Human

Tigilanol tiglate exhibits early promise for treating solid tumours in humans

Tigilanol tiglate is a novel small molecule under clinical development as an intratumoural treatment for solid tumours.  Human and veterinary clinical trials have demonstrated that the drug has the ability to treat a range of solid tumour types.  We are currently focusing on unresectable tumours and tumours that are in difficult to access areas.  However, tigilanol tiglate may have a much broader range of (i) potential indications and (ii) specialised application e.g. for patients that cannot undergo surgery due to fraility, are immunocompromised or in palliative care. Tigilanol tiglate is being developed as a monotherapy (i.e. a stand alone treatment), as well as in combination with immune checkpoint inhibitor drugs. 

As a monotherapy, our initial focus in humans is on externally located tumours in the indications of Head and Neck Squamous Cell Carcinoma (HNSCC), Melanoma and Soft Tissue Sarcoma.  However, there is also the potential to treat a broader range of solid tumours that are accessible for injection via palpitation, or guided by imaging, such as prostate cancer.

There is also preliminary evidence that tigilanol tiglate may have an anenestic effect (i.e. causes responses in non-injected tumours distant from the injected tumour) and we are currently exploring this aspect in more detail.

Clinical programmes

Tigilanol tiglate was well-tolerated and showed efficacy signals in a first-in-human clinical safety trial

A Phase Ia/IIb dose-escalation safety trial in 22 patients with refractory skin and subcutaneous solid tumours has been completed. The results show that tigilanol tiglate is generally well tolerated with a maximum tolerated dose (MTD) not reached. Clinically-relevant tumour responses were observed across all 9 solid tumour types tested, including squamous cell carcinoma, melanoma, basal cell carcinoma, breast adenocarcinoma, atypical fibroxanthoma, myxoid fibrosarcoma, colorectal adenocarcinoma, adenoid cystic carcinoma and angiosarcoma1.

In addition, 6 of the 22 patients (27%) experienced a treatment response, with 4 of the 6 patients (18%) achieving a Complete Response (full tumour destruction) in the injected tumour. Two of the patients with melanoma also had  anenestic responses (tumour shrinkage or destruction) in non-injected tumours.

These results are supported by a strong body of preclinical evidence obtained in from studies of spontaneous tumours in client-owned dogs.

Following these positive results, QBiotics is progressing clinical trials in patients with head and neck squamous cell carcinoma, melanoma and soft tissue sarcoma.

Four value-building trials across a range of solid tumours

summary table

Market need

Disease Incidence and Prevalence

Head and neck cancer is the 7th most common cancer globally, with ~1.46 million new cases reported in 2018, and ~962,000 deaths2. It is associated with tobacco and alcohol use and its incidence is increasing due to human papillomavirus infection.

For melanoma, there were ~287,000 new cases reported globally in 2018, and ~61,000 deaths. The incidence of new cases of melanoma diagnosed each year is rising at 5% per year3.

Head & neck cancer

~1.46 million new cases reported in 2018

Melanoma

~287,000 new cases reported in 2018

Solid tumours

~18.1 million newly diagnosed cases

Monotherapy

Surgery is the standard of care for the treatment of solid tumours4.  However in many cases, the tumours are unresectable (unable to be removed by surgery), surgery can be disfiguring, or patients may be too unwell for surgery. Surgery requires not only removal of the tumour mass, but also a large margin of healthy tissue, and often the tumours are located in difficult to access areas. These tumours do not always respond to other treatments such as chemotherapy, radiotherapy and immunotherapy. As a result, there is a significant unmet need for new treatments that can remove unresectable tumours, especially in the head and neck region to preserve a person’s appearance, as well as critical functions such as sight, hearing, speech and swallowing5.

Combination with immune checkpoint inhibitors

The immune checkpoint inhibitors (ICIs) such as Keytruda® (pembrolizumab) and Opdivo® (nivolumab) are leading the market for systemic treatment of solid tumour cancers6.  Although these drugs have achieved considerable success, there remains opportunities for improvement in the response rates and safety aspects of the ICIs7. Therefore, the pharmaceutical companies are exploring the potential in combining the ICI drugs with other treatments, such as intratumoural treatment, to increase response rates and overall patient wellfare7.

Combination partner products that work via a different mode of action to ICIs are likely to improve efficacy without increasing toxicity.

Tigilanol tiglate is a new combination partner product. It has been shown to synergise with the ICI drugs (anti-CTLA-4 and/or anti-PD-1 mAbs) to destroy injected tumours and shrink non-injected tumours in a B16-F10 metastatic mouse model (an ICI refractory model)8.

QBiotics has entered into a clinical collaboration with MSD (tradename of Merck & Co. Inc, Kenilworth, NJ, USA), to evaluate the use of tigilanol tiglate, in combination with the ICI pharmaceutical Keytruda® (pembrolizumab) in patients with unresectable melanoma in a Phase Ib/IIa clinical trial.


  1. Panizza et al., 2019.
  2. Globocan 2018. Estimated age-standardized incidence rates (World) in 2018, lip, oral cavity, salivary glands, oropharynx, nasopharynx, hypopharynx, both sexes, all ages. Includes oesophagus and larynx.American Society of Clinical Oncology.
  3. Koh et al., 2019. Ibid Globocan, 2018
  4. American Society of Clinical Oncology.
  5. NCCN Guidelines Version 1. 2019. Head and Neck Cancers; Koh et al., 2019. Head and neck squamous cell carcinoma survivorship care. AJGP 48:846-848.
  6. Research and Markets (2020). Immune Checkpoint Inhibitors Markets, 2011-2019 & 2020-2025.
  7. Fares et al., 2019. Mechanisms of resistance to immune checkpoint blockade: Why does checkpoint inhibitor immunotherapy not work for all patients? DOI: 10.1200/EDBK_240837 American Society of Clinical Oncology Educational Book 39 (May 17, 2019) 147-164.
  8. QBiotics. Data on File, 2019.