Cerulean Announces First Patient Dosed in Phase 2 Clinical Trial of CRLX101 in Combination with Avastin in Relapsed Ovarian Cancer
CAMBRIDGE, Mass. - February 11, 2014 - Cerulean Pharma Inc., a leader in dynamically tumor-targeted nanopharmaceuticals, today announced that the first patient has been dosed in an open label single-arm Phase 2 clinical trial of its lead candidate, CRLX101, in combination with Avastin (bevacizumab) in patients with relapsed ovarian cancer.
The Phase 2 combination therapy trial of this investigational treatment is being conducted at Massachusetts General Hospital (MGH) and the affiliated Harvard teaching hospitals under the direction of principal investigator Carolyn Krasner, M.D. The trial will investigate the rate of progression free survival at six months (PFS6) using RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 criteria in relapsed ovarian cancer patients treated with a combination of Avastin and CRLX101.
Neither CRLX101 nor Avastin is approved for the treatment of ovarian cancer. In a 29-patient single-arm Phase 2 monotherapy trial at the same hospitals, CRLX101 demonstrated single agent activity in previously treated late-stage ovarian cancer patients with multiple RECIST partial responses and the satisfaction of the primary efficacy endpoint of at least four of 29 patients achieving PFS6. In this CRLX101 monotherapy trial, the adverse events were generally low grade and manageable.
“When ovarian cancer recurs, it can be very difficult to treat because of increasing resistance to chemotherapy,” said Dr. Krasner. “Based on our experience with CRLX101 in monotherapy, we are excited to transition into a CRLX101-Avastin combination trial to assess if pre-clinical synergies observed with the two agents translate into meaningful benefit for platinum resistant patients.”
CRLX101 inhibits hypoxia-inducible factor-1α (HIF-1α) and topoisomerase-1. In pre-clinical models, CRLX101 has shown synergy with VEGF inhibitors, including Avastin. In an ongoing Phase 1b/2a clinical trial at the University of Pennsylvania, the combination of CRLX101 and Avastin at their respective maximum tolerated doses appears well-tolerated in late-stage renal cell carcinoma (RCC) patients while demonstrating signals of efficacy. The safety data from the RCC trial were considered by the MGH Institutional Review Board in approving use of the combination for ovarian cancer patients treated in this clinical trial.
“We are excited to embark on this latest trial of CRLX101,” said Edward Garmey, M.D., chief medical officer of Cerulean. “In the past few months, preliminary results from an ongoing clinical trial in renal cell carcinoma suggest synergies between CRLX101 and Avastin. We are pleased to collaborate with Dr. Krasner to investigate this promising potential treatment for relapsed ovarian cancer. And we appreciate Roche-Genentech’s support of this trial by providing the Avastin to be used in combination with CRLX101.”
CRLX101 is an investigational anti-cancer agent that inhibits topoisomerase 1 (topo 1) and hypoxia-inducible factor-1α (HIF-1α). Topo 1 is an essential cell replication enzyme and a commercially validated anti-cancer target. HIF-1α is a master regulator of cancer cell survival mechanisms such as cancer stem cell formation and is upregulated under hypoxic conditions created by traditional cancer therapies, for example anti-angiogenic agents and radiation.
To date, HIF-1α has been undruggable. CRLX101 is a dynamically tumor-targeted nanopharmaceutical designed to concentrate in tumors and release its payload, camptothecin, over an extended period of time, prolonging drug exposure at the site of action. CRLX101 has been dosed in more than 200 patients, many for more than six months. Anti-tumor activity (multiple RECIST responses and prolonged stable disease) has been observed in three different tumor types in highly refractory treatment settings, as monotherapy and in combination with Avastin®. CRLX101 is currently in Phase 2 clinical development.
More information on CRLX101 clinical trials can be found at www.clinicaltrials.gov.
About Cerulean Pharma Inc.
Cerulean Pharma Inc. is a clinical-stage company specializing in the development of dynamically tumor-targeted nanopharmaceuticals. Cerulean is applying its proprietary nanopharmaceutical platform to advance a new class of therapeutic agents to address significant unmet medical needs. With an initial focus in oncology, the Company’s technology platform can be applied to a wide range of drug molecules, ranging from small molecules to peptides and RNAs. Cerulean is privately held and located in Cambridge, Massachusetts.
For more information, please visit the Company’s website at http://www.ceruleanrx.com.
Source: Cerulean Pharma Inc.
Posted: February 2014