A Trial of Tigilanol Tiglate in Combination With Pembrolizumab in Stage IIIB to IV M1c-melanoma
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|ClinicalTrials.gov Identifier: NCT04834973|
Recruitment Status : Recruiting
First Posted : April 8, 2021
Last Update Posted : March 23, 2022
|Condition or disease||Intervention/treatment||Phase|
|Melanoma||Drug: tigilanol tiglate Drug: pembrolizumab||Phase 1 Phase 2|
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.
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:
- 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).
- 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.
- 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.
- 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).
1. To evaluate the tumour response of tumours following treatment with intratumoural injection with tigilanol tiglate in combination with pembrolizumab
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Standard 3 + 3 Dose escalation study|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||May 7, 2021|
|Estimated Primary Completion Date :||July 2022|
|Estimated Study Completion Date :||September 2024|
Experimental: Single arm open label
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 in combination with three weekly 200 mg intravenous doses of pembrolizumab.
Drug: tigilanol tiglate
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.
Three weekly 200 mg intravenous pembrolizumab treatment.
Pembrolizumab is a systemic anti-programmed cell death receptor 1 (PD 1) immunotherapy.
Other Name: Keytruda
- Determine Dose Level [ Time Frame: 12 months ]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.
- Determine incidence of Treatment Emergent Adverse Events [ Time Frame: 12 months ]To determine the incidence of Treatment Emergent Adverse Events (TEAEs) including all grades of TEAEs and abnormal laboratory finding AEs
- Objective Response Rate (ORR) [ Time Frame: 24 months ]To assess the Objective Response Rate (ORR) includes partial response (PR) and complete response (CR) of injected tumours as well as non-injected tumours.
- Best Overall Response (BOR) [ Time Frame: 24 months ]To assess the Best Overall Response (BOR) of injected as well as non-injected tumours.
- Durable Response Rate (DRR) [ Time Frame: 24 months ]To assess the Durable Response Rate (DRR) of injected tumours.
- Duration of Response (DoR) [ Time Frame: 24 months ]To assess the Duration of Response (DoR) of injected tumours
- Progression Free Survival (PFS) [ Time Frame: 24 months ]To assess the Progression Free Survival (PFS). Defined as the length of time during and after treatment that a patient lives without disease progression.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04834973
|Contact: Head of Human Clinical Operationsfirstname.lastname@example.org|
|Australia, New South Wales|
|Melanoma Institute Australia||Recruiting|
|Wollstonecraft, New South Wales, Australia, 2065|
|Contact: Prof Georgina Long, BSc PhD MBBS FRACP|
|Cairns and Hinterland Hospital and Health Service||Not yet recruiting|
|Cairns, Queensland, Australia, 4870|
|Contact: Dr Megan Lyle, BMed FRACP|
|Principal Investigator:||Prof. Georgina Long, BSc PhD MBBS FRACP FAHMS||Melanoma Institute Australia|
|Principal Investigator:||Dr Megan Lyle, BMed FRACP||Cairns and Hinterland Hospital and Health Service|