Clinical Trials /

A Study Evaluating Safety and Therapeutic Activity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors

NCT04009681

Description:

This is an open-label, First-in-Human, dose escalation and dose expansion study of THOR-707 (Monotherapy and Combination Therapy) in adult subjects with advanced or metastatic solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating Safety and Therapeutic Activity of THOR-707 in Adult Subjects With Advanced or Metastatic Solid Tumors
  • Official Title: An Open-Label, Multicenter Phase 1/2 Dose Escalation and Expansion Study of THOR-707 as a Single Agent and in Combination With a Checkpoint Inhibitor in Adult Subjects With Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: THOR-707-101
  • NCT ID: NCT04009681

Conditions

  • Solid Tumor, Unspecified, Adult

Interventions

DrugSynonymsArms
THOR-707THOR-707 Monotherapy, Q2W
Checkpoint inhibitorTHOR-707 in combination with a checkpoint inhibitor, Q3W

Purpose

This is an open-label, First-in-Human, dose escalation and dose expansion study of THOR-707 (Monotherapy and Combination Therapy) in adult subjects with advanced or metastatic solid tumors.

Detailed Description

      This is a First-in-Human, open-label, multiple ascending dose escalation and dose expansion
      study of THOR-707 in adult subjects with advanced or metastatic solid tumors. The objectives
      of the dose escalation phase are to identify the recommended phase 2 dose (RP2D) of THOR-707
      as a monotherapy (Part 1) and in combination with a checkpoint inhibitor (Part 2); to
      evaluate safety/tolerability of THOR-707; to evaluate anti-tumor activity of THOR-707; to
      evaluate pharmacokinetics of THOR-707; and to evaluate various immunological biomarkers pre-
      and post-treatment with THOR-707. The objectives of the dose expansion phase (Part 3) are to
      further evaluate safety and anti-tumor activity of THOR-707 (administered at the RP2D) as a
      monotherapy and in combination with a checkpoint inhibitor in select populations of patients
      with advanced or metastatic solid tumors.
    

Trial Arms

NameTypeDescriptionInterventions
THOR-707 Monotherapy, Q2WExperimentalDose Escalation: THOR-707 will be administered in sequential ascending doses as a monotherapy via intravenous (IV) administration every 2 weeks (Q2W) until unacceptable toxicity, disease progression, or withdrawal of consent.
  • THOR-707
THOR-707 Monotherapy, Q3WExperimentalDose Escalation: THOR-707 will be administered in sequential ascending doses as a monotherapy via IV administration every 3 weeks (Q3W) until unacceptable toxicity, disease progression, or withdrawal of consent.
  • THOR-707
THOR-707 in combination with a checkpoint inhibitor, Q3WExperimentalDose Escalation: THOR-707 will be administered in sequential ascending doses in combination with a checkpoint inhibitor via IV administration Q3W until unacceptable toxicity, disease progression, or withdrawal of consent.
  • THOR-707
  • Checkpoint inhibitor

Eligibility Criteria

        Key Inclusion Criteria:

          -  Measurable disease per RECIST v1.1.

          -  Life expectancy greater than or equal to 12 weeks.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          -  Adequate cardiovascular, hematological, liver, and renal function.

          -  Histologically or cytologically confirmed diagnosis of advanced and/or metastatic
             solid tumors with at least one tumor lesion with location accessible to safely biopsy
             per clinical judgment of the Investigator.

          -  Prior anti-cancer therapy is allowed as long as any treatment related toxicity is
             resolved to an appropriate level.

          -  Females of childbearing potential and men who are not surgically sterile must agree to
             use medically-accepted method of birth control during the study and for at least 3
             months after last dose of treatment.

          -  [Females] Negative serum pregnancy test within 7 days prior to initiating study
             treatment in premenopausal women and women less than 12 months after menopause.

          -  [Males] Agreement to refrain from donating or banking sperm during the treatment
             period and for at least 3 months after last dose of study treatment.

        Key Exclusion Criteria:

          -  Radiotherapy ≤ 14 days prior to first dose of study drug (palliative radiation or
             stereotactic radiosurgery within 7 days prior to start of study treatment).

          -  Treated with systemic anti-cancer therapy or an investigational agent within 2 weeks
             prior to start of study drug treatment (within 4 weeks for immunotherapy and tyrosine
             kinase inhibitor therapy).

          -  Major surgery ≤ 30 days prior to first dose of study drug, or has not recovered to at
             least Grade 1 from adverse effects from such procedure, or anticipation of the need
             for major surgery during study treatment.

          -  Active autoimmune disease requiring systemic treatment within the past 3 months or
             have a documented history of clinically severe autoimmune disease that requires
             systemic steroids or immunosuppressive agents.

