A Study to Evaluate Adze1.C in Participants With Metastatic Melanoma

Official title

A Phase 1, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Preliminary Efficacy of Intratumoural Adze1.C in Participants With Metastatic Melanoma

Overview

This is Phase I, open label, multi-center clinical trial evaluating an investigational treatment, Adze1.C. Adze1.C is a type of oncolytic virus therapy for adults with advanced Melanoma that have not responded to standard treatments. Oncolytic viruses are designed to infect and destroy cancer cells and have the potential to stimulate the immune system to fight tumors. The purpose of this study is to assess preliminary efficacy, determine the safety of Adze1.C, how well it is tolerated, and to identify the highest dose that can be safely given.

Detailed description

This Phase 1, multicenter, open-label, dose-escalation study is designed to evaluate the safety, tolerability, pharmacodynamics, and preliminary efficacy of Adze1.C, a conditionally replicative oncolytic adenovirus encoding CD40L, in participants with metastatic melanoma.

Up to 30 participants will be enrolled across three sequential dose cohorts. All participants will first receive a low initial (seroconversion) dose of Adze1.C injected directly into their tumour. Three weeks later, they will receive a higher dose based on their assigned cohort:

cohort 1: Adze1.C 1 × 10E8 vp

cohort 2: Adze1.C 1 × 10E9 vp

cohort 3: Adze1.C 1 × 10E10 vp

The study will use a stepwise dose-escalation approach (3+3 design) to evaluate safety. Participants will receive injections every 2 weeks and will be monitored closely for side effects throughout the study. Safety during the first 5 weeks after starting treatment will be used to help determine whether the dose can be increased for future participants. Participants who remain eligible may continue receiving treatment for up to 14 weeks.

Interventions

• Drug Adze1.C
  Conditionally replicative oncolytic adenovirus expressing CD40L, administered by intratumoural injection in dose escalation cohorts.

Primary outcome measures

• Incidence and severity of treatment-emergent adverse events (TEAEs) [Time frame: From Day 1 (first dose) through Week 16 (end of treatment visit)]
• Incidence of dose-limiting toxicities (DLTs) [Time frame: Week 1 Day 1 to Week 6 Day 1 (5-week DLT evaluation period)]

Secondary outcome measures (5)

• Recommended Phase 2 Dose (RP2D) determination [Time frame: Through Week 16]
• Detection of viral shedding in bodily fluids [Time frame: From Day 1 through Week 16]
• Objective response rate (ORR) [Time frame: From first dose through disease progression (estimated up to 6 months)]
• Progression-Free Survival (PFS) [Time frame: From first dose to disease progression or death (estimated up to 12 months)]
• Patient-reported quality of life using EORTC QLQ-C30 [Time frame: From baseline to Week 16]

Eligibility criteria

Inclusion criteria

• Male or female participants aged 18 years or older at Screening.
• Histologically confirmed unresectable Stage IIIB to IV metastatic melanoma.
• Refractory to, or unsuitable for, standard treatment options as determined by the investigator.
• Not a suitable candidate for curative resection.
• Presence of measurable disease per iRECIST (excluding irradiated lesions unless progression post-radiation is documented).
• Presence of at least one injectable melanoma lesion and/or tumor-involved lymph node suitable for intratumoral administration.
• ECOG performance status of 0 or 1 at Screening.
• Stable visceral metastases and stable CNS metastases may be eligible if protocol-defined eligibility requirements are met.
• Willing and able to provide written informed consent and comply with study procedures.

Exclusion criteria

• Uncontrolled intercurrent illness, including but not limited to:

• Active systemic infection or fever ≥ 38°C within 5 days prior to Screening
• Symptomatic congestive heart failure
• NYHA Class III or IV heart failure
• Unstable angina or arrhythmia
• Leptomeningeal disease, active uncontrolled or symptomatic brain metastases, CNS haemorrhage, uncontrolled peri-tumoural oedema, or conditions associated with high risk of CNS inflammation
• Psychiatric illness or social conditions that limit compliance
• Visceral metastatic disease that is not clinically and radiographically stable or requires urgent medical intervention.
• Immunocompromised status or known HIV infection with ongoing antiretroviral therapy.
• Active or clinically significant liver disease, including:

• Hepatitis B surface antigen (HBsAg) positive
• Hepatitis C virus RNA positive
• History of organ transplantation.
• Prior treatment with adenovirus therapy.
• Prior oncolytic virus treatment within 2 months of Screening.
• Use of systemic immunosuppressants or other immune-modifying drugs must be discontinued 14 days prior to the first dose.
• Use of cidofovir within 14 days of Adze1.C dosing.
• Any other condition which, in the investigator's judgment, would make the participant inappropriate for the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 3 centers

• Tasman Oncology Research — Southport
• The Queen Elizabeth Hospital — Adelaide
• Monash Health — Clayton

Identifiers

NCT: NCT07086105 · ADZE1.C-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