CONTEXT: 
In the Phase 1 study CUDC-907-101, objective responses were reported in a number of patients with MYC-altered relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated with fimepinostat. The ongoing Phase 2 study CUDC-907-201 is designed to prospectively explore the efficacy of fimepinostat in this population.

OBJECTIVE: 
To evaluate the efficacy of fimepinostat as measured by objective response rate (ORR) in MYC-altered R/R DLBCL patients.

DESIGN: 
All R/R DLBCL patients enrolled from both studies are pooled here for a combined analysis by MYC status.

PATIENTS OR OTHER PARTICIPANTS: 
A total of 105 R/R DLBCL patients, 37 in CUDC-907-101 and 68 in CUDC-907-201, were included in the analysis. MYC-altered was defined as MYC expression ≥40% by immunohistochemical staining and/or MYC rearrangement or amplification by fluorescence in situ hybridization.

RESULTS: 
The median age at enrollment was 64 (20-93 years), 78 (74%) had de novo DLBCL, 85 (81%) had stage III or IV disease, and 97 (92%) had ECOG performance status of 0 or 1. The median number of previous treatments was 3 (2-10) and 23 (22%) patients had a previous stem cell transplant. Based on local and central testing, there were 60 MYC-altered, 22 non-MYC-altered, 23 MYC status unknown patients.

Overall, there were 19 total responses (9 complete responses [CR] and 10 partial responses [PR]). The ORR was 23.3% (14/60) in MYC-altered patients, which included 8 CR and 6 PR. Among the MYC-altered responders were 3 double-hit lymphoma (DHL) patients. The ORR was 13.6% (3/22) and 8.7% (2/23) in non-MYC-altered and MYC status unknown patients, respectively.

The median duration of response in MYC-altered patients was 13.7 months (range: 0.8 to 27.8+ months). Six MYC-altered responses were ongoing as of the data-cut. Two MYC-altered patients achieving CR discontinued treatment early to pursue stem cell transplantation.

CONCLUSIONS: 
Fimepinostat treatment has demonstrated durable clinical activity in primarily MYC-altered patients, including DHL. The biologic rationale, tolerable safety profile, and evidence of anti-tumor activity in MYC-altered RR DLBCL support the continued development of fimepinostat in this poor-prognosis patient population. Further analysis may also concentrate on screening characteristics most likely to predict the greatest benefit from fimepinostat treatment.

22 / Durable Responses Achieved in Patients with MYC-altered Relapsed/Refractory Diffuse Large B-cell Lymphoma Treated with Fimepinostat (CUDC-907): Combined Results from a Phase 1 and Phase 2 Study