Cerulean Pharma, a leader in dynamic tumour targeting, has signed a clinical research agreement with the GOG Foundation Inc. to conduct an open-label phase 1b clinical trial of its lead product candidate, CRLX101, in combination with weekly paclitaxel in patients with relapsed ovarian cancer.

Cerulean and the GOG Foundation have commenced start-up procedures and expect to enroll the first patient in the second quarter of 2015. This trial is being conducted by Cerulean in collaboration with the GOG Foundation under the direction of principal investigator Carolyn N. Krasner, MD, of the Massachusetts General Hospital Cancer Center.

"Cerulean is expanding the clinical development of CRLX101 in relapsed ovarian cancer by initiating a phase 1b trial of CRLX101 plus weekly paclitaxel in collaboration with the GOG Foundation," says Paul Friedman, MD, executive chairman at Cerulean. "We continue to study CRLX101 in combination with Avastin, and given the changing landscape in relapsed ovarian cancer resulting from the FDA's recent approval of Avastin in combination with three chemotherapies, we have decided to explore an additional combination with CRLX101 in relapsed ovarian cancer."

Paclitaxel, a widely used chemotherapy in the treatment of metastatic ovarian cancer, has anti-angiogenic properties which can induce hypoxic conditions, leading to the up-regulation of HIF-1a, causing tumours to develop drug resistance. Preclinical data demonstrate that CRLX101 reduces the up-regulation of HIF-1a, and may sensitise tumours that have become resistant to previous therapy.

This is a phase 1b multi-centre, open-label, dose-escalation study of CRLX101 in combination with weekly paclitaxel in up to 18 patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer. The trial is designed to identify the maximum tolerated dose (MTD) as well as pharmacokinetics, safety and tolerability of CRLX101 in combination with weekly paclitaxel. Preliminary evidence of efficacy will also be evaluated.

The GOG Foundation, Inc. (GOG Foundation) is an independent international non-profit organisation with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies. The GOG Foundation is committed to maintaining the highest standards in clinical trials development, execution, analysis and distribution of results. Continuous evaluation of our processes is utilised in order to constantly improve the quality of patient care. The GOG Foundation conducts clinical trials for patients with a variety of gynaecologic malignancies, including cancers that arise from the ovaries, uterus, cervix, vagina, and vulva. The GOG Foundation is a separate entity from the National Clinical Trials Network groups that are funded by the National Cancer Institute.

CRLX101 is a dynamically tumour-targeted nanoparticle-drug conjugate (NDC) designed to concentrate in tumours 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-1a (HIF-1a), 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 different tumour types, both 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.

CRLX301 is a dynamically tumour-targeted NDC designed to concentrate in tumours and slowly release its anti-cancer payload, docetaxel, inside tumour cells. In preclinical studies, CRLX301 delivers up to 10 times more docetaxel into tumours, compared to an equivalent milligram dose of commercially available docetaxel and was superior to docetaxel in seven of seven animal models, with a statistically significant survival benefit seen in five of those seven models. In addition, preclinical data show that CRLX301 had lower toxicity than has been reported with docetaxel in similar preclinical studies. CRLX301 is currently in phase 1 clinical development.

The Cerulean team is committed to improving treatment for people living with cancer. We apply our Dynamic Tumour Targeting Platform to create a portfolio of NDCs designed to selectively attack tumor cells, reduce toxicity by sparing the body's normal cells, and enable therapeutic combinations. Our first platform-generated candidate, CRLX101, is in multiple clinical trials in combination with other cancer treatments, all of which aim to unlock the power of combination therapy. Our second platform-generated candidate, CRLX301, is in a phase 1/2a clinical trial.

Cerulean's Dynamic Tumour Targeting Platform creates NDCs that are designed to provide safer and more effective cancer treatments. We believe our NDCs concentrate their anti-cancer payloads inside tumours while sparing normal tissue because they are small enough to pass through the "leaky" vasculature present in tumours but are too large to pass through the wall of healthy blood vessels. Once inside tumors, our NDCs enter tumour cells where they slowly release anti-cancer payloads from within the tumour cells.