Clinical Trials /

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

NCT04370587

Description:

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.

Related Conditions:
  • Head and Neck Carcinoma
  • Malignant Skin Neoplasm
  • Malignant Soft Tissue Neoplasm
  • Melanoma
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Clinical Study of T3011 in Patients With Advanced Cutaneous or Subcutaneous Malignancies
  • Official Title: A Phase 1, Open-Label, Multiple-Ascending Dose Study of the Safety and Tolerability of T3011 in Advanced Cutaneous or Subcutaneous Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CTIV1708
  • NCT ID: NCT04370587

Conditions

  • Head and Neck Cancer
  • Soft Tissue Tumor and/or Sarcoma
  • Neoplasm of Skin
  • Neoplasm Metastasis
  • Melanoma

Interventions

DrugSynonymsArms
T3011Escalating doses of T3011 Injection
T3011Dose expansion of T3011 with recommended dose

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Escalating doses of T3011 InjectionExperimentalDose escalation study of T3011 with 4 cohorts from 1E+6 pfu/mL to 1E+8 pfu/mL
  • T3011
Dose expansion of T3011 with recommended doseExperimentalDoes expansion with MTD or SRC recommended dose from Arm 1
  • T3011

Eligibility Criteria

        Key Inclusion Criteria:

          1. Age 18 years or older.

          2. Histologically confirmed diagnosis of cutaneous and 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.

         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. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:Number of participants in dose escalating arm with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

Secondary Outcome Measures

Measure:Presence and frequency of T3011 in serum, saliva, urine, and injection site/dressing
Time Frame:Up to 24 months
Safety Issue:
Description:To evaluate the virus shedding following intratumoral injection
Measure:Quantitative measurements of serum IL-12 and anti-PD-1 antibody concentration.
Time Frame:Up to 24 months
Safety Issue:
Description:To evaluate IL-12 and anti-PD-1 antibody expression of T3011 post intervention.
Measure:Presence of neutralizing antibodies of anti-PD-1 antibody for antidrug antibodies (ADAs) development
Time Frame:Up to 24 months
Safety Issue:
Description:To evaluate the immunogenicity of anti-PD-1 antibody expressed by T3011 post intervention.
Measure:Presence of anti-herpes simplex virus type 1 (HSV-1) antibody compared to baseline
Time Frame:Up to 24 months
Safety Issue:
Description:To evaluate the immunogenicity of T3011 viral vector post intervention.
Measure:Overall response rate (ORR)
Time Frame:Up to 24 months
Safety Issue:
Description: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.
Measure:Disease control rate (DCR)
Time Frame:Up to 24 months
Safety Issue:
Description:DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on assessments per RECIST 1.1.
Measure:Duration of response (DOR).
Time Frame:Up to 24 months
Safety Issue:
Description: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.
Measure:Durable response (DR)
Time Frame:Up to 24 months
Safety Issue:
Description:DR is defined as objective response (CR or PR) according to RECIST 1.1, with a duration of at least 6 months.
Measure:Survival (assessment per RECIST 1.1 and immune-modified RECIST (imRECIST)).
Time Frame:Up to 24 months
Safety Issue:
Description:To evaluate the progression free survival (PFS) and overall survival (OS) of participants.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:ImmVira Pharma Co. Ltd

Last Updated

April 28, 2020