Cerulean Announces First Patient Dosed in Phase 1b/2 Trial of CRLX101 in Combination with Chemotherapy and Radiation in Neoadjuvant Rectal Cancer

CAMBRIDGE, Mass., March 18, 2014 /PRNewswire/ -- Cerulean Pharma Inc., a leader in dynamically tumor-targeted nanopharmaceuticals, today announced that the first patient has been dosed in a Phase 1b/2 trial designed to (1) identify the recommended Phase 2 dose of CRLX101 in combination with Xeloda^® (capecitabine) and radiation (chemoradiotherapy) and (2) detect signals, if any, of increased efficacy over standard neoadjuvant chemoradiotherapy for rectal cancer. The trial is investigator-initiated and is being conducted at the University of North Carolina Lineberger Comprehensive Cancer Center and affiliated sites. This is an open label, single arm trial designed to enroll up to 53 patients, with a primary endpoint of pathologic complete response rate (pCR) and secondary endpoints of safety, disease free survival, and overall survival.

The majority of rectal cancer patients are diagnosed before disease has metastasized to distant sites. Patients who are diagnosed prior to metastasis are candidates for pre-surgical, or "neoadjuvant," therapy of 5 to 6 weeks of 5-FU or its pro-drug, capecitabine, plus radiation, to shrink the tumors as much as possible prior to surgery. pCR is observed in approximately 15% to 20% of rectal cancer patients treated in a neoadjuvant setting and is associated with compelling long-term disease free and overall survival, with low rates of local recurrence and distant failure.  

According to Cerulean's Chief Medical Officer, Edward Garmey, M.D., "Radiotherapy causes DNA strand breaks which, if not repaired, lead to desired apoptosis of radiated tumor cells. However, cell repair mechanisms, including topoisomerase 1 (topo 1), can undo the radiation damage to tumor cells and interfere with the desired effects of the radiation therapy." 

CRLX101 is a dual inhibitor of hypoxia-inducible factor-1a (HIF-1a) and topo 1. In pre-clinical models, CRLX101 has shown synergy with radiotherapy and VEGF inhibitors, including Avastin^® (bevacizumab). In addition, in an ongoing Phase 1b/2 clinical trial, the combination of CRLX101 and Avastin appears well-tolerated in late-stage renal cell carcinoma patients while demonstrating signals of efficacy.

"It is precisely because of the dual knockdown of topo 1 and HIF-1a that we are so interested in this combination of CRLX101 with chemoradiotherapy," said the trial's principal investigator, Andrew Wang, M.D., adding that "HIF-1a is known to be upregulated after radiotherapy, and there is preclinical evidence suggesting that activated HIF-1a can promote resistance to radiotherapy."  

About CRLX101
CRLX101 is an investigational anti-cancer agent that inhibits topoisomerase 1 (topo 1) and hypoxia-inducible factor-1a (HIF-1a). Topo 1 is an essential cell replication enzyme and a commercially validated anti-cancer target. HIF-1a 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-1a 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.

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SOURCE Cerulean Pharma Inc.