MIPS partner, Starpharma, announces positive phase 1 clinical results for DEP® Docetaxel
11 October 2017
Scientists within Professor Chris Porter’s group at the ARC Centre of Excellence for Convergent Bio-Nano Science and Technology at the Monash Institute of Pharmaceutical Science have been working for a number of years with the Australian Biotechnology company, Starpharma, to develop advanced drug delivery systems. One result of those programs has been the development of the DEP® delivery platform with broad application including for improved cancer treatments. The DEP® delivery technology, based on Starpharma’s star-shaped polymers or dendrimers, has been shown to improve drug efficacy and reduce toxicity in a number of pre-clinical oncology models. Starpharma has applied this technology in its own development programs (such as DEP® docetaxel) and in partnership with pharmaceutical companies, for example AstraZeneca (see http://starpharma.com/news/340).
In an exciting recent development Starpharma announced on 22 September that its phase 1 trial for DEP® docetaxel has achieved the key objective of determining a Recommended Phase 2 Dose (RP2D), with no reports of protocol-defined dose limiting toxicities (DLTs). The trial also demonstrated that the DEP® platform was able to prevent the dose limiting toxicity of docetaxel, neutropenia. The trial has now been adapted to transition seamlessly into phase 2, with ethics and regulatory approvals already granted, and recruitment and patient screening activities underway for this next phase.
The phase 1 trial enrolled 27 patients with advanced solid cancers, including lung (small cell and non-small cell), prostate, pancreatic, gastro-oesophageal, breast, cervical, renal and brain. Patients received DEP® docetaxel at a range of doses providing the equivalent of 10‑105 mg/m2 docetaxel. Throughout the phase 1 trial, patients were treated with up to six cycles of DEP®docetaxel. Due to the lack of protocol-defined DLTs for DEP® docetaxel, a formal Maximum Tolerated Dose (MTD) was not determined.
The PK characteristics of DEP® docetaxel vary from conventional docetaxel formulations (e.g. Taxotere®), whereby every milligram of docetaxel that is dosed as DEP® docetaxel results in significantly greater exposure to docetaxel than with conventional formulations like Taxotere®. That is, when equivalent doses of DEP® docetaxel and conventional docetaxel formulations are intravenously administered to patients, DEP® docetaxel achieves a much greater exposure to the cancer drug, docetaxel, through its extended half-life.
Despite most trial patients having not responded to or relapsed following previous anti-cancer therapies (i.e., heavily pre-treated prior to enrolment into the trial), encouraging signs of anti-cancer efficacy, including stable disease, were observed in approximately half of the DEP® docetaxel-treated patients for a range of tumour types, including cancers that do not typically respond to docetaxel.
Commenting on the results, Starpharma CEO, Dr Jackie Fairley, said, “It is very exciting to see these phase 1 results for DEP®docetaxel and to move to phase 2. As well as the very promising signs of efficacy observed, what is truly remarkable is that there was not a single report of neutropenia amongst patients dosed with DEP® docetaxel. Neutropenia is a life-threatening side-effect that usually affects more than 90% of Taxotere® patients and often limits the dose that patients can receive.”
“We are also delighted that no hair loss with DEP® docetaxel was reported apart from one patient who experienced a mild case of alopecia. Publications indicate that this side effect is one of the most feared side-effects of cancer treatment. The reduction in these significant side-effects and others such as anaemia, diarrhoea and anaphylaxis means that DEP® docetaxel has the potential to have a positive impact on the quality of life of cancer patients undergoing treatment. This profile also makes DEP® docetaxel an attractive product to combine with other anti-cancer therapies that cause bone marrow toxicity and other toxicities not seen with DEP® docetaxel.”
For more details see http://starpharma.com/news/339