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

NCT04834973 | Terminated Phase 1 DMC

• 3 other identifiers: QB46C-H06KN-B16U1111-1258-4085
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Melanoma

Keywords

Melanoma; Intratumoural; Tigilanol Tiglate; Pembrolizumab; Keytruda; Epoxytigilane

Outcome Measures

Primary Outcomes (2)

• Determine Dose Level

  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.

  12 months

• Determine incidence of Treatment Emergent Adverse Events

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

  12 months

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  24 months

• Best Overall Response (BOR)

  24 months

• Durable Response Rate (DRR)

  24 months

• Duration of Response (DoR)

  24 months

• Progression Free Survival (PFS)

  24 months

Study Arms (1)

Single arm open label

EXPERIMENTAL

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.

Drug: tigilanol tiglate; Drug: pembrolizumab

Interventions

tigilanol tiglate DRUG

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.

Also known as: EBC-46

Single arm open label

pembrolizumab DRUG

Three weekly 200 mg intravenous pembrolizumab treatment. Pembrolizumab is a systemic anti-programmed cell death receptor 1 (PD 1) immunotherapy.

Also known as: Keytruda

Single arm open label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A patient will be eligible for study participation if they meet ALL of the following criteria:
• 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).
• Are an adult at least 18 years of age on the day of providing informed consent.
• 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.
• 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.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have life expectancy of more than 12 weeks.
• 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
• Renal
• Creatinine OR Measured or calculated2 creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 × ULN OR
• ≥ 30 mL/min for patient with creatinine levels \> 1.5 × institutional ULN
• Hepatic
• Total bilirubin: ≤ 1.5 × ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels \> 1.5 × ULN

You may not qualify if:

• A patient will be excluded from study participation if ANY of the following criteria apply:
• 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).
• A tumour intended for injection that is immediately adjacent to, or with infiltration into, any major artery or vein.
• A tumour intended for injection located in an area where post-injection swelling could compromise the airway.
• 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).
• A histologically confirmed diagnosis of uveal or mucosal melanoma as the only intended injected tumour.
• 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).
• 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).
• Are planning to receive concomitant other biologic therapy, hormonal therapy, other chemotherapy to treat their melanoma while on study treatment.
• Have known, current or history of central nervous system metastases, active cerebral metastasis and/or carcinomatous meningitis.
• Have any bleeding diathesis or coagulopathy, or are taking warfarin, that would make intratumoural injection or biopsy unsafe.
• Clinically significant acute or unstable cardiovascular, cerebrovascular disorders.
• Patients with significant peripheral vascular disease whose accessible tumours intended for injection are located in their extremities.
• Have prior allogeneic tissue/solid organ transplant.
• Have a history of allergic reactions or severe hypersensitivity (Grade ≥ 3) attributed to tigilanol tiglate or pembrolizumab, compounds of similar chemical or biologic composition to tigilanol tiglate or pembrolizumab, any of their excipients or other agents used in the study, or have experienced unacceptable toxicity to a checkpoint inhibitor.

Sponsors & Collaborators

• QBiotics Group Limited: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

Location

Cairns and Hinterland Hospital and Health Service

Cairns, Queensland, 4870, Australia

Location

MeSH Terms

Conditions

Melanoma

Interventions

EBC-46; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• Dr Melvin Chin

  Prince of Wales Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Standard 3 + 3 Dose escalation study

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: April 8, 2021
• Study Start: May 7, 2021
• Primary Completion: July 12, 2022
• Study Completion: July 12, 2022
• Last Updated: April 18, 2023

Record last verified: 2023-04

Locations

AU (2)