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A Clinical Study of T3011 When Administered Via Intravenous Infustion in Patients With Advanced or Metastatic Solid Tumors

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ClinicalTrials.gov Identifier: NCT04780217
Recruitment Status : Not yet recruiting
First Posted : March 3, 2021
Last Update Posted : March 3, 2021
Sponsor:
Information provided by (Responsible Party):
ImmVira Pharma Co. Ltd

Brief Summary:
This is a Phase 1/2a open-label study of T3011 when administered via IV as a single agent and in combination with pembrolizumab, to evaluate safety, tolerability, preliminary clinical activity in patients with advanced or metastatic solid tumors in dose escalation portion (Phase 1 Part A and Part B) or patients with NSCLC, solid tumors with metastasis in liver and/or lung in dose expansion portion (Phase 2a), who have relapsed, or are refractory to or are not considered medically suitable to receive standard of care (SOC) treatment.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Soft Tissue Tumor and/or Sarcoma Neoplasm of Skin Neoplasm Metastasis Melanoma Nsclc Metastasis in Lung Metastasis in Liver Solid Tumor Biological: T3011 Combination Product: T3011+Pembrolizumab Phase 1 Phase 2

Detailed Description:

This is a Phase 1/2a open-label study of T3011 as a single agent and in combination with pembrolizumab. The Phase 1 portion of the study will be conducted in 2 parts: Part A dose escalation of single agent T3011 and Part B dose escalation of T3011 in combination with pembrolizumab. The Phase 2a portion will evaluate T3011 in combination with pembrolizumab. The objectives of the Phase 1 are to evaluate the safety and tolerability of escalating doses of T3011 alone and in combination with pembrolizumab, and to determine the dose(s) of T3011 to be further examined. During Phase 2a, the safety and tolerability of T3011 in combination with pembrolizumab at the dose selected in Phase 1 Part B will be evaluated. The safety, pharmacokinetic (PK) and viral shedding, immunogenicity, and clinical activity of T3011 will be evaluated. Pharmacodynamic markers related to T3011 exposure will be characterized.

This study will enroll patients with pathologically confirmed locally recurrent or metastatic solid tumors (Phase 1 Part A and Part B) or patients with histologically and cytologically confirmed NSCLC that is recurrent or metastatic or histologically or cytologically diagnosed advanced solid tumors with metastasis in liver and/or lung (Phase 2a), who have relapsed, or are refractory to or are not considered medically suitable to receive standard of care (SOC) treatment. These patients represent a population with a high unmet need. Patients will be informed of available treatment options and, in consultation with the study Investigator, will decide whether or not to participate in the T3011 study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a Open-Label Dose Escalation and Dose Expansion Study of T3011 When Administered Via Intravenous Infusion as a Single Agent and in Combination With Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors
Estimated Study Start Date : April 2021
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma

Arm Intervention/treatment
Experimental: Single Agent T3011 Dose Escalation Biological: T3011
T3011 will be administered in a 10 mL solution as an IV infusion over 15 minutes (± 5 minutes).

Experimental: T3011 Dose Escalation in Combination with Pembrolizumab Combination Product: T3011+Pembrolizumab
T3011 will be administered in a 10 mL solution as an IV infusion over 15 minutes (± 5 minutes), followed by administration of pembrolizumab as an IV infusion at least 30 minutes after the completion of T3011 dosing.

Experimental: Dose expansion of T3011 in Combination with Pembrolizumab with recommended dose Combination Product: T3011+Pembrolizumab
T3011 will be administered in a 10 mL solution as an IV infusion over 15 minutes (± 5 minutes), followed by administration of pembrolizumab as an IV infusion at least 30 minutes after the completion of T3011 dosing.




Primary Outcome Measures :
  1. Safety and tolerability of escalating doses of single agent IV T3011 (Part A) and and of IV T3011 in combination with pembrolizumab (Part B). [ Time Frame: From first dose of single agent IV T3011 and IV T3011 in combination with pembrolizumab (D1 of Cycle1, each cycle consists 21 days) untill at 30 (± 5) days after the last dose of study treatment (up to 2 years) ]
    Number of participants in both dose escalating arms (Single agent IV T3011 and combination) with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.

  2. The maximum tolerated dose (MTD) and/or the recommended dose (RD) of single agent IV T3011 (Part A) . [ Time Frame: From the first dose of single agent IV T3011 untill the end of dose escalation in Part A study, up to 24 months ]
    Identification of MTD and/or RD in Part A study.

