• Phase 1 part of the DEP^® cabazitaxel phase 1 / 2 trial has been successfully completed, with phase 2 to commence immediately
• Encouraging efficacy signals:
  • were observed in 67% of patients assessed to date
  • included prolonged stable disease in multiple tumour types, such as prostate cancer
  • were observed in cancers not usually responsive to conventional cabazitaxel (Jevtana^®), such as ovarian cancer, and at doses lower than used for Jevtana^®
• DEP^® cabazitaxel patients experienced significantly fewer side effects such as nausea and bone marrow toxicity (neutropenia, anaemia, thrombocytopenia) than are typically seen with conventional cabazitaxel (Jevtana^®), and no anaphylaxis or hypersensitivity reactions were observed
• Recruitment into the phase 2 part of the trial is now underway with two new trial sites being added – Imperial College London and Velindre Cancer Centre in Cardiff

Melbourne, Australia; 10 December 2019: Starpharma (ASX: SPL, OTCQX: SPHRY) today announced successful completion of the phase 1 component of its phase 1 / 2 trial for DEP^® cabazitaxel. The trial met its objective of evaluating safety, tolerability and preliminary efficacy data, and identifying a recommended phase 2 dose of 20 mg/m². The trial will now transition seamlessly into phase 2, with two new sites initiated and recruitment activities already underway.

The phase 1 part of the trial enrolled 14 patients with a range of cancers, including prostate, ovarian, cholangiocarcinoma and pancreatic cancer. Efficacy signals were observed in 67% of evaluable[1] patients and included prolonged stable disease (>47 weeks) and significant reductions in specific tumour biomarkers such as prostate specific antigen (PSA).

Efficacy signals were seen in a range of tumour types including prostate, ovarian, cholangiocarcinoma and pancreatic cancer. Furthermore, efficacy signals in prostate cancer were observed at doses up to 40% lower than usually used for standard cabazitaxel (Jevtana^®). Jevtana^® is approved for the treatment of prostate cancer, but ovarian, pancreatic, and cholangiocarcinoma are not currently approved indications.

These efficacy signals are particularly encouraging given all patients in the study were heavily pre-treated and had either progressed or had stopped responding to prior anti-cancer therapies to qualify for entry into the DEP^® cabazitaxel study. Most patients in the trial had been previously treated with multiple cancer therapies, including taxane chemotherapies such as Taxotere^®, Jevtana^® (cabazitaxel), and Abraxane^®, with some patients having received up to 33 cycles of treatment and up to 10 different treatments before entering the DEP^® cabazitaxel trial. One prostate cancer patient who had been unable to tolerate conventional treatment (Taxotere^®) due to dose-limiting severe neutropenia received 15 cycles of DEP^® cabazitaxel without neutropenia and experienced >47 weeks’ stable disease.

DEP^® cabazitaxel trial participants experienced significantly fewer side effects, such as bone marrow toxicity (neutropenia, anaemia, thrombocytopenia), anorexia, and vomiting, than are typically seen with Jevtana^®. Participants did not require anti‑nausea, antihistamine or cortisone pre-treatments, as is standard for Jevtana^®. There were no cases of hypersensitivity or anaphylaxis.

Commenting on the results, Starpharma CEO, Dr Jackie Fairley, said, “We’re pleased to advance our second DEP^® product to phase 2, and are very excited to see the promising efficacy signals observed in such a resistant patient cohort, and the remarkably low incidence of adverse events, including bone-marrow toxicity/neutropenia, with DEP^® cabazitaxel. We look forward to sharing these results with commercial partners.”

Recruitment and patient screening activities are now underway in the phase 2 study and two additional trial sites in the UK are being opened, taking the total number of sites to four. These additional sites are the Velindre Cancer Centre in Cardiff and Imperial College London. Other sites are currently under consideration including in Australia.

Phase 1 trial results

A total of 14 patients were enrolled into the phase 1 part of the study and received DEP^® cabazitaxel at a range of doses between 2 mg/m² to 25 mg/m².  Throughout the phase 1 part of the trial, patients were treated with up to 15 cycles of DEP^® cabazitaxel. Patients dosed with DEP^® cabazitaxel required no steroid, antihistamine or anti-emetic pre-treatment.

Efficacy Signals

Whilst the primary objective of the phase 1 part of the trial was not a formal evaluation of efficacy, and patients were typically heavily pre-treated with other cancer agents, encouraging signs of efficacy were observed in 67% patients treated with DEP^® cabazitaxel that were evaluable for treatment response. Evaluable patients are those patients who have received ≥1 dose DEP^® cabazitaxel and have had a tumour assessment conducted post treatment.

