE leads to an improved therapeutic index with robust tumor cell killing and low levels of cytokine release. Capable of counteracting adaptive immune resistance caused by increased PD-1/PD-L1 signaling, the LocATE antibody has the prospect to significantly improve survival for multiple myeloma patients.
PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • LAG3 (Lymphocyte Activating 3) • TNFA (Tumor Necrosis Factor-Alpha) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IL2RA (Interleukin 2 receptor, alpha) • IL2 (Interleukin 2)
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PD-L1 expression • PD-1 expression • LAG3 expression
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pacanalotamab (AMG 420)
over4years
B-Cell Maturation Antigen (BCMA) as a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma. (PubMed, Int J Mol Sci)
Immunotherapeutic agents have been at the forefront of research designed to block BCMA activity. These agents encompass monoclonal antibodies, such as the drug conjugate belantamab mafodotin; bispecific T-cell engager strategies exemplified by AMG 420; and chimeric antigen receptor (CAR) T-cell therapeutics that include idecabtagene vicleucel (bb2121) and JNJ-68284528.
Review • Journal
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CD38 (CD38 Molecule)
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Blenrep (belantamab mafodotin-blmf) • Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel) • pacanalotamab (AMG 420)
almost5years
Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma. (PubMed, Cancers (Basel))
Two mAbs have been approved for the treatment of MM: the anti-CD38 daratumumab for newly-diagnosed and relapsed/refractory patients and the anti-CS1 elotuzumab in the relapse setting. Encouraging results have been reported with antibody drug conjugates (e.g., GSK2857916) and bispecific T cell engagers (BiTEs), including AMG420, which re-directs T cell-mediated cytotoxicity against MM cells. Here, we present an overview on mAbs currently approved for the treatment of MM and promising compounds under investigation.
Review • Journal
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PD-1 (Programmed cell death 1)
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Darzalex (daratumumab) • Empliciti (elotuzumab) • Blenrep (belantamab mafodotin-blmf) • pacanalotamab (AMG 420)