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ASH 2024 | Genome-wide CRISPR/Cas9 knockout screen to determine novel rocbrutinib combinations for CLL
In this video, Jennifer Woyach, MD, The Ohio State University, Columbus, OH, briefly comments on the findings of a genome-wide CRISPR/Cas9 knockout screen that aimed to reveal which classes of agents could potentially be combined with the fourth-generation BTK inhibitor (BTKi) rocbrutinib (LP-168) for treating chronic lymphocytic leukemia (CLL). This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (AI-generated)
Rocbrutinib, or LP-168, is a novel, fourth-generation covalent and non-covalent inhibitor of BTK, that’s extremely selective. As we know, the field of CLL is moving towards fixed-duration or MRD-guided treatments, which would be intermittent rather than putting people onto a BTK inhibitor continuously. So we were really interested with rocbrutinib, whether we could find good combination partners for that drug...
Rocbrutinib, or LP-168, is a novel, fourth-generation covalent and non-covalent inhibitor of BTK, that’s extremely selective. As we know, the field of CLL is moving towards fixed-duration or MRD-guided treatments, which would be intermittent rather than putting people onto a BTK inhibitor continuously. So we were really interested with rocbrutinib, whether we could find good combination partners for that drug. We know that BCL2 is a good combination partner in general for BTK inhibitors. But for this purpose, we undertook a genome-wide CRISPR-Cas9 screen, where we were looking for synthetic lethality with rocbrutinib. One of the hits that came up was BCL2. And so we have investigated preclinically combinations of rocbrutinib with BCL2 inhibitors, a few different ones, which all are showing very exciting preclinical efficacy. We’re really excited to use these data to hopefully move into clinical trials of rocbrutinib with BCL2 inhibitors.
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Disclosures
AstraZeneca: Consultancy; Newave: Consultancy; Genentech, Inc.: Consultancy; Janssen: Research Funding; Loxo Lilly: Consultancy; BeiGene: Consultancy; AbbVie: Research Funding; Merck: Consultancy; Pharmacyclics: Consultancy, Research Funding; Schrodinger: Research Funding; Morphosys: Research Funding.
