Starpharma Release: DEP Docetaxel Positive Phase I Results; Phase II Commences
• DEP® docetaxel phase 1 trial successfully completed with phase 2 to commence immediately
• DEP® docetaxel patients had no reports of neutropenia, a life-threatening toxicity seen in virtually all patients treated with conventional docetaxel formulations (e.g. Taxotere®)
• Encouraging signs of efficacy observed for multiple tumour types with DEP® docetaxel
• Improved pharmacokinetics (PK) of DEP® docetaxel were confirmed in the study showing a longer half life, lower peak blood concentration and extended exposure to docetaxel
• Phase 2 trial in lung and prostate cancer to commence immediately with DEP® docetaxel as a monotherapy, and in combination with nintedanib (Vargatef®) for lung cancer
Melbourne, Australia; 22 September 2017: Starpharma (ASX: SPL, OTCQX: SPHRY) today announced 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 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.”
Phase 1 trial results
Safety and Tolerability
Clear benefits of the DEP® technology were observed in the DEP® docetaxel trial. In particular there were no reports of neutropenia , the primary, life-threatening DLT that is reported to occur in virtually all patients receiving 60-100 mg/m2 of conventional docetaxel (Taxotere®). There was also a notable lack of reports of several other problematic adverse events (AEs) observed with docetaxel (e.g. Taxotere®) treatment, including anaphylaxis, fluid retention, diarrhoea and nail disorders. Only one patient treated with DEP® docetaxel experienced anaemia, a very common adverse event associated with docetaxel (Taxotere®) treatment. Furthermore, only one patient treated with DEP® docetaxel experienced a mild case of hair-loss (alopecia), a highly troubling side effect that is reported to occur in three-quarters of patients receiving docetaxel (Taxotere®), with recent reports indicating that such hair-loss can be permanent in some patients. The most frequently reported AEs observed with DEP® docetaxel included fatigue, rash, peripheral neuropathy, nausea, vomiting, decreased appetite and myalgia. All these AEs are seen with conventional docetaxel (e.g. Taxotere®) and were reported at a comparable or lower rate for DEP® docetaxel than seen with conventional formulations of docetaxel. The majority of these AEs were mild to moderate (grade 1 or 2).
As there were no protocol-defined DLTs in patients across all dose levels, no formal maximum tolerated dose (MTD) was established for DEP® docetaxel in the trial. Instead, the selection of the phase 2 dose (RP2D) of DEP® docetaxel was determined taking account of the overall safety, tolerability, PK and preliminary efficacy results for DEP® docetaxel in the trial. The RP2D has been confirmed as 60 mg/m2 docetaxel equivalents administered intravenously once every 3 weeks. Patients treated with conventional docetaxel formulations (e.g. Taxotere®) are routinely pre-treated with corticosteroids to reduce the risk of life threatening anaphylactic reactions to the excipients (detergents) that are present in conventional docetaxel formulations. Starpharma’s DEP® technology eliminates the need for these detergents as DEP® docetaxel is water soluble, thereby also eliminating the need for steroid pre-treatment in DEP® docetaxel patients, and reducing the risk of anaphylactic reactions.
• DEP® docetaxel patients had no reports of neutropenia, a life-threatening toxicity seen in virtually all patients treated with conventional docetaxel formulations (e.g. Taxotere®)
• Encouraging signs of efficacy observed for multiple tumour types with DEP® docetaxel
• Improved pharmacokinetics (PK) of DEP® docetaxel were confirmed in the study showing a longer half life, lower peak blood concentration and extended exposure to docetaxel
• Phase 2 trial in lung and prostate cancer to commence immediately with DEP® docetaxel as a monotherapy, and in combination with nintedanib (Vargatef®) for lung cancer
Melbourne, Australia; 22 September 2017: Starpharma (ASX: SPL, OTCQX: SPHRY) today announced 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 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.”
Phase 1 trial results
Safety and Tolerability
Clear benefits of the DEP® technology were observed in the DEP® docetaxel trial. In particular there were no reports of neutropenia , the primary, life-threatening DLT that is reported to occur in virtually all patients receiving 60-100 mg/m2 of conventional docetaxel (Taxotere®). There was also a notable lack of reports of several other problematic adverse events (AEs) observed with docetaxel (e.g. Taxotere®) treatment, including anaphylaxis, fluid retention, diarrhoea and nail disorders. Only one patient treated with DEP® docetaxel experienced anaemia, a very common adverse event associated with docetaxel (Taxotere®) treatment. Furthermore, only one patient treated with DEP® docetaxel experienced a mild case of hair-loss (alopecia), a highly troubling side effect that is reported to occur in three-quarters of patients receiving docetaxel (Taxotere®), with recent reports indicating that such hair-loss can be permanent in some patients. The most frequently reported AEs observed with DEP® docetaxel included fatigue, rash, peripheral neuropathy, nausea, vomiting, decreased appetite and myalgia. All these AEs are seen with conventional docetaxel (e.g. Taxotere®) and were reported at a comparable or lower rate for DEP® docetaxel than seen with conventional formulations of docetaxel. The majority of these AEs were mild to moderate (grade 1 or 2).
As there were no protocol-defined DLTs in patients across all dose levels, no formal maximum tolerated dose (MTD) was established for DEP® docetaxel in the trial. Instead, the selection of the phase 2 dose (RP2D) of DEP® docetaxel was determined taking account of the overall safety, tolerability, PK and preliminary efficacy results for DEP® docetaxel in the trial. The RP2D has been confirmed as 60 mg/m2 docetaxel equivalents administered intravenously once every 3 weeks. Patients treated with conventional docetaxel formulations (e.g. Taxotere®) are routinely pre-treated with corticosteroids to reduce the risk of life threatening anaphylactic reactions to the excipients (detergents) that are present in conventional docetaxel formulations. Starpharma’s DEP® technology eliminates the need for these detergents as DEP® docetaxel is water soluble, thereby also eliminating the need for steroid pre-treatment in DEP® docetaxel patients, and reducing the risk of anaphylactic reactions.