Date: 2015-11-12
Type of information: Clinical research agreement
Compound: Lynparza™ (olaparib) and CRLX101 - poly-CD-PEG-camptothecin
Company: Cerulean Pharma (USA - MA) AstraZeneca (UK) National Cancer Institute (NCI) (USA)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism: poly ADP-ribose polymerase (PARP) inhibitor/enzyme inhibitor/topoisomerase inhibitor. CRLX101 is a dynamically tumor-targeted nanoparticle-drug conjugate (NDC) designed to concentrate in tumors and slowly release its anti-cancer payload, camptothecin, inside tumor cells. CRLX101 inhibits topoisomerase 1 (topo 1), which is involved in cellular replication, and hypoxia-inducible factor-1? (HIF-1?), which research suggests is a master regulator of cancer cell survival mechanisms thought to promote drug and radiation resistance. CRLX101 has shown activity in four tumor types in late stage disease and in a front line setting, and it has shown activity as monotherapy and in combination with other cancer treatments. CRLX101 is currently in Phase 2 clinical development and has been dosed in more than 250 patients. Lynparza™ (olaparib) is an oral poly ADP-ribose polymerase (PARP) inhibitor that exploits tumour DNA repair pathway deficiencies to preferentially kill cancer cells. Lynparza™ is the first PARP inhibitor to be approved for patients with germline BRCA-mutated advanced ovarian cancer, and has been launched in the U.S. and Europe. In addition to ovarian cancer, AstraZeneca is investigating the full potential of olaparib in multiple tumour types, with Phase III studies in second line gastric cancer, BRCA-mutated pancreatic cancer and adjuvant and metastatic BRCA-mutated breast cancers underway. The scientific rationale for combining PARP inhibitors with Top1 inhibitors is well understood. Simply stated, Top1 inhibitors damage DNA, and PARP inhibitors prevent DNA damage repair.
Disease: small cell lung cancer
Details: * On November 17, 2015, Cerulean Pharma announced that it has entered into a collaboration with AstraZeneca and the National Cancer Institute (NCI), part of the National Institutes of Health, to study Lynparza™ (olaparib) and CRLX101. The collaboration will explore the synergistic effects of AstraZeneca's Lynparza™, a poly ADP ribose polymerase (PARP) inhibitor, and CRLX101, Cerulean's inhibitor of topoisomerase 1 (Top1). The NCI will conduct a combination Phase I/IIa trial in the Branch led by Yves Pommier, M.D., Ph.D., Chief of the Developmental Therapeutics Branch. Under this collaboration, AstraZeneca will supply Lynparza™, Cerulean will supply CRLX101, and the NCI will fund and conduct the clinical trial under Cooperative Research and Development Agreements with the companies. The clinical trial of Lynparza™ in combination with CRLX101 in small cell lung cancer will enroll approximately 55 patients with enrollment expected to commence in the first half of 2016.
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