Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Single or multiple Intratumoural treatment of tigilanol tiglate at escalating doses of 0.6 mg/m2, 1.2 mg/m2 and 2.4 mg/m2 given every 28 days (+1 to 14days) in combination with three weekly 200 mg intravenous doses of pembrolizumab.

Single or multiple Intratumoural treatment of tigilanol tiglate at escalating doses of 0.6 mg/m2, 1.2 mg/m2 and 2.4 mg/m2.

Tigilanol tiglate is a novel, short-chain diterpene ester in early clinical development for local treatment of a wide range of solid tumours.

tigilanol tiglate

Three weekly 200 mg intravenous pembrolizumab treatment.

Pembrolizumab is a systemic anti-programmed cell death receptor 1 (PD 1) immunotherapy.

pembrolizumab

Prof. Georgina Long, BSc PhD MBBS FRACP FAHMS

Dr Megan Lyle, BMed FRACP

Dr Melvin Chin

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.

Intratumoural treatment with tigilanol tiglate combined with systemic anti-programmed cell death receptor 1 (PD 1) immunotherapy may enhance anti-tumour immune responses and improve outcomes for patients with melanoma.

Primary Objectives:

1. To determine the maximum tolerated dose (MTD) or maximum feasible dose (MFD) level of a single intratumoural treatment of tigilanol tiglate (Tx1) administered in combination with pembrolizumab.

2. To assess the safety and tolerability of: i) A single treatment (Tx1) of intratumoural tigilanol tiglate at escalating dose levels (dose-escalation) administered in combination with intravenous (IV) pembrolizumab (200 mg); and ii) Repeat treatments of intratumoural tigilanol tiglate (maximum of 3 treatments) administered in combination with IV pembrolizumab (200 mg, Q3W). Repeat treatment(s) of intratumoural tigilanol tiglate to be administered at the same dose level at Tx1 as follows:

1. If the initially injected tumour(s) are not fully ablated, then intratumoural tigilanol tiglate Tx2 +/- Tx3 may be re-administered to the same tumour(s).
2. If the initially injected tumour(s) are fully ablated and additional pre-identified tumours can be treated, then intratumoural tigilanol tiglate, Tx2 +/- Tx3 may also be administered to those tumours.

Note: Tumours identified at Screening that are designated as "not to be injected" tumours (i.e. non-injected tumours for observation) cannot be treated at Tx1, Tx2 or Tx3.

Secondary Objectives:

1. To evaluate tumour response according to RECIST 1.1 criteria, including loco-regional control of injected tumour(s) and non-injected tumour(s), and survival in patients treated in this study.
2. To assess the safety and tolerability of ongoing treatment with pembrolizumab up to a total of 35 cycles (Q3W), including the combination with up to 3 treatments of intratumoural tigilanol tiglate (Q3W).

Exploratory Objectives:

1. To evaluate the tumour response of tumours following treatment with intratumoural injection with tigilanol tiglate in combination with pembrolizumab

A Trial of Tigilanol Tiglate in Combination With Pembrolizumab in Stage IIIB to IV M1c-melanoma

A Phase Ib/IIa, Dose-escalation Study to Evaluate the Safety, Tolerability, and Preliminary Effectiveness of Intratumoural Tigilanol Tiglate in Combination With Intravenous Pembrolizumab in Adults With Stage IIIb to IV M1c-melanoma

To determine the dose level of intratumoural tigilanol tiglate when administered in combination with pembrolizumab (200 mg IV) at which there is no dose-limiting toxicity (DLT) recorded.

To determine the incidence of Treatment Emergent Adverse Events (TEAEs) including all grades of TEAEs and abnormal laboratory finding AEs

To assess the Objective Response Rate (ORR) includes partial response (PR) and complete response (CR) of injected tumours as well as non-injected tumours.

To assess the Best Overall Response (BOR) of injected as well as non-injected tumours.

To assess the Durable Response Rate (DRR) of injected tumours.

To assess the Duration of Response (DoR) of injected tumours

To assess the Progression Free Survival (PFS). Defined as the length of time during and after treatment that a patient lives without disease progression.

