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TERMINATEDPHASE1/PHASE2

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

NCT04834973•QBiotics Group Limited

View on ClinicalTrials.gov

Summary

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.

Detailed Description

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

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•A patient will be eligible for study participation if they meet ALL of the following criteria:
•1. Are willing and able to provide written informed consent for the study prior to any protocol-required procedures and to comply with all local and study requirements. (Note: If a patient is unable to provide written informed consent, a legally acceptable representative may provide consent on their behalf).
•2. Are an adult at least 18 years of age on the day of providing informed consent.
•3. Have a histologically confirmed diagnosis of melanoma that is Stage IIIB to IV M1c (AJCC 8th Ed.) for whom surgery is not recommended. Only patients previously exposed to a checkpoint inhibitor are eligible. Prior BRAF inhibitor therapy is allowed for BRAF V600+ patients.
•4. Have measurable disease per RECIST v1.1 including cutaneous or subcutaneous tumours, or regional lymph nodes consisting of ≥ 1 target tumour accessible and amenable to intratumoural injection and ≥ 1 target tumour designated as a non-injected tumour for observation that can be accurately measured by contrast enhanced CT or MRI as assessed by the Investigator's local site radiology.
•5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
•6. Have life expectancy of more than 12 weeks.
•7. Have adequate organ function as defined below. Specimens must be collected within 10 days prior to the start of study treatment.
•Haematological:
•Absolute neutrophil count (ANC) ≥ 1500/µL Platelets ≥ 100 000/µL Haemoglobin ≥ 9.0 g/dL OR ≥ 5.6 mmol/L1
+14 more criteria

Exclusion Criteria

•A patient will be excluded from study participation if ANY of the following criteria apply:
•1. Patients who are planning to receive intratumoural treatment or radiotherapy to any of the intended target tumours within 4 weeks prior to Screening, or during treatment with tigilanol tiglate or pembrolizumab, or who have received radiotherapy within 2 weeks of the start of study treatment. (Note: Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 4-week washout is permitted for palliative radiation \[≤4 weeks of radiotherapy\] to non-CNS disease).
•2. A tumour intended for injection that is immediately adjacent to, or with infiltration into, any major artery or vein.
•3. A tumour intended for injection located in an area where post-injection swelling could compromise the airway.
•4. Any previous intervention in the area of the intended injected tumour in proximity of the airway (such that tracking of the injected fluid may be unpredictable and could lead to airway swelling).
•5. A histologically confirmed diagnosis of uveal or mucosal melanoma as the only intended injected tumour.
•6. Have a positive urine pregnancy test within 72 hours prior to start of study treatment (Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required).
•7. Have received a live vaccine within 30 days prior to the start of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG) and typhoid vaccine. (Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines \[e.g., FluMist®\] are live attenuated vaccines and are not allowed).
•8. Are planning to receive concomitant other biologic therapy, hormonal therapy, other chemotherapy to treat their melanoma while on study treatment.
•9. Have received any of the following within 4 weeks prior to the start of study treatment; systemic anticancer therapy, including investigational agents, or has participated in a study of an investigational agent or has used an investigational device. (Note: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been at least 4 weeks after the last dose of the previous investigational agent). Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline patients with ≤ Grade 2 neuropathy may be eligible. (Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment). (Note: Patients who have received systemic anticancer therapy can be considered for inclusion provided a washout period of 4 weeks or 5 half-lives, whichever is shorter, has occurred).
+14 more criteria

Locations (2)

Melanoma Institute Australia

Wollstonecraft, New South Wales, Australia

Cairns and Hinterland Hospital and Health Service

Cairns, Queensland, Australia

Key Dates

Start Date

May 7, 2021

Primary Completion Date

July 12, 2022

Completion Date

July 12, 2022

Last Updated

April 18, 2023

Enrollment

ACTUAL participants

Conditions

Melanoma

Interventions

tigilanol tiglate

DRUG

pembrolizumab

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: April 18, 2023Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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

Inclusion Criteria

Exclusion Criteria

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