Contributions
Abstract: EP944
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Despite newly emerging therapies, significant unmet need remains in Multiple Myeloma (MM). Patients require multiple lines of therapy and ultimately succumb to disease. Therapies that are active, but well tolerated are crucial for these patients. Therapeutic antibodies have transformed the MM treatment paradigm, allowing patients to achieve deeper responses with minimal added toxicity, particularly in the therapeutic combination setting. SEA-BCMA is an investigational humanized nonfucosylated IgG1 antibody targeting BCMA, which shows preclinical evidence of encouraging activity and tolerability1. Preclinical studies show SEA-BCMA elicits anti-tumor activity through three mechanisms of action: (1) increased binding to FcγRIII through SEA technology leading to enhanced antibody dependent cellular cytotoxicity; (2) engagement of antibody dependent cellular phagocytosis; (3) blockade of the proliferative signals from BCMA ligand binding.
Aims
Here we show the preclinical combination of SEA-BCMA with therapeutics relevant to MM and BCMA targeting
Methods
We tested in vitro and in vivo combinations of SEA-BCMA with daratumumab, IMiDs, ADCs, and gammasecretase inhibitors.
Results
SEA-BCMA combines effectively with daratumumab in preclinical MM tumor xenograft models, creating an opportunity for a well-tolerated, antibody-based combination regimen. We also show increased anti-MM activity when SEA-BCMA is combined with standard of care IMiDs. In addition, SEA-BCMA combines effectively with antibody-drug conjugates in preclinical MM tumor xenografts leading to improved anti-tumor activity and prolonged survival in mice. Lastly, we evaluated SEA-BCMA in combination with gamma secretase inhibitors (GSIs), which block membrane cleavage of BCMA leading to increased membrane BCMA and decreased soluble BCMA 2. We show here that GSI treatment enhances the SEA-BCMA activity by increasing Fcγ receptor activation and subsequent effector function.
Conclusion
In summary, SEA-BCMA shows preclinical evidence of combinability with multiple agents. SEA-BCMA is currently enrolling in a Phase 1 clinical trial for relapsed / refractory multiple myeloma (NCT03582033), and ongoing preclinical work supports potential combination strategies for future clinical investigation.
1) Van Epps et al., Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl): Abstract nr 3833
2) Laurent et al. Nat Commun 6, 7333 (2015). https://doi.org/10.1038/ncomms8333
Keyword(s): Antibody, Myeloma
Abstract: EP944
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Despite newly emerging therapies, significant unmet need remains in Multiple Myeloma (MM). Patients require multiple lines of therapy and ultimately succumb to disease. Therapies that are active, but well tolerated are crucial for these patients. Therapeutic antibodies have transformed the MM treatment paradigm, allowing patients to achieve deeper responses with minimal added toxicity, particularly in the therapeutic combination setting. SEA-BCMA is an investigational humanized nonfucosylated IgG1 antibody targeting BCMA, which shows preclinical evidence of encouraging activity and tolerability1. Preclinical studies show SEA-BCMA elicits anti-tumor activity through three mechanisms of action: (1) increased binding to FcγRIII through SEA technology leading to enhanced antibody dependent cellular cytotoxicity; (2) engagement of antibody dependent cellular phagocytosis; (3) blockade of the proliferative signals from BCMA ligand binding.
Aims
Here we show the preclinical combination of SEA-BCMA with therapeutics relevant to MM and BCMA targeting
Methods
We tested in vitro and in vivo combinations of SEA-BCMA with daratumumab, IMiDs, ADCs, and gammasecretase inhibitors.
Results
SEA-BCMA combines effectively with daratumumab in preclinical MM tumor xenograft models, creating an opportunity for a well-tolerated, antibody-based combination regimen. We also show increased anti-MM activity when SEA-BCMA is combined with standard of care IMiDs. In addition, SEA-BCMA combines effectively with antibody-drug conjugates in preclinical MM tumor xenografts leading to improved anti-tumor activity and prolonged survival in mice. Lastly, we evaluated SEA-BCMA in combination with gamma secretase inhibitors (GSIs), which block membrane cleavage of BCMA leading to increased membrane BCMA and decreased soluble BCMA 2. We show here that GSI treatment enhances the SEA-BCMA activity by increasing Fcγ receptor activation and subsequent effector function.
Conclusion
In summary, SEA-BCMA shows preclinical evidence of combinability with multiple agents. SEA-BCMA is currently enrolling in a Phase 1 clinical trial for relapsed / refractory multiple myeloma (NCT03582033), and ongoing preclinical work supports potential combination strategies for future clinical investigation.
1) Van Epps et al., Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl): Abstract nr 3833
2) Laurent et al. Nat Commun 6, 7333 (2015). https://doi.org/10.1038/ncomms8333
Keyword(s): Antibody, Myeloma