          -  Primary central nervous system (CNS) disease or leptomeningeal disease; known CNS
             metastases unless treated, are asymptomatic, are without evidence of radiological
             progression for at least 8 weeks, and have had no requirement for steroids or enzyme
             inducing anticonvulsants in the last 14 days prior to Screening.

          -  Abnormal pulmonary function, including history of pneumonitis, active pneumonitis,
             interstitial lung disease requiring the use of steroids, idiopathic pulmonary
             fibrosis, confirmed pleural effusion, severe dyspnea at rest or requiring
             supplementary oxygen therapy.

          -  History of allogenic or solid organ transplant.

          -  Known human immunodeficiency virus (HIV) infection or active infection with hepatitis
             B or C.

          -  Clinically significant bleeding within 2 weeks prior to initial THOR-707 dose (e.g.,
             gastrointestinal bleeding, intracranial hemorrhage).

          -  Prior diagnosis of deep vein thrombosis or pulmonary embolism within 3 months.

          -  Severe or unstable cardiac condition within 6 months prior to starting study
             treatment, such as congestive heart failure (New York Heart Association Class III or
             IV), cardiac bypass surgery or coronary artery stent placement, angioplasty, cardiac
             ejection fraction below the lower limit of normal, unstable angina, medically
             uncontrolled hypertension (e.g. ≥160 mm Hg systolic or ≥100 mm Hg diastolic),
             uncontrolled cardiac arrhythmia requiring medication (≥ grade 2, according to NCI
             CTCAE v5.0), or myocardial infarction.

          -  History of non-pharmacologically induced prolonged corrected QT interval determined
             using Fridericia's formula (QTcF) > 480 milliseconds (msec).

          -  Known hypersensitivity to any components of THOR-707, PEG, pegylated drugs, or
             checkpoint inhibitors for applicable cohorts.

          -  Active second malignancy, or history of previous malignancy that would impact the
             assessment of any study endpoints. Subjects with non-melanomatous skin cancer or
             cervical cancer that has been curatively surgically resected are eligible.

          -  Any serious medical condition (including pre-existing autoimmune disease or
             inflammatory disorder), laboratory abnormality, psychiatric condition, or any other
             significant or unstable concurrent medical illness that in the opinion of the
             Investigator would preclude protocol therapy or would make the subject inappropriate
             for the study.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the screening visit through 3 months
             after the last dose of study treatment.

          -  Concurrent therapy with any other investigational agent, vaccine, or device.
             Concomitant participation in observational studies is acceptable after Sponsor
             approval.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of Dose-Limiting Toxicities (DLTs)
Time Frame:Study Day 1 up to Day 29
Safety Issue:
Description:Based on toxicities observed

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) according to RECIST version 1.1
Time Frame:Study Day 1, assessed up to 24 months
Safety Issue:
Description:Based on Investigator review of radiographic imaging.
Measure:Duration of Response (DOR) according to RECIST version 1.1
Time Frame:Study Day 1, assessed up to 24 months
Safety Issue:
Description:Based on Investigator review of radiographic imaging.
Measure:Progression-Free Survival (PFS) according to RECIST version 1.1
Time Frame:Study Day 1 until the date of first documented progression or date of death from any cause, assessed up to 24 months
Safety Issue:
Description:Based on Investigator review of radiographic imaging.
Measure:Overall Survival according to RECIST version 1.1
Time Frame:Study Day 1 up to time of death, assessed up to 24 months
Safety Issue:
Description:Based on Investigator review of radiographic imaging.
Measure:Time to Response (TTR) according to RECIST version 1.1
Time Frame:Study Day 1, assessed up to 24 months
Safety Issue:
Description:Based on Investigator review of radiographic imaging.
Measure:Disease Control Rate (DCR) according to RECIST version 1.1
Time Frame:Study Day 1, assessed up to 24 months
Safety Issue:
Description:Based on Investigator review of radiographic imaging.
Measure:Immunophenotyping of peripheral blood at various timepoints
Time Frame:Study Day 1, assessed up to 24 months
Safety Issue:
Description:Based on appropriate assay.
Measure:Immunophenotyping of tumor samples at various timepoints
Time Frame:Study Day 1, assessed up to 24 months
Safety Issue:
Description:Based on appropriate assay.
Measure:Assess presence of antibodies to THOR-707 at various timepoints
Time Frame:Study Day 1, assessed up to 24 months
Safety Issue:
Description:Based on appropriate assay.
Measure:Assess plasma concentration of THOR-707 at various timepoints
Time Frame:Study Day 1, assessed up to 24 months
Safety Issue:
Description:Based on appropriate assay.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Synthorx, Inc.

Trial Keywords

  • Synthorx
  • THOR-707
  • THOR 707
  • Interleukin 2
  • Interleukin-2
  • IL2
  • oncology
  • immuno-oncology
  • immunotherapy
  • IL-2

Last Updated

November 11, 2019