Starpharma today announced that it has received the necessary regulatory and ethics approvals and will  commence its phase 1/2 clinical trial for DEP^® irinotecan. The objectives of the trial are to evaluate the safety, tolerability and pharmacokinetics of DEP^® irinotecan to define a recommended phase 2 dose (RP2D), and to determine anti-tumour efficacy of the product in select tumour types. DEP^® irinotecan is the third DEP^® product to enter the clinic from Starpharma’s internal portfolio with a fourth, partnered DEP^® candidate, AZD0466, also set to enter the clinic later this year.

The DEP^® irinotecan trial will be conducted at multiple leading UK cancer centres including The Christie, The Royal Marsden and Newcastle Freeman Hospital as the initial trial sites. Additional sites in the UK and Australia will open and commence recruitment as the trial progresses and for the phase 2 part of the trial. Approximately 40-45 patients will be enrolled across the combined phase 1/2 trial.

Irinotecan, a widely used cancer drug marketed by Pfizer as Camptosar^® or Campto^®, is used alone or in combination with other drugs for the treatment of colorectal cancer (CRC). Despite US FDA “Black Box” warnings for both neutropenia and severe diarrhoea, Camptosar^® achieved peak annual sales of US$1.1 billion. The clinical use of irinotecan is limited by these toxicities.

DEP^® irinotecan is a novel, patented nanoparticle formulation of SN-38, the active metabolite of irinotecan, delivered using Starpharma’s proprietary DEP^® technology. DEP^® irinotecan has shown a number of benefits compared to the original form of irinotecan, including significant improvements in anti-cancer efficacy and improved survival in multiple human cancer models.

CRC is one of the most common cancers in the world, affecting more than 1 million individuals annually, and is the fourth-leading cause of cancer-related death. The efficacy of Camptosar^® in the treatment of cancer is dependent on the conversion of irinotecan in the liver to the active metabolite, SN-38, and this process can be highly variable within and between patients. The variability can lead to difficulties in patient management and dosing.  

Starpharma’s phase 1/2 study for DEP^® irinotecan will enrol patients with advanced solid tumours, including CRC, and is an open-label study. In the phase 1 part of the study, DEP^® irinotecan will be administered once every three weeks at escalating doses to characterise the safety, tolerability and pharmacokinetic (PK) profile of DEP^® irinotecan and to establish the RP2D. In the phase 2 part of the study, patients will be enrolled at the RP2D to generate information on the anti-tumour efficacy of DEP^® irinotecan in specific tumour types while further characterising the safety, tolerability and pharmacokinetics of the product.

The adaptive trial design employed will enable Starpharma to move seamlessly from phase 1 to phase 2 and to explore efficacy as early as possible. As the trial progresses, decisions will be made as to which tumour types to focus on, and the tumour types need not necessarily be limited to current indications approved for irinotecan. Already, DEP^® irinotecan has demonstrated exciting preclinical results in both colorectal and pancreatic cancer. Combination therapy regimens with DEP^® irinotecan may also be investigated.

Dr Jackie Fairley, Starpharma CEO, commented: “We are delighted to be advancing DEP^® irinotecan into the clinic. This is the third internal DEP^® product developed using Starpharma’s delivery platform to commence human trials. There are currently limited options available for colorectal cancer patients who do not respond to conventional therapy, and clinicians are keen to get this trial underway.”

“In addition to our three internal DEP^® products, we are also looking forward to  AstraZeneca’s first DEP^® product, AZD0466, commencing clinical trials later this year. The growing DEP^® clinical portfolio illustrates the optionality and commercial value created by Starpharma’s DEP^® platform,” concluded Dr Fairley.

Additional background:

DEP^® irinotecan has already been extensively investigated in preclinical human colon and pancreatic cancer models:

• DEP^® irinotecan showed significant efficacy and survival benefits over leading colorectal cancer drugs, irinotecan (Camptosar^®) and cetuximab (Erbitux^®), in the irinotecan-refractory, HT-29 human colon cancer model – announced on 24 May 2019.
• DEP^® irinotecan also showed impressive efficacy and survival benefits over standard irinotecan in combination with 5-FU in a human pancreatic cancer model – announced on 5 September 2018.

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