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

A Phase II, open label, single arm study to assess the efficacy of intratumoural tigilanol tiglate in various head and neck solid malignancies.

Primary Objective

1. To evaluate tumour ablation following treatment(s) with intratumoural injections of tigilanol tiglate.

Secondary Objectives

1. To assess the safety and tolerability of intratumoural injections with tigilanol tiglate.
2. To evaluate disease control by assessing time to local disease recurrence from last treatment.
3. To evaluate the tumour recurrence rate at injected tumour sites.
4. To evaluate survival by assessing Progression Free Survival (PFS).

Exploratory Objectives

1. To assess the impact on Quality of Life (QoL).
2. To assess the degree of wound healing after each treatment.
3. To assess the tumour response in injected and non-injected tumours, based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.
4. To assess the tumour response according to intratumoural Response Evaluation Criteria in Solid Tumours (itRECIST).
5. To assess changes in tumour biomarkers.
6. To assess the tumour microenvironment.

Eligibility Criteria:
Inclusion Criteria:

1. Are willing and able to provide written informed consent for the study prior to any protocol-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 and have either recurrent disease and/or metastatic disease, or have failed on at least one line of systemic therapy. Tumour types can include: HNSCC, sino-nasal cancers, salivary gland cancers, and peri-stomal laryngeal carcinomas with pre-existing tracheostomy.
4. Have disease that is amenable to intratumoural injection either by palpation or under ultrasound guided injection. Lymph nodes with metastatic disease from the patient's head and neck cancer can be selected for treatment. Note: Measurable disease 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 a negative serum pregnancy test at Screening (within 14 days of the first study drug administration), must be willing to use a highly effective contraception from date of consent, throughout the study period and up to 30 days after the last study drug administration, and must not be breastfeeding.
8. Male participants with a potentially fertile female partner are eligible if they have had a vasectomy or are willing to use adequate contraception from prior to commencement of study drug administration, throughout the study period and up to 30 days after the last study drug administration, and must not donate sperm throughout the 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 the tumours intended for injection within 28 days prior to Screening, or during treatment with tigilanol tiglate.
2. Have a tumour intended for injection that is immediately adjacent to, or with infiltration into, any major artery or vein (e.g., if the tumour for injection is located adjacent to the jugular vein).
3. Have a tumour intended for injection located in an area where post-injection swelling could compromise the airway.
4. Have a tumour intended for injection that is a nasal tumour extending into the Ethmoid sinus.
5. Have had any previous intervention (extensive surgery or radiation therapy) in the area of a tumour intended for injection that is in proximity of the airway (such that tracking of the injected fluid may be unpredictable and could lead to airway swelling). Patients with a permanent tracheostomy can be included.
6. Are receiving or have received other investigational agents or have used an investigational device without undergoing a 28-day (or 5 half-lives, whichever is shorter) wash-out period prior to their first treatment with tigilanol tiglate. These patients must have recovered from all AEs due to previous investigational therapies to ≤ Grade 1 at baseline.
7. Are receiving or have received systemic anticancer therapy, or therapeutic radiation treatment, without undergoing a 28-day (or 5 half-lives, whichever is shorter) wash-out period prior to their first treatment with tigilanol tiglate. These patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 at baseline.
8. Have had major surgery within 28 days of their first treatment with tigilanol tiglate or anticipate the need for major surgery during the study period. Minor surgical procedures are permitted, but with sufficient time for wound healing.
9. Have known, current or history of active cerebral metastasis and/or carcinomatous meningitis.
10. Have any bleeding diathesis or coagulopathy that would make intratumoural injection or 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 biologic composition to tigilanol tiglate, any of its excipients or other agents used in the study.
12. In the opinion of the treating Investigator, the patient is not an appropriate candidate for the study for any reason (e.g., they have a known psychiatric or substance abuse disorder that would interfere with their ability to cooperate with the requirements of the study).