On June 14, 2019 Xynomic Pharmaceuticals Holdings, Inc. ("Xynomic", Nasdaq: XYN), a clinical stage US-China oncology drug development company, reported that Xynomic has dosed the first patient in a Phase 1/2 trial that combines abexinostat with ibrutinib in patients with relapsed/refractory mantle cell lymphoma ("r/r MCL") or relapsed/refractory diffuse large B-cell lymphoma ("r/r DLBCL") at Memorial Sloan Kettering Cancer Center (MSK) (Press release, Xynomic Pharmaceuticals, JUN 14, 2019, View Source [SID1234537078]). This trial will enroll approximately 40 patients to assess the safety and efficacy of the combination in patients with r/r MCL or r/r DLBCL. This trial will also explore the biologic predictors of response and resistance to dual B-cell receptor (BCR) and histone deacetylase (HDAC) inhibition. Janssen Biotech, Inc. is providing ibrutinib as part of the study, with Xynomic providing abexinostat and funding support for the trial being conducted at MSK.
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Mantle cell lymphoma (MCL) has an annual incidence of approximately 6,500 in G7 countries, according to DR/Decision Resources, LLC. Ibrutinib has been approved by the United States Food and Drug Administration (FDA) for relapsed MCL and has response rates of 60-70% and median duration of response of 18 months. Abexinostat as a mono therapy has been shown to have response rate of 15.4% (7.7% complete response and 7.7% partial response) in r/r MCL patients. Researchers at MSK are testing whether abexinostat/ibrutinib combo could potentially improve response rates and duration of responses in r/r MCL patients, subject to the assessment upon the completion of the trial.
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin’s lymphoma (NHL) subtype according to the Leukemia & Lymphoma Society (LLS). Researchers at MSK have shown preclinical data demonstrating that dual targeting of Bruton’s tyrosine kinase (BTK) in the BCR pathway with ibrutinib and inhibition of MyD88-driven NF-kB activation with a HDAC inhibitor lead to synergistic anti-lymphoma activity in MyD88 mutated, ABC-subtype DLBCL both in vitro and in vivo.
Abexinostat is a novel HDAC inhibitor in global pivotal trials against NHL and renal cell carcinoma. Ibrutinib is a first-in-class BTK inhibitor jointly developed and commercialized as IMBRUVICA by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company and has been approved for multiple hematological malignances and chronic graft-versus-host-disease (cGVHD).