The efficacy signals observed included prolonged stable disease in multiple patients and in a variety of cancer types, including prostate, ovarian, cholangiocarcinoma and pancreatic. Substantial tumour shrinkage was observed for a number of patients as well as marked decreases in specific tumour biomarkers. One patient with prostate cancer experienced stable disease for more than 47 weeks and a reduction in PSA of 79%. One stage IV ovarian cancer patient who had received more than 30 cycles of five different previous treatments (including paclitaxel) was administered seven cycles of DEP^® cabazitaxel in the trial and achieved a reduction in tumour biomarker (CA-125) of 56%. One patient with stage III cholangiocarcinoma (the second most common liver cancer which is often fatal) achieved a 76% decrease in a tumour biomarker after two cycles of DEP^® cabazitaxel.

Safety and Tolerability

Patients treated with DEP^® cabazitaxel experienced significantly less toxicity than is usually associated with Jevtana^®, including less bone marrow toxicity (neutropenia, anaemia, thrombocytopenia), anorexia and vomiting. No cases of hypersensitivity or hair-loss were observed with DEP^® cabazitaxel treatment.

The vast majority of adverse events (AEs) reported were mild (grade 1). All the AEs observed with DEP^® cabazitaxel are seen with conventional cabazitaxel (Jevtana^®) and were reported at a comparable or lower rate than Jevtana^®. The most frequently reported AEs with DEP^® cabazitaxel included fatigue, nausea, and at the highest doses, neutropenia.

The selection of the recommended phase 2 dose (RP2D) of DEP^® cabazitaxel was determined taking account of the overall safety, tolerability, pharmacokinetics and preliminary efficacy results for DEP^® cabazitaxel in the trial. The RP2D has been confirmed as 20 mg/m² cabazitaxel equivalents administered intravenously once every three weeks.

Phase 2 clinical trial

The phase 2 part of the DEP^® cabazitaxel trial is being conducted at multiple sites, including Guy’s Hospital in London, University College London, the Velindre Cancer Centre in Cardiff and Imperial College London. Recruitment activities, including patient screening, for phase 2 have already commenced and Starpharma is also exploring opportunities to initiate further sites to expedite recruitment.

The phase 2 study is an open-label trial, with the objective of establishing anti-tumour activity (efficacy) and safety of DEP^® cabazitaxel at the RP2D of 20 mg/m². The first stage will enrol approximately 20 patients with a variety of cancers, including prostate cancer. The study will further explore efficacy in selected tumour types and recruitment numbers may be adjusted based on results in certain patient cohorts.

DEP^® cabazitaxel is one of Starpharma’s clinical stage DEP^® assets being developed internally, alongside DEP^® docetaxel and DEP^® irinotecan. Starpharma’s intention is to licence internal DEP^®  assets following clinical proof-of-concept. Starpharma also has partnered DEP^® programs including a multiproduct DEP^® licence with AstraZeneca, which includes the development and commercialisation of two novel oncology compounds - one of which (AZD0466, a novel Bcl2/xL inhibitor) is expected to enter the clinic shortly.

About DEP^® cabazitaxel

DEP^® cabazitaxel is a patented, detergent free, nanoparticle version of the cancer drug, Jevtana^®, and is currently in phase 2. Jevtana^® is a leading oncology agent used to treat advanced prostate cancer and is also under development for other cancers including testicular, ovarian, breast, and head and neck. The  current (non-dendrimer) formulation of the product has US Food and Drug Administration (FDA)-mandated ‘black box’ warnings in relation to neutropenia, which is a major dose limiting side effect, and severe hypersensitivity (e.g. anaphylaxis) resulting from the polysorbate-80 detergent excipient used in its formulation.

Patients treated with conventional cabazitaxel (Jevtana^®) are routinely pre-treated with corticosteroids and antihistamines to reduce the risk of life-threatening anaphylactic reactions to the excipients (detergents) present in conventional cabazitaxel. Starpharma’s DEP^® cabazitaxel is water soluble, eliminating the need for steroid and antihistamine pre-treatment and reduces the risk of anaphylactic reactions. 

Download ASX Announcement: DEP cabazitaxel progresses to phase 2 on positive results (pdf, 306kb)

[1] Evaluable patients are those patients who have received ≥1 dose DEP^® cabazitaxel and have had a tumour assessment conducted post treatment to determine radiological and/or biochemical response. To date, nine patients are considered to be evaluable for efficacy, and several patients are at an earlier stage of their treatment and are yet to undergo an efficacy assessment.