CUDC-907 in relapsed/refractory diffuse large B-cell lymphoma, including patients with MYC-alterations: results from an expanded phase I trial

Yasuhiro Oki, Kevin R Kelly, Ian Flinn, Manish R Patel, Robert Gharavi, Anna Ma, Jefferson Parker, Amir Hafeez, David Tuck, Anas Younes, Yasuhiro Oki, Kevin R Kelly, Ian Flinn, Manish R Patel, Robert Gharavi, Anna Ma, Jefferson Parker, Amir Hafeez, David Tuck, Anas Younes

Abstract

CUDC-907 is a first-in-class, oral small molecule inhibitor of both HDAC (class I and II) and PI3K (class Iα, β, and δ) enzymes, with demonstrated anti-tumor activity in multiple pre-clinical models, including MYC-driven ones. In this report, we present the safety and preliminary activity results of CUDC-907, with and without rituximab, in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), with a particular focus on those with MYC-altered disease. Thirty-seven DLBCL patients were enrolled, 14 with confirmed MYC-altered disease. Twenty-five patients received monotherapy treatment, and 12 received the combination of CUDC-907 with rituximab. CUDC-907 monotherapy and combination demonstrated similar safety profiles consisting primarily of Grade 1/2 hematologic and gastrointestinal events. The most frequently reported Grade ≥3 treatment-related events were thrombocytopenia, neutropenia, diarrhea, fatigue, and anemia. Eleven responses (5 complete responses and 6 partial responses) were reported, for a response rate of 37% (11 out of 30) in evaluable patients [30% (11 out of 37) including all patients]. The objective response rate in evaluable MYC-altered DLBCL patients was 64% (7 out of 11; 4 complete responses and 3 partial responses), while it was 29% (2 out of 7) in MYC unaltered, and 17% (2 out of 12) in those with unknown MYC status. Median duration of response was 11.2 months overall; 13.6 months in MYC-altered patients, 6.0 months in MYC unaltered, and 7.8 months in those with MYC status unknown. The tolerable safety profile and encouraging evidence of durable anti-tumor activity, particularly in MYC-altered patients, support the continued development of CUDC-907 in these populations of high unmet need. (clinicaltrials.gov identifier: 01742988).

Trial registration: ClinicalTrials.gov NCT01742988.

Copyright© Ferrata Storti Foundation.

Figures

Figure 1.
Figure 1.
Extended progression-free survival (PFS) in MYC-altered patients. Kaplan-Meier PFS curve for all patients (n=37) on the trial (solid black line) along with subsets based on MYC status. MYC-altered patients (n=14, blue dotted line), MYC negative patients (n=8, red dashed line) and MYC unknown (n=15, green dash-dotted line). Median PFS was 2.9 months for all diffuse large B-cell lymphoma (DLBCL) patients and 21.8 months for the MYC-altered patients, respectively. x-axis in months; y-axis is the proportion of patients.
Figure 2.
Figure 2.
Extended duration of response in MYC-altered patients. Kaplan-Meier duration of response curve for all responding patients (n=11) on the trial (solid black line) along with subsets based on MYC status. MYC-altered patients (n=7, blue dotted line), MYC negative patients (n=2, red dashed line) and MYC unknown (n= 2, green dash-dotted line). x-axis in months; y-axis is the proportion of patients.

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