A Clinical Study to Investigate the Efficacy of Tigilanol Tiglate Directly in Head and Neck Cancer

Inclusion Criteria:

1. Are willing and able to provide written informed consent for the study prior to anyprotocol-specific procedures and to comply with all local and study requirements.

2. Are ≥ 18 years of age on the day of providing informed consent.

3. Have a histologically confirmed diagnosis of a solid head and neck malignancy andhave either recurrent disease and/or metastatic disease, or have failed on at leastone line of systemic therapy. Tumour types can include: HNSCC, sino-nasal cancers,salivary gland cancers, and peri-stomal laryngeal carcinomas with pre-existingtracheostomy.

4. Have disease that is amenable to intratumoural injection either by palpation orunder ultrasound guided injection. Lymph nodes with metastatic disease from thepatient's head and neck cancer can be selected for treatment. Note: Measurabledisease as per RECIST v1.1. is not mandatory.

5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

6. Have life expectancy of more than 12 weeks.

7. Female participants who are Women of Child-Bearing Potential (WOCBP) must have anegative serum pregnancy test at Screening (within 14 days of the first study drugadministration), must be willing to use a highly effective contraception from dateof consent, throughout the study period and up to 30 days after the last study drugadministration, and must not be breastfeeding.

8. Male participants with a potentially fertile female partner are eligible if theyhave had a vasectomy or are willing to use adequate contraception from prior tocommencement of study drug administration, throughout the study period and up to 30days after the last study drug administration, and must not donate sperm throughoutthe study period and up to 30 days after the last study drug administration.

Exclusion Criteria:

1. Are planning to receive intratumoural treatment or radiotherapy to any of thetumours intended for injection within 28 days prior to Screening, or duringtreatment with tigilanol tiglate.

2. Have a tumour intended for injection that is immediately adjacent to, or withinfiltration into, any major artery or vein (e.g., if the tumour for injection islocated adjacent to the jugular vein).

3. Have a tumour intended for injection located in an area where post-injectionswelling could compromise the airway.

4. Have a tumour intended for injection that is a nasal tumour extending into theEthmoid sinus.

5. Have had any previous intervention (extensive surgery or radiation therapy) in thearea of a tumour intended for injection that is in proximity of the airway (suchthat tracking of the injected fluid may be unpredictable and could lead to airwayswelling). Patients with a permanent tracheostomy can be included.

6. Are receiving or have received other investigational agents or have used aninvestigational device without undergoing a 28-day (or 5 half-lives, whichever isshorter) wash-out period prior to their first treatment with tigilanol tiglate.These patients must have recovered from all AEs due to previous investigationaltherapies to ≤ Grade 1 at baseline.

7. Are receiving or have received systemic anticancer therapy, or therapeutic radiationtreatment, without undergoing a 28-day (or 5 half-lives, whichever is shorter)wash-out period prior to their first treatment with tigilanol tiglate. Thesepatients must have recovered from all AEs due to previous therapies to ≤ Grade 1 atbaseline.

8. Have had major surgery within 28 days of their first treatment with tigilanoltiglate or anticipate the need for major surgery during the study period. Minorsurgical procedures are permitted, but with sufficient time for wound healing.

9. Have known, current or history of active cerebral metastasis and/or carcinomatousmeningitis.

10. Have any bleeding diathesis or coagulopathy that would make intratumoural injectionor biopsy unsafe, or if they are on therapeutic warfarin therapy.

11. Have a history of allergic reactions or severe hypersensitivity (Grade ≥ 3)attributed to tigilanol tiglate or compounds of similar chemical or biologiccomposition to tigilanol tiglate, any of its excipients or other agents used in thestudy.

12. In the opinion of the treating Investigator, the patient is not an appropriatecandidate for the study for any reason (e.g., they have a known psychiatric orsubstance abuse disorder that would interfere with their ability to cooperate withthe requirements of the study).