Curis, Inc. (NASDAQ:CRIS), a biotechnology company focused on the development and commercialization of innovative drug candidates for the treatment of human cancers, announced results from the completed dose escalation and ongoing expansion stages of a Phase 1 trial of CUDC-907, an oral dual inhibitor of histone deacetylase (HDAC) and phosphoinositide 3-kinase (PI3K) enzymes. Data were presented at the Annual Meeting of American Society of Clinical Oncology (ASCO) that is being held in Chicago, IL. At the recommended Phase 2 dose and schedule, CUDC-907 has demonstrated evidence of clinical activity with objective responses observed in patients with relapsed/ refractory diffuse large B cell lymphoma (DLBCL) and Hodgkin’s lymphoma (HL). Two complete responses (CRs) and 4 partial responses (PRs) were reported in 10 response evaluable patients with DLBCL, including 3 responses (1 CR and 2 PRs) in patients with transformed follicular lymphoma (t-FL/DLBCL), a very difficult to treat subset of DLBCL. One patient with HL experienced partial response out of a total of 12 response evaluable patients with HL. In addition, stable disease (SD) has been observed in 25 of 44 response evaluable patients across various lymphomas and multiple myeloma (MM).
“Despite a number of investigational agents being tested in patients with DLBCL, this disease continues to be an area of significant unmet need, especially in the relapsed/ refractory setting,” said Dr. Anas Younes, MD, Chief of the Lymphoma Service of the Memorial Sloan Kettering Cancer Center in New York City and the Principal Investigator of the study. “The single agent activity of CUDC-907, especially in patients with relapsed/ refractory DLBCL is promising and supports its further investigation in this disease.”
“We are pleased to have determined a safe and tolerable dose and schedule for the administration of CUDC-907 and are encouraged to see objective responses in patients with advanced, relapsed/ refractory DLBCL,” said Ali Fattaey, Ph.D., Curis’ President and Chief Executive Officer. “After completing the expansion arms of the ongoing trial in patients with relapsed/ refractory DLBCL treated with CUDC-907 either as monotherapy or in combination with rituximab, we expect to initiate a registration directed Phase 2 study in this patient population later this year.”
The Phase 1 dose escalation and expansion study was designed to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose, as well as preliminary anti-cancer activity of oral CUDC-907 in patients with relapsed/ refractory lymphoma or MM. As of the April 27, 2015 data cut-off for the ASCO presentation, a total of 57 patients had been enrolled in the study, with 40 and 17 patients in the dose escalation and expansion phases of the study, respectively. In the completed dose escalation phase, patients either received CUDC-907 daily (QD, doses: 30 or 60 mg), or intermittently on twice weekly (BIW) or thrice weekly (TIW) schedules (daily doses: 60, 90, 120 or 150 mg), or on a 5 days on, 2 days off (5/2) schedule (dose: 60 mg). In the ongoing expansion phase, patients either receive CUDC-907 60 mg on the 5/2 schedule or 120 mg on the TIW schedule.
Low grade (Grade 1 and 2) diarrhea, fatigue and nausea were the most common drug related adverse events (AEs) reported in the study. Diarrhea and hyperglycemia are the only dose limiting toxicities (DLTs) reported. A total of 4 of these DLTs occurred in 3 patients treated at the highest doses on the QD (60 mg) and intermittent schedules (150 mg BIW and TIW). Other drug related Grade 3 or 4 AEs reported in 2 or more patients included thrombocytopenia and neutrophil decrease (hematologic AEs) as well as diarrhea, hyperglycemia and fatigue (non-hematologic AEs). The recommended Phase 2 dose of 60 mg 5/2 was reasonably well tolerated and is currently undergoing further examination in the expansion phase of the trial in patients with relapsed/ refractory DLBCL.
Forty-four of the 57 patients included in the ASCO presentation were evaluable for response assessment per protocol. Of the 16 patients with DLBCL enrolled across the dose escalation and expansion phases of the study, 10 were evaluable for disease response at the time of data cut-off. The best responses observed in these patients were CR (2 patients), PR (4 patients) SD (2 patients) and progressive disease, or PD (2 patients), with median duration on treatment of 3 months (range: 1.4-24.2 months, ongoing). The overall median duration on treatment for these 16 patients was 50 days. Objective responses were observed in patients with different subtypes of DLBCL, including germinal center B cell lymphoma (GCB) as well as in 3 patients with t-FL/ DLBCL.
|Indication||N||Best Response, N (%)||Median Treatment|
|CR||PR||SD||PD||NE**||Duration, days (range)|
|All DLBCL*||16||2 (13)||4 (25)||2 (13)||2 (13)||6 (38)||50 (5-727+)|
|> t-FL/DLBCL||7||1 (14)||2 (29)||2 (29)||—||2 (29)||96 (5-287+)|
|HL||14||—||1 (7)||8 (57)||3 (21)||2 (14)||106 (7-271+)|
|MM||9||—||—||4 (44)||2 (22)||3 (33)||71 (43-825+)|
|Other lymphoma||18||—||—||11 (61)||5 (28)||2 (11)||60 (17-468+)|
|Total||57||2 (4)||5 (9)||25 (44)||12 (21)||13 (23)||71 (5-825+)|
|* Includes t-FL/DLBCL and DLBCL|
|**44 patients were evaluable for disease response as of the April 27, 2015 data cut-off. NE includes patients who received less than 1 cycle of treatment (N=12) and one patient who has yet to be re-staged. Withdrawal from treatment during Cycle 1 was due to toxicity / AE (N=5), physician decision (N=3), PD (N=3) or withdrawal of consent (N=1).|
Consistent with preclinical observations, pharmacokinetic analysis shows significant levels of CUDC-907 in tumor tissue obtained from one patient. Pharmacodynamic analyses of the peripheral blood mononuclear cells isolated from patients show consistent modulation of HDAC and PI3K pathways, as demonstrated by increased levels of acetylated of histone H3 and decreased levels of phosphorylated AKT proteins. Further pharmacokinetic and pharmacodynamic analyses are ongoing. (Original Source)
Shares of Curis Inc. opened today at $3.39 and are currently trading up at $3.4. CRIS has a 1-year high of $3.50 and a 1-year low of $1.09. The stock’s 50-day moving average is $2.90 and its 200-day moving average is $2.28.
On the ratings front, Robert W. Baird analyst Brian Skorney reiterated a Buy rating on CRIS, with a price target of $5, in a report issued on April 20. The current price target implies an upside of 47.1% from current levels.
According to TipRanks.com, Skorney has a total average return of 18.4%, a 66.7% success rate, and is ranked #202 out of 3610 analysts.
Curis Inc is abiotechnology company engaged in developing and commercializing drug candidates for the treatment of human cancers. Its products includeCUDC-907,phosphatidylinositol-3-kinase andsmall molecule inhibitor of histone deacetylase.