ArticleCancer research communications2024
Preclinical Evaluation of STI-8811, a Novel Antibody-Drug Conjugate Targeting BCMA for the Treatment of Multiple Myeloma.
Article in Cancer research communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Antibody-Drug Conjugates in Hematological Malignancies: Current Landscape and Future Perspectives.International journal of molecular sciences · 2026Review
- Structure-based prediction reveals a difference in the binding mode of anti-BCMA antibodies to BCMA and soluble BCMA.Leukemia · 2026Article
Corrections and comments
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment for patients with multiple myeloma has experienced rapid development and improvement in recent years; however, patients continue to experience relapse, and multiple myeloma remains largely incurable. B-cell maturation antigen (BCMA) has been widely recognized as a promising target for treatment of multiple myeloma due to its exclusive expression in B-cell linage cells and its critical role in the growth and survival of malignant plasma cells. Here, we introduce STI-8811, a BCMA-targeting antibody-drug conjugate (ADC) linked to an auristatin-derived duostatin payload via an enzymatically cleavable peptide linker, using our proprietary C-lock technology. STI-8811 exhibits target-specific binding activity and rapid internalization, leading to G2/M cell-cycle arrest, caspase 3/7 activation, and apoptosis in BCMA-expressing tumor cells in vitro. Soluble BCMA (sBCMA) is shed by multiple myeloma cells into the blood and increases with disease progression, competing for ADC binding and reducing its efficacy. We report enhanced cytotoxic activity in the presence of high levels of sBCMA compared with a belantamab mafodotin biosimilar (J6M0-mcMMAF). STI-8811 demonstrated greater in vivo activity than J6M0-mcMMAF in solid and disseminated multiple myeloma models, including tumor models with low BCMA expression and/or in large solid tumors representing soft-tissue plasmacytomas. In cynomolgus monkeys, STI-8811 was well tolerated, with toxicities consistent with other BCMA-targeting ADCs with auristatin payloads in clinical studies. STI-8811 has the potential to outperform current clinical candidates with lower toxicity and higher activity under conditions found in patients with advanced disease. Significance: STI-8811 is a BCMA-targeting ADC carrying a potent auristatin derivative. We report unique binding properties which maintain potent cytotoxic activity under sBCMA-high conditions that hinder the clinical efficacy of current BCMA-targeting ADC candidates. Beyond disseminated models of multiple myeloma, we observed efficacy in solid tumor models of plasmacytomas with low and heterogenous BCMA expressions at a magnitude and duration of response exceeding that of clinical comparators.
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