None listed
Conditions
Brief summary
The purpose of this study is to assess the safety of a genetically modified virus, called T3011 in advanced cancer Who is it for? You may be eligible for this study if you are aged 18 or over and have advanced cancer presenting with a skin or subcutaneous (under the skin) malignancy. Study details All participants in this study will have injections into their tumour(s). These injections will contain the genetically modified virus T3011, which is oncolytic – this means it bursts open cancer cells. The dose administered will increase for each new cohort until the maximum tolerated dose is identified. Participants will have the injection every 2 weeks for up to 2 years, depending on how well the treatment is tolerated. As part of the study, participants will provide saliva, blood and urine samples. It is hoped this research will provide some safety data for T3011 and identify the appropriate dose of T3011 for bigger clinical trials.
Interventions
Intervention = Investigational Product = T3011, a genetically modified oncolytic virus.
Participants will receive T3011 at the assigned dose level by intratumoural injection commencing on W1D1, and approximately every 14 days thereafter (ie: W3D1, W5D1 etc) for up to 2 years (unless disease progression, unacceptable toxicity, death or withdrawal of consent).
Part 1 – Dose Escalation
The starting dose of T3011 is 1.0 × 10^6 PFU/mL with the volume injected intratumourally based on tumour size,
Intervention = Investigational Product = T3011, a genetically modified oncolytic virus. Participants will receive T3011 at the assigned dose level by intratumoural injection commencing on W1D1, and approximately every 14 days thereafter (ie: W3D1, W5D1 etc) for up to 2 years (unless disease progression, unacceptable toxicity, death or withdrawal of consent). Part 1 – Dose Escalation The starting dose of T3011 is 1.0 × 10^6 PFU/mL with the volume injected intratumourally based on tumour size, but not exceeding a total of 4 mls for each visit for all tumours combined. The study uses a 3+3 dose escalation design to evaluate escalating doses of T3011 monotherapy. Three additional doses are planned to be tested (1.0 × 10^7, 5.0 × 10^7, and 1 × 10^8 PFU/ml). At any dose level, if no dose-limiting toxicity (DLT) occurs among the first 3 participants, then escalation to the next dose level may proceed if approved by the Safety Review committee (SRC). If 1 DLT occurs in the first 1 to 3 participants, the dose level will expand to a maximum of 6 participants. If no DLT occurs among the additional participants, then escalation to the next dose level may proceed if approved by the SRC. The non-tolerated dose (NTD) is the dose level at which 2 or more participants experience a DLT during the DLT evaluation period. The maximum tolerated dose (MTD) will be defined as the dose level immediately below the NTD. At least 6 participants will be treated at the MTD before expansion to Part 2 (Dose Expansion) with additional participants treated with a dose selected by the SRC.
Sponsors
Theravir Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. See Age criteria 2. Histologically confirmed diagnosis of cutaneous OR subcutaneous advanced malignancy. 3. Measurable disease per RECIST version 1.1. 4. Must have at least 1 tumour lesion with a longest dimension of greater than or equal to 10 mm (greater than or equal to 15 mm for the short axis for malignant lymph node lesions) that can be easily palpated or detected by ultrasound to facilitate IT injection of T3011 (ie, tumour in skin, muscle, subcutaneous tissue, or accessible lymph node). 5. Disease progression after standard-of-care (SOC) therapy or in the opinion of the Investigator unlikely to benefit from SOC therapy. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 7. Life expectancy > 12 weeks. 8. Adequate bone marrow function defined by ANC of greater than or equal to 1.5 × 10^9/L, platelet count of greater than or equal to 100.0 × 10^9/L, and hemoglobin of greater than or equal to 90 g/L (with or without transfusion). 9. Adequate hepatic function defined as serum total bilirubin < 2.5 × ULN, AST/ALT of less than or equal to 2.5 × ULN (or less than or equal to 5 × ULN in participants with liver metastases). 10. Adequate renal function defined as creatinine clearance > 50 mL/min as determined by the Cockcroft-Gault equation. 11. Female participants must be surgically sterile (or have a monogamous partner who is surgically sterile), or be least 2 years postmenopausal, or commit to using 2 acceptable forms of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence) for the duration of the study and for 6 months following the last dose of study treatment. Male participants must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study and for 6 months following the last dose of study treatment. 12. Women of childbearing potential (WCBP) must have a negative serum pregnancy test at Screening within 7 days of dosing with T3011. 13. Last dose of previous anticancer therapy greater than or equal to 28 days, radiotherapy > 21 days (concurrent targeted palliative radiotherapy is allowed to non-injected lesions during T3011 treatment), or surgical intervention > 21 days prior to the first dose of T3011. 14. Resolution of all prior anticancer therapy toxicities (except for alopecia) to less than or equal to Grade 1. Note: patients previously treated with immunotherapy who have endocrinopathies may enrol if on adequate replacement therapy. 15. Willingness to provide pre- and post-treatment fresh tumour biopsy specimens. 16. Capable of understanding and complying with protocol requirements. 17. Signed and dated institutional review board/independent ethics committee-approved informed consent form before any protocol-directed screening procedures are performed
Exclusion criteria
Have only tumours with severe fibrosis and therefore not injectable. 2. Patients with injectable tumours impinging upon major airways or blood vessels. 3. Prior treatment with another oncolytic virus or cellular therapy. 4. Requires continued concurrent therapy with any drug active against HSV (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir). 5. Systemic therapy with immunosuppressive agents within 28 days before the start of T3011 treatment; topical, intranasal, intraocular, or inhaled corticosteroids and physiologic replacement for patients with adrenal insufficiency are allowed. 6. Live vaccines within 4 weeks of initiation of study treatment. 7. Primary or acquired immunodeficient states (leukaemia, lymphoma, human immunodeficiency virus (HIV)/AIDS). 8. Pregnant or lactating. 9. Prior organ transplantation. 10. Active hepatitis B virus, hepatitis C virus, and HIV infection or a positive serological test at Screening within 14 days of dosing with T3011. Positive for HCV Ab only when HCV RNA positive at Screening. Patients who are HBsAg+ and/or HBcAb+ and have a DNA load <2000 IU/mL (10^4 copies/mL) are considered eligible to participate in the study. 11. Active autoimmune disease or medical conditions requiring chronic steroid (ie, > 10 mg/day prednisone or equivalent) or immunosuppressive therapy; patients with a prior history of autoimmune disease may be eligible following discussion with and written approval from the Medical Monitor. 12. History of or current central nervous system metastases (brain imaging [eg, by CT scan, PET scan, MRI scan, etc., per site standards] completed within 3 months of Screening [required for all participants]). 13. History of seizure disorders within 6 months of Screening. 14. Active oral herpes lesion at Screening. 15. Baseline pulse oximetry < 92% on room air. 16. Active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids. 17. Congestive heart failure (> New York Heart Association Class II), active coronary artery disease, unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest), or clinically significant cardiac arrhythmias. 18. History of allergic reactions attributed to compounds of similar biological composition. 19. Known or activie suspected infections with SARS-CoV-2 virus . 20. Other systemic conditions or organ abnormalities that, in the opinion of the Investigator, may interfere with the conduct and/or interpretation of the current study.
Outcome results
None listed