  3. The MTD and/or the recommended phase 2 dose (RP2D) of IV T3011 in combination with pembrolizumab (Part B). [ Time Frame: From the first dose of IV T3011 in combination with Pembrolizumab untill the end of dose escalation in Part B study, up to 24months. ]
    Identification of the MTD and/or RP2D of IV T3011 in combination with Pembrolizumab (Part B) .

  4. Safety and tolerability of the RP2D of IV T3011 in combination with pembrolizumab selected from Phase 1 Part B in disease specific cohorts. [ Time Frame: From first dose in phase 2a (D1 of Cycle1,each cycle consists 21 days) untill at 30 (± 5) days after the last dose of study treatment (up to 2 years) ]
    Number of participants in dose expansion arm (Phase 2a) with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), and/or changes in clinical laboratory abnormalities.


Secondary Outcome Measures :
  1. Quantitative viral DNA level of T3011 in urine and saliva. [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    To evaluate viral shedding in participants dosed with single agent IV T3011 and IV T3011 in combination with Pembrolizumab.

  2. Quantitative measurements of blood viral DNA level, serum IL-12 and anti-PD-1 antibody concentrationIL-12 and anti-PD-1 antibody concentration. [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    To evaluate the pharmacokinetic (PK) of single agent IV T3011 and of IV T3011 in combination with pembrolizumab.

  3. Presence of anti-herpes simplex virus type 1 (HSV-1) immunoglobulin G (IgG) and anti-PD-1 idiotypic antibody. [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    To evaluate the immunogenicity of single agent IV T3011 and of IV T3011 in combination with pembrolizumab.

  4. Overall response rate (ORR) [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    ORR is defined as the proportion of participants who have a partial response (PR) or complete response (CR) to intervention, based on investigator assessments per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and iRECIST, to evaluate the preliminary clinical activity of single agent IV T3011 (Part A) and of IV T3011 in combination with pembrolizumab (Part B) and of treatment in Phase 2a.

  5. Disease control rate (DCR) [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on investigator assessments per RECIST 1.1 and iRECIST, to evaluate the preliminary clinical activity of single agent IV T3011 (Part A) and of IV T3011 in combination with pembrolizumab (Part B) and of treatment in Phase 2a.

  6. Duration of response (DOR) [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    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, to evaluate the preliminary clinical activity of single agent IV T3011 (Part A) and of IV T3011 in combination with pembrolizumab (Part B) and of treatment in Phase 2a.

  7. Durable response (DR) [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    DR is defined as objective response (CR or PR) according to RECIST 1.1, to evaluate the preliminary clinical activity of single agent IV T3011 (Part A) and of IV T3011 in combination with pembrolizumab (Part B) and of treatment in Phase 2a.

  8. Progression-free survival (PFS) [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    PFS is defined as the time from enrollment to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first per RECIST 1.1 and iRECIST, to evaluate the preliminary clinical activity of single agent IV T3011 (Part A) and of IV T3011 in combination with pembrolizumab (Part B) and of treatment in Phase 2a.

  9. Overall survival (OS) [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    OS is defined as the time from enrollment to death from any cause, to evaluate the preliminary clinical activity of single agent IV T3011 (Part A) and of IV T3011 in combination with pembrolizumab (Part B) and of treatment in Phase 2a.


Other Outcome Measures:
  1. Expression level of IL-12/anti-PD-1 antibody. [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    Assess expression the potential predictive biomarker post-dosing.

  2. Assessment of tumor genomics. [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    Sequencing analysis of biopsied samples

  3. Tumor environment reponse to treatment. [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    IF analysis of biopsied samples

  4. Assessment of systemic immune response [ Time Frame: From the first dose untill the EOT in each portion of study (up to 2 years). ]
    Assess the lymphocyte profiling and level of blood cytokine



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Participants with one of the following cancers:

