“Sunesis Pharmaceuticals, Inc. (Nasdaq: SNSS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel small-molecule therapeutics, announced positive interim data from the company’s ongoing Phase 2 clinical trial of its lead product candidate, SNS-595, in platinum-resistant ovarian cancer patients.
In this Phase 2 clinical trial, single agent SNS-595 has demonstrated disease control (defined as stable disease, partial response or complete response) in 31 of 35 patients evaluable for best response using GOG-RECIST criteria. Of these 31 patients, one patient had a complete response, four patients had partial responses (two unconfirmed) and 26 patients had a best response of stable disease. All patients enrolled in the trial have previously failed treatment with platinum-containing regimens, and fourteen of the 35 patients have also failed prior treatment with doxorubicin HCl liposome injection (Doxil(R)). Both platinum-resistant and Doxil-resistant patients in the Phase 2 clinical trial have responded to SNS-595 therapy.
‘Recurrence rates among ovarian cancer patients remain high, and the majority of refractory patients are resistant to platinum-based therapies. Based on these interim data, SNS-595 appears to be a promising, active agent in a difficult-to-treat ovarian cancer patient population,’ said William P. McGuire, M.D., Medical Director of the Harry and Jeanette Weinberg Cancer Institute at Franklin, and a lead investigator for the Phase 2 trial.
Among forty-five patients with sufficient follow-up to yield safety data, SNS-595 was generally well tolerated at a dose level of 48mg/m2 administered once every three weeks. The most common adverse events reported thus far include nausea, fatigue, vomiting and alopecia. There was a low rate of febrile neutropenia or other Grade 3/4 adverse events, and manageable Grade 1/2 nausea or vomiting.
Based on the indications of clinical activity and the acceptable tolerability profile demonstrated to date among this patient population, the dose of SNS-595 in this trial has been increased to 60 mg/m2 over twenty-eight days. Patient accrual at this dose level is ongoing.
‘We are pleased by the strong signal of activity emerging from our Phase 2 clinical trial of SNS-595 at the 48mg/m2 dose level. Based on the drug’s observed safety profile and recommendations from advisors, we are exploring a higher dose of SNS-595 in this trial. Enrollment has begun at 60 mg/m2 and we expect to enroll approximately 30 patients at this dose by the third quarter of this year,’ said Daniel C. Adelman, M.D., Senior Vice President, Development and Chief Medical Officer of Sunesis. ‘Enthusiasm for SNS-595 among our clinical investigators is growing and enrollment in this trial has been accelerating. We expect to present further data from this Phase 2 clinical trial this year.’
The interim clinical results are being presented in a poster, “A Phase 2 Trial of SNS-595 in Women with Platinum-Refractory Epithelial Ovarian Cancer” (Abstract # 290), at the 39th Annual Meeting on Women’s Cancer hosted by the Society of Gynecologic Oncologists (SGO) in Tampa, Fla. through March 12, 2008.”
SNS-595 is a novel naphthyridine analog, structurally related to quinolones, a class of compounds which has not been used previously for the treatment of cancer. SNS-595 is a specific DNA intercalator and topoisomerase II poison, causing replication-dependent site-selective double strand DNA damage, irreversible G2 arrest and rapid apoptosis. In non-clinical evaluations, SNS-595 demonstrates broad and potent activity in xenograft, syngeneic and drug-resistant models. In addition to the Phase 2 clinical trial in ovarian cancer patients, SNS-595 is currently being evaluated in combination with cytarabine in a Phase 1b acute leukemia clinical trial. In clinical trials conducted to date, SNS-595 has been generally well tolerated and has shown objective responses in both solid and hematologic tumor types.”
Quoted Source: [“Sunesis Pharmaceuticals Reports Positive Interim Data for SNS-595 Single-Agent Activity in Platinum-Resistant Ovarian Cancer”, MedicalNewsToday.com, March 11, 2008. (Emphasis added by posting author)].
- Open Recruiting for SNS-595 Phase II Clincial Trial entitled, “A Phase 2 Open-Label, Multicenter Study of SNS-595 Injection in Patients With Platinum-Resistant Ovarian Cancer.”
- “Sunesis Pharmaceuticals Presents Nonclinical Data on SNS-595 at the Annual Meeting of the American Association for Cancer Research — Nonclinical Studies Demonstrate that SNS-595 Acts through a Dual Mechanism and May Evade Common Drug Resistance Mechanisms Research Supports Current Clinical Development of SNS-595 in AML and Ovarian Cancer and Potential in Additional Indications,” Sunesis Pharmaceuticals Press Release dated April 14, 2008. PDF document download of 2008 AACR Annual Meeting Presentation Re SNS-595 (Poster 2830).
- “A Phase 2 Trial of Voreloxin (Formerly SNS-595) in Women with Platinum-Resistant Epithelial Ovarian Cancer,” 2008 American Society of Clinical Oncology Annual Meeting Presentation, May 31, 2008 (Adobe Reader PDF Document). See also, “A phase II trial of SNS-595 in women with platinum resistant epithelial ovarian cancer,” W. P. McGuire et. al., J Clin Oncol 26: 2008 (May 20 suppl; abstr 5582).