Starpharma (ASX:SPL) has announced 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 company said the trial has now been adapted to transition into phase 2, with ethics and regulatory approvals already granted, and recruitment and patient screening activities underway.
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.
According to Starpharma, 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, the company said 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.
“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,” said CEO Dr Jackie Fairley.
“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.”
The phase 2 study is as an open-label, two-stage design, with the objective of establishing efficacy and safety of DEP docetaxel at the RP2D of 60 mg/m2. The first stage will enrol approximately 20 patients with lung or prostate cancer, which are key approved indications for docetaxel (Taxotere). It is intended that the second stage of the trial will enrol a further 20 patients with tumour types selected based on results from the first stage.
In parallel, Starpharma said it will also investigate the potential benefits of combining DEP docetaxel with another anticancer agent, nintedanib (Vargatef), which is approved for treatment of lung cancer in combination with docetaxel (Taxotere). Up to an additional 12 patients are expected to be enrolled in this arm of the trial.