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Landsburg DJ , Barta SK , Ramchandren R , Batlevi C , Iyer S , Kelly K , Micallef IN , Smith SM , Stevens DA , Alvarez M , Califano A , Shen Y , Bosker G , Parker J , Soikes R , Martinez E , von Roemeling R , Martell RE , Oki Y
Fimepinostat (CUDC-907) in patients with relapsed/refractory diffuse large B cell and high-grade B-cell lymphoma: report of a phase 2 trial and exploratory biomarker analyses
Br J Haematol. 2021 Oct;195(2) :201-209
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Abstract
Fimepinostat (CUDC-907), a first-in-class oral small-molecule inhibitor of histone deacetylase and phosphatidylinositol 3-kinase, demonstrated efficacy in a phase 1 study of patients with relapsed/refractory (R/R) diffuse large and high-grade B-cell lymphomas (DLBCL/HGBL), particularly those with increased MYC protein expression and/or MYC gene rearrangement/copy number gain (MYC-altered disease). Therefore, a phase 2 study of fimepinostat was conducted in this patient population with 66 eligible patients treated. The primary end-point of overall response (OR) rate for patients with MYC-IHC >/=40% (n = 46) was 15%. Subsequently, exploratory pooled analyses were performed including patients treated on both the phase 1 and 2 studies based upon the presence of MYC-altered disease as well as a biomarker identified by Virtual Inference of Protein activity by Enriched Regulon analysis (VIPER). For these patients with MYC-altered disease (n = 63), the overall response (OR) rate was 22% with seven responding patients remaining on treatment for approximately two years or longer, and VIPER yielded a three-protein biomarker classification with positive and negative predictive values of >/=85%. Prolonged durations of response were achieved by patients with MYC-altered R/R DLBCL/HGBL treated with single-agent fimepinostat. Combination therapies and/or biomarker-based patient selection strategies may lead to higher response rates in future clinical trials.
Notes
Landsburg, Daniel J Barta, Stefan K Ramchandren, Radhakrishnan Batlevi, Connie Iyer, Swaminathan Kelly, Kevin Micallef, Ivana N Smith, Sonali M Stevens, Don A Alvarez, Mariano Califano, Andrea Shen, Yao Bosker, Gideon Parker, Jefferson Soikes, Raul Martinez, Elizabeth von Roemeling, Reinhard Martell, Robert E Oki, Yasuhiro eng Curis, Inc England Br J Haematol. 2021 Oct;195(2):201-209. doi: 10.1111/bjh.17730. Epub 2021 Aug 2.