NCT04416516

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

A Phase 2A Study to Assess the Safety and Efficacy of ASN-002 Combined With a Hedgehog Pathway Inhibitor in the Treatment of Multiple Low Risk Basal Cell Carcinomas in Sporadic or Basal Cell Nevus Syndrome Patients

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: Ascend Biopharmaceuticals Ltd · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objectives are to: 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. Evaluate the efficacy of intralesional ASN-002 in target tumours when administered in combination with oral vismodegib in patients with BCCs. The secondary objective is to: 1\) Evaluate the efficacy of intralesional ASN-002 in non-target tumours when administered in combination with oral vismodegib in patients with BCCs. The exploratory objective is to: 1\) Evaluate immunological biomarkers during the course of treatment.

Detailed description

Methodology: This study will evaluate ASN-002 (in the dose range 0.5 to 1.5x10(11) vp/mL) with the Hh inhibitor vismodegib (Erivedge®). The study will initially evaluate two Arms receiving 1.0 x 10(11) vp/injection, and following a safety review, may implement further arms in an adaptive study design. Following screening and baseline biopsies for target and non-target tumours, eligible subjects will be enrolled in the study. Cycle 1: Treatment with vismodegib (daily dose of 150 mg) for 4 weeks and ASN-002 for 3 weeks (i.e., three ASN-002 injections in total): * Day 1 to Day 14 - vismodegib alone * Day 15 - vismodegib and ASN-002 * Day 16 to Day 21 - vismodegib alone * Day 22 - vismodegib and ASN-002 * Day 23 to Day 28 - vismodegib alone * Day 29 - ASN-002 alone Clinical response will be assessed at Week 17, following which, the investigator may where clinically indicated, initiate Cycle 2. Cycle 2: Treatment with vismodegib (daily dose of 150 mg) for 4 weeks, and one further injection with ASN-002: * Day 1 to Day 7 - vismodegib alone * Day 8 - vismodegib and ASN-002 * Day 9 to Day 28 - vismodegib alone Surgical excision for all patients will occur between Week 25 and Week 33 at the investigators discretion, and dependent on when patient completed study treatment (1 or 2 treatment cycles). Up to 10 BCCs to be excised including 3 target tumours. Excisions can be conducted over 2 visits as per Investigator's discretion. The Investigator may enrol eligible patients parallel into either Arm 1 or Arm 2, based on the number of tumours present. Up to 10 study BCC tumours (up to 3 target and up to 7 non-target) will be selected per patient. Following review of at least Week 5 data for N=6 patients in Arm 1 and Arm 2, further Arms with varying doses of ASN-002 (in the dose range 0.5x10(11) vp or 1.5x10(11) vp) may be explored at the discretion of the Safety Review Committee (SRC). Vismodegib or ASN-002 may be evaluated as monotherapies to provide control groups to allow comparison of treatment Arms. Safety and clinical assessments will be performed at Weeks 1, 3, 4, 5, 7, 17, 25 to 33. Histological response will be evaluated in all study tumours via excision between Week 25 and Week 33 (as per investigator's discretion). Six patients will be recruited to each Arm of the study, each Arm may be expanded to 12 patients at the discretion of the SRC.

Conditions

• Basal Cell Carcinoma
• Basal Cell Nevus Syndrome

Interventions

Type	Name	Description
BIOLOGICAL	ASN-002	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.

Timeline

• Start date: 2020-07-16
• Primary completion: 2024-02-14
• Completion: 2024-02-14
• First posted: 2020-06-04
• Last updated: 2024-04-10

Locations

7 sites across 1 country: Australia