Curis, Inc., recently presented promising results from the Phase 1 study of its drug candidate CUDC-907a in severely pre-treated patients with relapsed/refractory diffuse large B cell lymphoma (RR-DLBCL). The results, from the ongoing trial’s finished dose escalation stage, revealed several complete and partial responses to CUDC-907 treatment, including in patients with alterations of the MYC oncogene, a RR-DLBCL subgroup for which no approved treatments exist. Planning for a larger Phase 2 trial is underway.
The data were presented at the recent annual meeting of the American Society of Hematology (ASH) in Orlando.
The trial enrolled 25 patients with relapsed/refractory diffuse large B cell lymphoma (RR-DLBCL) for treatment either with CUDC-907 as a monotherapy or with CUDC-907 in combination with the standard dose of rituximab. Of these, 18 total patients could be evaluated for responses, and eight objective responses were reported: two complete responses (CRs) and five partial responses (PRs) in the monotherapy group, and one CR in the combination therapy group. Results from a retrospective post hoc analysis further revealed that five of these eight patients had tumors with alteration in the MYC oncogene, while among the three remaining, two had MYC protein expression in fewer than 40% of their tumor cells.
The most commonly occurring drug-related side effects included diarrhea, fatigue, and nausea.
Preclinical trials results showed that CUDC-907 treatment on DLBCL cell lines led to a complete suppression of MYC protein levels, and in multiple in vivo MYC-altered DLBCL models, CUDC-907 treatment resulted in observed anti-tumor activity. “Preliminary data for CUDC-907 in patients with multiply relapsed DLBCL appear encouraging, even in those with MYC-altered lymphoma, providing the rationale for further investigation in a Phase 2 trial,” Dr. Anas Younes, MD, chief of the Lymphoma Service of the Memorial Sloan Kettering Cancer Center and the trial’s principal investigator, said in a press release. “There is a high unmet need for novel therapies for patients with RR-DLBCL, and particularly for the subset of patients with MYC-altered DLBCL due to their poor prognosis.”
The company now is planning a Phase 2 clinical trial to evaluate CUDC-907 in 120 patients with MYC-altered relapsed/refractory DLBCL. These patients will again be randomized to receive either CUDC-907 alone or in combination with a rituximab standard dose until disease progression, or treatment discontinuation for safety or other reasons. The trial’s primary outcome is the rate of objective response, while secondary outcomes include the determination of progression free survival, overall survival, and the duration of response. Final dose results from Phase 1 recommend a five-day treatment of CUDC-907 at 60 mg, followed by two days of no treatment for this new study.
If the Phase 2 data show promise, patient enrollment will be expanded and Curis will open discussions with the U.S. Food and Drug Admistration regarding a potential registration plan.
“We are pleased to report promising clinical activity of CUDC-907 in patients with DLBCL, particularly those with tumors that harbor MYC alterations,” said Ali Fattaey, PhD, Curis’ president and chief executive officer. “These clinical results are consistent with our preclinical observations where CUDC-907 has a rapid and dramatic effect on MYC protein levels and provides significant anti-tumor activity in in vivo models. We are thankful to our patients for their participation in the Phase 1 clinical trial and, based on these data, we expect the start of a Phase 2 trial that will exclusively enroll patients with relapsed/ refractory DLBCL known to have MYC alterations based on pre-specified selection criteria.”
Curis is a biotechnology company focused on the development and commercialization of innovative cancer drug candidates. Its lead development candidate, CUDC-907, is a dual HDAC and PI3K inhibitor being investigated in patients with lymphomas and solid tumors.