Safety and Efficacy of ASN-002 Combined With a Hedgehog Pathway Inhibitor

NCT04416516 | Completed Phase 2

• 1 other identifier: ASN-002-003
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 7

Brief Summary

The primary objectives are to:

1. 1.Evaluate the safety and tolerability of intralesional ASN-002 when administered in combination with oral vismodegib in patients with Basal Cell Carcinomas (BCC)s;
2. 2.Evaluate the efficacy of intralesional ASN-002 in target tumours when administered in combination with oral vismodegib in patients with BCCs.

Conditions

Basal Cell Carcinoma; Basal Cell Nevus Syndrome

Keywords

high frequency basal cell carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of ASN-002 related Adverse Events in patients with previously untreated nBCC

  Incidence of Adverse Adverse events will be monitored

  Participants will be followed up to 6 months

• Microscopic clearance of the injected Target basal cell carcinoma.

  Histological clearance (HC) will be defined as the absence of detectable evidence of BCC tumor cell nests in serial histological samples as determined by central pathology review.

  Microscopic examinations of sample collected at weeks 25-33 after the first dose.

Secondary Outcomes (1)

• Microscopic clearance of the injected Non-Target basal cell carcinoma.

  Microscopic examinations of sample collected at weeks 25-33 after the first dose.

Study Arms (3)

Arm 1, Patients with 1 Tumour

EXPERIMENTAL

Participants with 1 Target Tumour will receive 3 x ASN-002 1.0x10(11) Injections \+ VISMODEGIB (150 mg) daily for 4 weeks.

Biological: ASN-002

Arm 2, Patients with 3 or more Tumours

EXPERIMENTAL

Participants with 3 or more Target Tumours will receive 3 x ASN-002 1.0x10(11) Injections (per tumour) + VISMODEGIB (150 mg) daily for 4 weeks.

Biological: ASN-002

Arm 6 Patients with 3 or more Tumours

EXPERIMENTAL

Participants with 3 or more Target Tumours will receive 3 x ASN-002 1.5x10(11) Injections (per tumour) + VISMODEGIB (150 mg) daily for 4 weeks

Biological: ASN-002

Interventions

ASN-002 BIOLOGICAL

ASN-002 has been designed for clinical applications, especially for intratumoral administration in the treatment of various cancers. This rAd vector delivers the gene of interest, in the case of ASN-002 the human IFNγ gene, into target cells. The rAd vector in ASN-002 is replication deficient and although it infects cells, it is not able to replicate in the tumor or in normal human cells. The infected cells are able to transcribe and translate the IFNγ DNA leading to a sustained local concentration of IFNγ in the tumor mass that is designed to avoid high levels of systemic IFNγ that may be lead to unacceptable toxicity.

Arm 1, Patients with 1 Tumour; Arm 2, Patients with 3 or more Tumours; Arm 6 Patients with 3 or more Tumours

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed previously untreated, BCC (nodular and superficial), 5-20 mm in maximum diameter, per the selection criteria for study BCC tumours. A punch biopsy (refer to study procedure manual for biopsy size selection) from the thickest part of all the target tumours is required for histological confirmation of BCC and to exclude BCC non-eligible subtypes.
• Note: If a patient has mix of nodular and superficial BCC tumours, at least one target tumour should be a nodular BCC.
• Removal of \< 25% of the area of each biopsied tumour by initial biopsy performed 1-12 weeks before Day 1. If the initial biopsy was performed \>8 weeks prior to screening, the investigator may re-biopsy the tumour, provided not \> 25% of the area of the original tumour is removed. Non-study tumours may be resected or treated at the discretion of the Investigator prior to study entry or if they develop during the study.
• Hedgehog pathway inhibitor treatment naïve.
• Acceptable general health as determined by the investigator, i.e. no serious or active medical or psychiatric illness or recreational or therapeutic drug or alcohol use that, in the opinion of the Investigator, would interfere with treatment, assessment or compliance with the protocol, ability to provide informed consent, or patient safety.
• years of age or older.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
• Screening laboratory values as follows:
• Neutrophil count \> 1500/mm3
• Haemoglobin \> 9 g/dL
• Platelet count \>100,000/mm3
• Prothrombin INR \< 1.5
• Total bilirubin \< 1.5 X upper limit of normal (ULN), except in the case of known Gilbert's syndrome
• Aspartate transaminase (AST), alanine transaminase (ALT) or alkaline phosphatase (ALP) \< 2X ULN
• Creatinine \< 1.5 X upper limit of normal (ULN)

You may not qualify if:

• Known or suspected metastatic disease or other active, invasive malignancy.
• Female patients of childbearing potential who are lactating or pregnant (negative serum pregnancy test needed prior to dosing).
• Clinically active or uncontrolled skin disease or tattoos that would interfere with evaluation of the area surrounding the target tumour (e.g. eczema, unstable psoriasis, xeroderma pigmentosa).
• Known history of sensitivity to any of the ingredients in ASN-002 and any Hh pathway inhibitors.
• Has received or is expected to receive treatment with psoralen plus UVA or UVB therapy within 6 months of the Screening visit.
• Any prior systemic anti-tumour therapy or local treatment for target tumours prior to first dose.
• History of immunological disorder, severe allergic reaction, moderate or severe asthma or known history of anaphylaxis or any other serious adverse reactions to any medication.
• Any experimental or investigational agents within one month of first ASN-002 injection.
• Any prior exposure to TG1041, TG1042 (ASN-002), any other adenoviral-based experimental agent, or any form of gene therapy within 6 months of first dose of vismodegib in the study.
• Any prior exposure to vismodegib or any other Hh inhibitor within 6 months of first dose in the study.
• Current therapy with any medications recognized to cause rhabdomyolysis or a prior history of rhabdomyolysis.

Sponsors & Collaborators

• Ascend Biopharmaceuticals Ltd: lead

Study Sites (7)

Central Brisbane Dermatology

Brisbane, Queensland, 4000, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Veracity Clinical Research

Brisbane, Queensland, 4102, Australia

Location

Sunshine Coast University Hospital

Sunshine Coast, Queensland, Australia

Location

Sinclair Dermatology

Melbourne, Victoria, 3000, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Burswood Dermatology

Perth, Western Australia, 6100, Australia

Location

MeSH Terms

Conditions

Carcinoma, Basal Cell; Basal Cell Nevus Syndrome

Interventions

gusacitinib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell; Odontogenic Cysts; Jaw Cysts; Bone Cysts; Cysts; Neoplastic Syndromes, Hereditary; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Jaw Diseases; Stomatognathic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Clement Leong, Ph.D

  Ascend Biopharmaceuticals Ltd

  STUDY CHAIR

• Gregory Siller

  Central Brisbane Dermatology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2020
• First Posted: June 4, 2020
• Study Start: July 16, 2020
• Primary Completion: February 14, 2024
• Study Completion: February 14, 2024
• Last Updated: April 10, 2024

Record last verified: 2024-04

Locations

AU (7)