    • Pathologically confirmed, locally recurrent or metastatic solid tumors (Phase 1 Part A and B)
    • Histologically or cytologically confirmed NSCLC that is recurrent or metastatic (Phase 2a)
    • Histologically or cytologically diagnosed advanced solid tumors with metastasis in liver and/or lung (Phase 2a).
  2. Disease progression after SOC therapy or in the opinion of the Investigator unlikely to benefit from SOC therapy.
  3. Age 18 years or older.
  4. Measurable disease per RECIST version 1.1.
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
  6. Life expectancy > 12 weeks.
  7. Adequate bone marrow function defined by absolute neutrophil count (ANC) of ≥ 1.5 × 10^9/L, platelet count of ≥ 100 × 10^9/L, and hemoglobin of ≥ 8.5 g/dL.
  8. Adequate hepatic function defined as aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN) and total bilirubin ≤ 1.5 × ULN (except patients with Gilbert's Syndrome, who can have total bilirubin < 3.0 mg/dL).
  9. Adequate renal function defined as creatinine clearance > 50 mL/min as determined by the Cockcroft-Gault equation.
  10. Female participants must be surgically sterile (or have a monogamous partner who is surgically sterile), or be at least 2 years postmenopausal, or commit to using 2 acceptable forms of birth control 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 for the duration of the study and for 6 months following the last dose of study treatment.
  11. Women of childbearing potential (WCBP) must have a negative serum pregnancy test at Screening within 14 days of dosing with T3011 and a negative urine pregnancy test pre-dose on C1D1.
  12. Last dose of previous anticancer therapy ≥ 21 days; radiotherapy > 21 days (except prior focal palliative radiotherapy must have been completed at least 1 week prior to the first dose of study treatment); major surgery > 21 days; or last dose of therapy with tyrosine kinase inhibitors within 5 times the half-life of the inhibitor prior to first dose of study treatment. Last dose of checkpoint inhibitor ≥ 14 days, as long as treatment related toxicities resolve to ≤ Grade 1.
  13. Resolution of all prior anticancer therapy toxicities (except for alopecia) to ≤ Grade 1. Note: patients previously treated with immunotherapy may enroll if on adequate replacement therapy. Patients with toxicities attributed to systemic prior anticancer therapy, which are not expected to resolve and result in long lasting sequelae are permitted to enroll.
  14. Willingness to provide pre- and post-treatment fresh tumor biopsy specimens. Participant may be eligible to participate without providing fresh tumor biopsy specimens, following discussion with and approval from the Medical Monitor.
  15. Capable of understanding and complying with protocol requirements.
  16. Signed and dated institutional review board/independent ethics committee (IRB/IEC) approved informed consent form (ICF) before any protocol-directed screening procedures are performed.

Exclusion Criteria:

  1. Prior treatment with another OV or cellular therapy.
  2. Previous unacceptable intolerance to anti-PD-1 monoclonal antibody.
  3. Requires continued concurrent systemic therapy with any drug active against HSV. Topical use of drugs against HSV are allowed.
  4. Live vaccines within 4 weeks of initiation of study treatment.
  5. Primary or acquired immunodeficient states.
  6. Pregnant or lactating.
  7. Splenectomy, previous allogenic tissue/solid organ transplant.
  8. Active hepatitis B virus, hepatitis C virus, or a positive serological test at Screening.

    • Patients who test positive for anti-HCV Ab but negative for HCV ribonucleic acid (RNA) are considered eligible to participate in the study.
    • Patients who are HBsAg+ and/or HBcAb+ and have a DNA load < 2000 IU/mL (104 copies/mL) are considered eligible to participate in the study.
  9. Active autoimmune disease or other medical conditions requiring chronic systemic steroid (> 10 mg/day prednisone or equivalent) or immunosuppressive therapy within 6 months prior to first administration of study treatment (unless agreed otherwise between the Medical Monitor and the Investigator on a case-by-case basis). Non-systemic corticosteroids (eg, topical, inhaled) are allowed.
  10. Patients with untreated and/or symptomatic metastatic central nervous system (CNS) disease. However, patients with brain/CNS metastases who have undergone surgery or radiotherapy, whose disease is stable and who have been on a stable dose of corticosteroids (≤ 10 mg prednisone or equivalent) for at least 4 weeks prior to the first administration of study treatment will be eligible.
  11. History of seizure disorders within 6 months of Screening.
  12. Active oral or skin herpes lesion at Screening.
  13. 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.
  14. History of allergic reactions attributed to compounds of similar biological composition to HSV-1, IL-12, or anti-PD-1 monoclonal antibody or their excipients.
  15. Known or suspected active infection with SARS-CoV-2 virus.
  16. 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.
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Responsible Party: ImmVira Pharma Co. Ltd
ClinicalTrials.gov Identifier: NCT04780217    
Other Study ID Numbers: MVR-T3011-003
First Posted: March 3, 2021    Key Record Dates
Last Update Posted: March 3, 2021
Last Verified: February 2021

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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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Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Soft Tissue Neoplasms
Skin Neoplasms
Neoplastic Processes
Pathologic Processes
Neoplasms by Site
Skin Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents