Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Lymphoma: Chemotherapy, excluding Pre-Clinical Models: NHL – New Drugs
Sixty-three heavily pre-treated pts with lymphoma or multiple myeloma have received CUDC-907 in 21-day cycles according to once daily (QD), intermittent (BIW or TIW), or five days on/two days off (5/2) dosing schedules. CUDC-907 was escalated in 30 mg increments such that pts received 30-60 mg QD, 60-150 mg intermittently, or 60 mg 5/2. A dose expansion using the 60 mg 5/2 dose and schedule is ongoing. Thus far, CUDC-907 has demonstrated a manageable side effect profile and sustained clinical efficacy, particularly in the subset of pts with RR DLBCL.
The most common treatment-related adverse events (AEs) were diarrhea (54%; 5% Grade ≥3), fatigue (37%; 3% Grade ≥3), nausea (22%) and thrombocytopenia (18%; 14% Grade ≥3), with dose limiting toxicities of hyperglycemia (QD and BIW schedules) and diarrhea (QD and TIW schedules). Side effects were reversible and manageable. Among 11/18 subjects with RR DLBCL who were evaluable for disease response, 6/11 (55%) achieved objective responses (2 CRs and 4 PRs); lasting a median of 119 days (range: 48 - 354+). Of 7 pts with sufficient tissue, 3 response-evaluable pts were found to over-express MYC and BCL2 by IHC, meeting criteria applied to “double-expressor” (DE) DLBCL. On CUDC-907 monotherapy, 2/3 confirmed pts with DE DLBCL have attained objective responses: 1 ongoing CR (followed by autologous stem cell transplant) and 1PR (lasting 132 days). The third response-evaluable pt with DE DLBCL has experienced lengthy stabilization of disease (171+ days).
Signals emerging from preclinical and clinical studies suggest that pts with DLBCL, including those with particularly aggressive disease, may derive benefit from treatment with CUDC-907. Enrollment of pts with RR DLBCL is ongoing into the expansion phase of the Phase 1 trial that is testing CUDC-907 on the 60 mg 5/2 RP2D as monotherapy and in combination with rituximab. Tissue obtained from pts with RR DLBCL treated with CUDC-907 will be assessed for MYC, BCL2, and other genetic aberrations that will be correlated with clinical outcomes observed in the trial. A Phase 2 trial of CUDC-907 in RR NHL is currently being planned, with emphasis on MYC aberrations.
Disclosures: Younes: Celgene: Honoraria ; Incyte: Honoraria ; Janssen: Honoraria ; Seattle Genetics: Honoraria , Research Funding ; Bayer: Honoraria ; Bristol Meyer Squibb: Honoraria ; Novartis: Research Funding ; Sanofi-Aventis: Honoraria ; Johnson and Johnson: Research Funding ; Curis: Research Funding ; Takeda Millenium: Honoraria . Berdeja: Celgene: Research Funding ; Onyx: Research Funding ; MEI: Research Funding ; BMS: Research Funding ; Takeda: Research Funding ; Janssen: Research Funding ; Array: Research Funding ; Acetylon: Research Funding ; Curis: Research Funding ; Abbvie: Research Funding ; Novartis: Research Funding . Flinn: Celgene Corporation: Research Funding . Clancy: Curis: Employment , Equity Ownership . Ma: Curis: Employment , Equity Ownership . Sun: Curis: Employment , Equity Ownership . Tian: Curis: Employment , Equity Ownership . Wang: Curis: Employment , Equity Ownership . Viner: Curis: Employment , Equity Ownership .
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*signifies non-member of ASH