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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04370587




Registration number
NCT04370587
Ethics application status
Date submitted
14/04/2020
Date registered
1/05/2020
Date last updated
4/02/2021

Titles & IDs
Public title
A Clinical Study of T3011 in Patients With Advanced Cutaneous or Subcutaneous Malignancies
Scientific title
A Phase 1, Open-Label, Multiple-Ascending Dose Study of the Safety and Tolerability of T3011 in Advanced Cutaneous or Subcutaneous Malignancies
Secondary ID [1] 0 0
CTIV1708
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and Neck Cancer 0 0
Soft Tissue Tumor and/or Sarcoma 0 0
Neoplasm of Skin 0 0
Neoplasm Metastasis 0 0
Melanoma 0 0
Lung Cancer 0 0
Solid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Non melanoma skin cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - T3011
Other interventions - T3011

Experimental: Escalating doses of T3011 Injection - Dose escalation study of T3011 with 4 cohorts from 1E+6 pfu/mL to 1E+8 pfu/mL

Experimental: Dose expansion of T3011 with recommended dose - Does expansion with MTD or SRC recommended dose from Arm 1


Other interventions: T3011
Intratumoral injection of maximum 4mL at each dose level

Other interventions: T3011
Intratumoral injection at dose of MTD established in Arm 1 or recommended by SRC.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability of T3011 in dose escalating administration in patients with advanced cutaneous or subcutaneous malignancies - Number of participants in dose escalating arm with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.
Timepoint [1] 0 0
From first dose of T3011 (Week 1 Day 1) until 60 days after the last T3011 injection (up to 2 years)
Primary outcome [2] 0 0
Safety and tolerability of T3011 in dose expansion administration in patients with advanced cutaneous or subcutaneous malignancies - Number of participants in dose expansion arm with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.
Timepoint [2] 0 0
From first dose of T3011 (Week 1 Day 1) until 60 days after the last T3011 injection (up to 2 years)
Secondary outcome [1] 0 0
Presence and frequency of T3011 in serum, saliva, urine, and injection site/dressing - To evaluate the virus shedding following intratumoral injection
Timepoint [1] 0 0
Up to 24 months
Secondary outcome [2] 0 0
Quantitative measurements of serum IL-12 and anti-PD-1 antibody concentration. - To evaluate IL-12 and anti-PD-1 antibody expression of T3011 post intervention.
Timepoint [2] 0 0
Up to 24 months
Secondary outcome [3] 0 0
Presence of neutralizing antibodies of anti-PD-1 antibody for antidrug antibodies (ADAs) development - To evaluate the immunogenicity of anti-PD-1 antibody expressed by T3011 post intervention.
Timepoint [3] 0 0
Up to 24 months
Secondary outcome [4] 0 0
Presence of anti-herpes simplex virus type 1 (HSV-1) antibody compared to baseline - To evaluate the immunogenicity of T3011 viral vector post intervention.
Timepoint [4] 0 0
Up to 24 months
Secondary outcome [5] 0 0
Overall response rate (ORR) - ORR is defined as the proportion of participants who have a partial response (PR) or complete response (CR) to intervention, based on assessments per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Timepoint [5] 0 0
Up to 24 months
Secondary outcome [6] 0 0
Disease control rate (DCR) - DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on assessments per RECIST 1.1.
Timepoint [6] 0 0
Up to 24 months
Secondary outcome [7] 0 0
Duration of response (DOR). - DOR is defined as the time from the first met CR or PR until disease progression or death due to any cause, whichever occurs first.
Timepoint [7] 0 0
Up to 24 months
Secondary outcome [8] 0 0
Durable response (DR) - DR is defined as objective response (CR or PR) according to RECIST 1.1, with a duration of at least 6 months.
Timepoint [8] 0 0
Up to 24 months
Secondary outcome [9] 0 0
Survival (assessment per RECIST 1.1 and immune-modified RECIST (imRECIST)). - To evaluate the progression free survival (PFS) and overall survival (OS) of participants.
Timepoint [9] 0 0
Up to 24 months

Eligibility
Key inclusion criteria
Key

1. Age 18 years or older.

2. Histologically confirmed diagnosis of cutaneous or subcutaneous advanced malignancy.

3. Measurable disease per RECIST version 1.1.

4. Must have at least 1 injectable tumor lesion.

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. Life expectancy > 12
weeks.

7. Demonstrate adequate organ function as defined by acceptable laboratory testing
results.

8. Women of child-bearing potential (WCBP) and men must agree to use adequate
contraception prior to study entry and for the first six months after receiving T3011.
And WCBP must have a negative serum pregnancy test prior to study.

9. Last dose of previous anticancer therapy = 28 days, radiotherapy > 21 days, or
surgical intervention > 21 days prior to the first dose of T3011.

10. Recovered from all prior anticancer therapy toxicities.

11. Willingness to provide fresh tumor biopsy specimens as specified in the Schedule of
Assessments.

12. Capable of understanding and complying with protocol requirements.

13. Signed and dated institutional review board/independent ethics committee-approved
informed consent form before any protocol-directed screening procedures are performed.

Key
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Have only tumors with severe fibrosis and therefore not injectable.

2. Patients with injectable tumors 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

5. Systemic therapy with immunosuppressive agents within 28 days before the start of
T3011 treatment

6. Live vaccines within 4 weeks of initiation of study treatment.

7. Primary or acquired immunodeficient states (leukemia, 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

12. History of or current central nervous system metastases

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, 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 to HSV-1, IL-12, or anti-PD-1 monoclonal antibody.

19. Known or active suspected infection 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Southern Oncology - Bedford Park
Recruitment hospital [2] 0 0
Peninsula & South Eastern Haematology and Oncology Group - Frankston
Recruitment hospital [3] 0 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 0 0
- Bedford Park
Recruitment postcode(s) [2] 0 0
- Frankston
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ImmVira Pharma Co. Ltd
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
PPD
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
A phase 1, open-label, first-in-human study of T3011 monotherapy to evaluate the safety and
tolerability of T3011 in patients with advanced cancers with cutaneous or subcutaneous tumor
deposits who have progressed while receiving standard of care therapy or who will not benefit
from such therapy.
Trial website
https://clinicaltrials.gov/show/NCT04370587
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04370587