All Grade ≥ 3 TEAEs, serious (including fatal) AEs (SAEs), and TEAEs defined as events of interest by the Investigator.

Grading will be as per 'Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, 2017'. The CTCAE scale is measured from Grade 1 (mild) to Grade 5 (death).

Merck Sharp & Dohme LLC

QBiotics Group Limited

Single or multiple Intratumoural treatment of tigilanol tiglate at 3.6mg/m2 given at a minimum of 28-day intervals.

Single or multiple Intratumoural treatments of tigilanol tiglate up to a fixed dose level of 3.6mg/m2.

Tigilanol tiglate is a novel, short-chain diterpene ester in early clinical development for local treatment of a wide range of solid tumours.

A/Prof. Robyn Saw, MBBS FRACS MS

A/Professor Victoria Atkinson

A phase IIb, multicentre, open label study to evaluate the effectiveness, safety, and tolerability of intratumoural tigilanol tiglate in adult participants with Stage IIIB to IV M1c melanoma

Primary Objective

1. To evaluate the tumour responses of both injected and non injected tumours following treatment with intratumoural injections of tigilanol tiglate into one or more tumours (according to RECIST v1.1); and
2. To assess the tumour ablation rate following treatments with intratumoural injections of tigilanol tiglate.

Secondary Objectives

1. To assess the tumour recurrence rate at injected tumour site(s);
2. To assess the safety and tolerability of intratumoural injections of tigilanol tiglate;
3. To assess the degree of wound healing at injection sites; and
4. To evaluate disease control by looking at Progression Free Survival (PFS) in melanoma participants receiving tigilanol tiglate injections over 36 months.

Exploratory Objectives

1. To evaluate Overall Survival (OS) in melanoma participants receiving tigilanol tiglate injections over 36 months;
2. To assess the tumour microenvironment by looking at the degree of immune cell infiltration in non-injected tumours; and
3. To assess the Quality of Life (QoL) in melanoma participants receiving tigilanol tiglate injections.

A Trial of Intratumoural Tigilanol Tiglate in Adult Participants With Stage IIIB to IV M1c Melanoma

A Phase IIb, Multicentre, Open Label Study to Evaluate the Effectiveness, Safety and Tolerability of Intratumoural Tigilanol Tiglate in Adult Participants With Stage IIIB to IV M1c Melanoma

- To evaluate Overall Survival (OS) in melanoma participants receiving tigilanol tiglate injections

- To assess the tumour microenvironment by looking at the degree of immune cell infiltration in non-injected tumours

QoL assessment using the Functional Assessment of Cancer Therapy - Melanoma (FACT-M) questionnaire at screening and at 6-monthly intervals until the end of study.

- To evaluate the tumour responses of both injected and non injected tumours following treatment with intratumoural injections of tigilanol tiglate into one or more tumours (long term tumour response according to RECIST v1.1 criteria).

- To assess the tumour ablation rate following treatment(s) with intratumoural injections of tigilanol tiglate.

- To assess the tumour recurrence rate at injected tumour site(s)

Total number of Adverse Events and Serious Adverse Events. Number of Adverse Events and Serious Adverse Events deemed related to tigilanol tiglate.

- To assess the degree of wound healing at injection site(s) using a specifically designed Injection Site Assessment Worksheet, observed at 14 and 28 days post treatment.

- To evaluate disease control by looking at Progression Free Survival (PFS) in melanoma participants receiving tigilanol tiglate injections over 36 months

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Trial of Tigilanol Tiglate in Combination With Pembrolizumab in Stage IIIB to IV M1c-melanoma	NCT04834973	Melanoma	tigilanol tigla... pembrolizumab	18 Years -	QBiotics Group Limited
A Trial of Intratumoural Tigilanol Tiglate in Adult Participants With Stage IIIB to IV M1c Melanoma	NCT05234437	Melanoma	tigilanol tigla...	18 Years -	QBiotics Group Limited

Spots Global Cancer Trial Database for intratumoural