US-based, clinical-stage company Cerulean Pharma has dosed the first patient in a Phase l/ll clinical trial of its lead nanoparticle-drug conjugate NDC candidate, CRLX101, in combination with lynparza (olaparib) in patients with advanced solid tumours.
The open-label, single centre trial is being conducted by the National Cancer Institute (NCI), US, along with AstraZeneca and Cerulean.
The trial is led by NCI investigators, Dr Anish Thomas and Dr Yves Pommier.
In pre-clinical studies, CRLX101 causes transient DNA damage in bone marrow and sustained DNA damage in tumours, consistent with the prolonged circulation and tumour targeting of CRLX101.
By having a proper dosing schedule of CRLX101 and lynparza, Cerulean expects to mitigate much of the combined bone marrow toxicity in the clinic, while achieving a combination benefit.
Lynparza is a new oral poly ADP-ribose polymerase (PARP) inhibitor that exploits tumour DNA repair pathway deficiencies to preferentially kill cancer cells.
CRLX101 is a NDC, which is designed to concentrate on tumours and slowly release its anti-cancer payload, camptothecin, inside tumour cells.
Currently, CRLX101 is in Phase ll clinical development and has been dosed in more than 350 patients.
The Phase l portion of CRLX101 and lynparza combination trial will enrol up to 30 patients with advanced solid tumours that are resistant or refractory to standard therapy.
The trial is designed to identify the maximum tolerated dose, or recommended Phase ll dose of CRLX101 when combined with lynparza, and to provide more data on pharmacokinetics, pharmacodynamics and safety.
Cerulean Pharma president and chief executive officer Christopher Guiffre said: "We currently are combining CRLX101 with angiogenesis inhibitors, chemotherapy, and now a PARP inhibitor, which speaks to the broad potential applicability and combinability of our NDCs.
"This trial represents our first step in a new frontier for CRLX101: DNA Damage Response.
"We look forward to top-line data from this trial in the first half of 2017."