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A Clinical Study of T3011 in Patients With Advanced Cutaneous or Subcutaneous Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04370587
Recruitment Status : Recruiting
First Posted : May 1, 2020
Last Update Posted : September 24, 2020
Information provided by (Responsible Party):
ImmVira Pharma Co. Ltd

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.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Soft Tissue Tumor and/or Sarcoma Neoplasm of Skin Neoplasm Metastasis Melanoma Lung Cancer Solid Tumor Biological: T3011 Phase 1

Detailed Description:

This is a phase 1, open-label, first-in-human study of T3011 monotherapy. The study will be conducted in 2 parts: Part 1 Dose Escalation and Part 2 Dose Expansion. The objectives of this study are to evaluate the safety and tolerability of escalating doses of T3011, and to determine the Maximum Tolerated Dose (MTD) or the recommended dose(s) of T3011 by Safety Review Committee (SRC) to be further examined during Part 2. In both parts, the safety, tolerability, pharmacokinetics (PK), viral shedding, immunogenicity, and clinical activity of T3011 will be evaluated. Pharmacodynamics (PD) markers related to T3011 exposure will be characterized.

Part 1 will include up to 4 dose levels (from 1E+6 PFU/mL (plaque-forming unit/milliliter) to 1E+8 PFU/mL) of 3-6 patients at each dose, enrolling a maximum of 24 patients. Approximately 30 patients will be enrolled into Part 2 Dose Expansion.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multiple-Ascending Dose Study of the Safety and Tolerability of T3011 in Advanced Cutaneous or Subcutaneous Malignancies
Actual Study Start Date : May 30, 2020
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma

Arm Intervention/treatment
Experimental: Escalating doses of T3011 Injection
Dose escalation study of T3011 with 4 cohorts from 1E+6 pfu/mL to 1E+8 pfu/mL
Biological: T3011
Intratumoral injection of maximum 4mL at each dose level

Experimental: Dose expansion of T3011 with recommended dose
Does expansion with MTD or SRC recommended dose from Arm 1
Biological: T3011
Intratumoral injection at dose of MTD established in Arm 1 or recommended by SRC.

Primary Outcome Measures :
  1. Safety and tolerability of T3011 in dose escalating administration in patients with advanced cutaneous or subcutaneous malignancies [ Time Frame: From first dose of T3011 (Week 1 Day 1) until 60 days after the last T3011 injection (up to 2 years) ]
    Number of participants in dose escalating arm with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

  2. Safety and tolerability of T3011 in dose expansion administration in patients with advanced cutaneous or subcutaneous malignancies [ Time Frame: From first dose of T3011 (Week 1 Day 1) until 60 days after the last T3011 injection (up to 2 years) ]
    Number of participants in dose expansion arm with treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

Secondary Outcome Measures :
  1. Presence and frequency of T3011 in serum, saliva, urine, and injection site/dressing [ Time Frame: Up to 24 months ]
    To evaluate the virus shedding following intratumoral injection

  2. Quantitative measurements of serum IL-12 and anti-PD-1 antibody concentration. [ Time Frame: Up to 24 months ]
    To evaluate IL-12 and anti-PD-1 antibody expression of T3011 post intervention.

  3. Presence of neutralizing antibodies of anti-PD-1 antibody for antidrug antibodies (ADAs) development [ Time Frame: Up to 24 months ]
    To evaluate the immunogenicity of anti-PD-1 antibody expressed by T3011 post intervention.

  4. Presence of anti-herpes simplex virus type 1 (HSV-1) antibody compared to baseline [ Time Frame: Up to 24 months ]
    To evaluate the immunogenicity of T3011 viral vector post intervention.

  5. Overall response rate (ORR) [ Time Frame: Up to 24 months ]
    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.

  6. Disease control rate (DCR) [ Time Frame: Up to 24 months ]
    DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on assessments per RECIST 1.1.

  7. Duration of response (DOR). [ Time Frame: Up to 24 months ]
    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.

  8. Durable response (DR) [ Time Frame: Up to 24 months ]
    DR is defined as objective response (CR or PR) according to RECIST 1.1, with a duration of at least 6 months.

  9. Survival (assessment per RECIST 1.1 and immune-modified RECIST (imRECIST)). [ Time Frame: Up to 24 months ]
    To evaluate the progression free survival (PFS) and overall survival (OS) of participants.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key Inclusion Criteria:

  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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04370587

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United States, Arizona
Banner MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States, 85234
Contact: Brenda Noggy   
Principal Investigator: Jason Niu, MD,PhD         
United States, Texas
Mary Crowley Cancer Research Recruiting
Dallas, Texas, United States, 75230
Contact: Dr. Barve, MD   
Principal Investigator: Minal Barve, MD         
Southern Oncology Recruiting
Bedford Park, Australia
Contact: Dr.Kichenadasse   
Principal Investigator: Ganessan Kichenadasse         
Peninsula & South Eastern Haematology and Oncology Group Recruiting
Frankston, Australia
Contact: Dr. Ganju   
Principal Investigator: Vinod Ganju, A/Prof         
The Alfred Recruiting
Melbourne, Australia
Contact: Dr.Haydon   
Principal Investigator: Andrew Haydon, PhD         
Sponsors and Collaborators
ImmVira Pharma Co. Ltd
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Responsible Party: ImmVira Pharma Co. Ltd Identifier: NCT04370587    
Other Study ID Numbers: CTIV1708
First Posted: May 1, 2020    Key Record Dates
Last Update Posted: September 24, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasm Metastasis
Soft Tissue Neoplasms
Skin Neoplasms
Neoplastic Processes
Pathologic Processes
Neoplasms by Site
Skin Diseases