QBiotics Group Limited, a life sciences company developing novel small molecule anticancer and wound healing pharmaceuticals, is pleased to announce that it has dosed the first patient in the Phase Ib/IIa clinical trial of the company's lead oncology molecule, tigilanol tiglate in combination with MSD's immune checkpoint inhibitor KEYTRUDA? (pembrolizumab) for patients with unresectable melanoma, the deadliest form of skin cancer. 

The QB46C-H06 multi-centre, open label study will enrol approximately 22 patients with Stage IIIB to IV M1c-melanoma across a number of Australian sites over 24 months. The study will test up to three intratumoural doses of tigilanol tiglate at three escalating dose levels, administered 3 weeks apart in combination with intravenous pembrolizumab administered every 3 weeks for up to 24 months. The study will evaluate the safety, optimal dose and tumour response of the tigilanol tiglate and pembrolizumab combination in patients with late-stage unresectable melanoma, who have been previously exposed to immune checkpoint inhibitors.

Dr Victoria Gordon, Managing Director and CEO of QBiotics, said "We are very pleased to be collaborating with MSD in the fight against melanoma, a deadly form of skin cancer prevalent worldwide, but especially so here in Australia.

Dr Gordon continued "Patients with unresectable melanoma who have received prior checkpoint inhibitors currently have limited effective treatment options. We hope to see that when combined, tigilanol tiglate and KEYTRUDA? may produce additive anti-tumour immune responses, improving outcomes for patients."

Over the last decade, the global cases of melanoma have increased by nearly 50 percent, with more than 320,000 people diagnosed annually. This translates to approximately 60,000 melanoma-related deaths per year[1]. Australia has the highest melanoma rates in the world, with one person diagnosed every 30 minutes, and an estimated 1,300 deaths each year.[2] 

Tigilanol tiglate is a plant-derived small molecule, administered by injection directly into a solid tumour. Injected tumours are rapidly destroyed by tumour cell necrosis, vascular disruption, and immune-mediated mechanisms.[3] Pembrolizumab is a systemic immune checkpoint inhibitor, which reactivates the immune system by blocking the activity of PD-1, an immune checkpoint protein that prevents T cells from recognising and killing cancer cells.[4] 

"The commencement of this trial with our first patient dosed is a significant milestone for QBiotics and is underpinned by positive outcomes from our Phase I QBC46-H01 Phase I study using tigilanol tiglate as a monotherapy in 22 patients with a broad range of refractory solid tumours.  In this Phase I study a single injection of tigilanol tiglate showed an injected tumour response rate of 60% (CR of 20%, PR of 28%, SD of 12%).[5] Non-injected (abscopal) responses in distal tumours were observed in two patients with melanoma[6]," said Dr Gordon. 

ABOUT TRIAL NCT04834973

A Phase Ib/IIa, multicentre, open label, dose-escalation study to evaluate the safety, tolerability, and preliminary effectiveness of intratumoural tigilanol tiglate in combination with intravenous pembrolizumab in adult patients with unresectable, Stage IIIB to IV M1c melanoma.

The primary objectives are 1.  To determine the maximum tolerated dose (MTD) or maximum feasible dose (MFD) level of a single intratumoural injection of tigilanol tiglate administered in combination with intravenous pembrolizumab (200 mg), and 2. To assess the safety and tolerability of i) A single injection of tigilanol tiglate at escalating dose levels (dose-escalation) administered in combination with pembrolizumab; and ii) Repeat injections of tigilanol tiglate (maximum of 3) administered in combination with pembrolizumab.  Secondary objectives include tumour responses according to RECIST 1.1 criteria, including loco-regional control of injected tumour(s) and non-injected tumour(s), and survival in patients.

ABOUT QBIOTICS

QBiotics is a public unlisted Australian life sciences company which discovers, develops and commercialises novel anticancer and wound healing pharmaceuticals for human and veterinary markets. Its lead molecule, tigilanol tiglate, is a small molecule anticancer pharmaceutical targeting a range of solid tumours across multiple species.  QBiotics' business model is to develop products that have application in both veterinary and human markets. Success in the veterinary programs validates QBiotics technology and de-risks human development, while generating early, non-diluting revenues.

ABOUT TIGILANOL TIGLATE

Tigilanol tiglate is a small molecule being developed as an intratumoural treatment for solid tumours. It has a multimodal action that involves injected tumour responses as well as systemic responses in non-injected tumours. Complete destruction of the injected tumour is mediated via tumour vascular disruption, death of tumour cells by oncosis and immune-mediated mechanisms.3 Following tumour destruction, rapid wound healing has been shown to ensue.

A veterinary version of tigilanol tiglate (STELFONTA?) is approved to treat canine mast cell tumours. STELFONTA? is marketed in Europe, the United Kingdom and USA by QBiotics partner Virbac, a global animal health company.  STELFONTA? is also under review by the Australian Pesticides and Veterinary Medicines Authority. In a pivotal US study, a single injection of STELFONTA? induced a 75% complete response, and an 88% complete response with two injections. There was no tumour recurrence in 89% of evaluable cases 12 months post-treatment.[7]

[1] Globocan, (2020) Melanoma of Skin, https://gco.iarc.fr/today/data/factsheets/cancers/16-Melanoma-of-skin-fact-sheet.pdf

[2] Global Coalition for Melanoma Patient Advocacy, (2020) Melanoma Skin Cancer Report, https://melanomapatients.org.au/wp-content/uploads/2020/04/2020-campaign-report-GC-version-MPA_1.pdf

[3] Boyle et al., (2014) Intra-tumoural injection of the novel PKC activator EBC-46 rapidly ablates tumours in mouse models. PLoS One 9:e1068887.

[4] Hamid et al., (2019) Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Annals of Oncology 30: 582–588.   

[5] CR, complete response; PR, partial response; SD, stable disease.   

[6] Panizza et al., (2019) Phase I dose-escalation study to determine the safety, tolerability, preliminary efficacy and pharmacokinetics of an intra tumoural injection of tigilanol tiglate (EBC-46). EBioMedicine 50: 433-441.

[7] De Ridder et al., (2020). Randomized controlled clinical study evaluating the efficacy and safety of intratumoral treatment of canine mast cell tumors with tigilanol tiglate. J. Vet. Inter. Med. 1-15.