Clinical Trials /

TRQ15-01 in Patients With Relapsed/Refractory Solid Tumors and Lymphomas

NCT03815682

Description:

The purpose of this study is to assess the safety and tolerability of escalating doses of TRQ15-01 in patients with relapsed/refractory/metastatic or locally-advanced solid tumors and lymphomas.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Lymphoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Sarcoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: TRQ15-01 in Patients With Relapsed/Refractory Solid Tumors and Lymphomas
  • Official Title: A Phase 1/1b Open-Label Multi-Center Study to Characterize the Safety and Tolerability of TRQ15-01 in Patients With Relapsed/Refractory Solid Tumors and Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: TT-101
  • NCT ID: NCT03815682

Conditions

  • Solid Tumor
  • Lymphoma

Interventions

DrugSynonymsArms
TRQ15-01TRQ15-01

Purpose

The purpose of this study is to assess the safety and tolerability of escalating doses of TRQ15-01 in patients with relapsed/refractory/metastatic or locally-advanced solid tumors and lymphomas.

Detailed Description

      This is a first-in-human, Phase 1, open-label, multicenter, dose escalation study designed to
      determine the safety and tolerability of TRQ15-01 in patients with relapsed/refractory or
      locally advanced solid tumors or lymphomas. The study will include 2 dosing periods: a Dose
      Escalation Phase followed by an Expansion Phase.
    

Trial Arms

NameTypeDescriptionInterventions
TRQ15-01ExperimentalDose escalating TRQ15-01
  • TRQ15-01

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent must be obtained prior to any study procedures.

          2. Age ≥ 18 years (or ≥ 16 years at Children's National Medical Center).

          3. Histologically- or cytologically-confirmed relapsed/refractory metastatic or
             locally-advanced solid tumor or lymphoma whose disease has progressed despite all
             appropriate curative or life-prolonging treatments, are intolerant to these therapies
             or have refused standard treatment.

             Note: Cohort enrollment may be limited to potentially immune-responsive tumor types
             meeting the above criterion during the first approximately 2 weeks of the enrollment
             period of each cohort due to their potential to respond to and activate TRQ15-01:

               -  Non-small cell lung cancer

               -  Melanoma

               -  Clear cell cancer of the kidney

               -  Head and neck squamous cell cancer

               -  Urothelial cancer

               -  Lymphoma

               -  Sarcomas

               -  Ovarian Cancer

               -  Other tumors determined likely to be immunogenic based upon emerging data as
                  discussed during escalation teleconferences

          4. Patients with measurable disease (at least one measurable lesion, at least 1.0 cm in
             diameter), documented within 10 weeks of their projected C1D1 visit, as determined by
             RECIST v1.1 for patients with solid tumors or Lugano classification or if nodal, at
             least 1.5cm or greater in the short axis dimension for patients with lymphoma.

          5. ECOG Performance Status ≤ 1.

          6. Patient must have a site of disease amenable to biopsy and be a candidate for tumor
             biopsy according to the treating institution's guidelines. Patient must be willing to
             undergo tumor biopsies, one new tumor biopsy during screening period 2 or provide a
             suitable archival sample for assessment of the tumor microenvironment, and during
             therapy on this study.

        Exclusion Criteria:

          1. Previously identified hypersensitivity to components of TRQ15-01 or excipients.

          2. Patients with T-cell lymphomas or small lymphocytic lymphoma.

          3. Presence of active central nervous system (CNS) disease unless the CNS metastases have
             been previously treated, the patient is clinically stable, asymptomatic and the
             patient has discontinued corticosteroids for at least 4 weeks prior to enrollment.

          4. Patient having out of range laboratory values defined as:

               -  Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 40
                  mL/min

               -  Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are
                  excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN

               -  Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) > 3 x ULN,
                  except for patients that have tumor involvement of the liver, who are excluded if
                  ALT > 5 x ULN

               -  Absolute neutrophil count ≤ 1.0 x 109/L

                    -  0.5 x 109/L and increasing following prior myelosuppressive treatment will
                       be eligible

               -  Absolute lymphocyte count ≤ 1.0 x 109/L

               -  Platelet count ≤ 75 x 109/L absent platelet transfusion for 2 weeks

               -  Hemoglobin (Hgb) ≤ 9 g/dL absent RBC transfusion for 2 weeks

                    -  8 g/dL and increasing following prior myelosuppressive treatment will be
                       eligible

               -  Potassium, magnesium, calcium or phosphate abnormality > CTCAE grade 1 despite
                  appropriate oral replacement therapy

               -  Serum triglycerides > 500 mg/dL due to potential interference with cell
                  separation methods

          5. Impaired cardiac function or clinically significant cardiac disease, including any of
             the following:

               -  Clinically significant and/or uncontrolled heart disease such as congestive heart
                  failure requiring treatment (NYHA grade ≥ 2), uncontrolled hypertension or
                  clinically significant arrhythmia

               -  Acute myocardial infarction or unstable angina pectoris < 6 months prior to study
                  entry

          6. Patients with active, known or suspected autoimmune disease. Patients with vitiligo,
             type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition only
             requiring hormone replacement, psoriasis not requiring systemic treatment, or
             conditions not expected to recur in the absence of an external trigger are permitted
             to enroll.

          7. Known (testing not required) Human Immunodeficiency Virus (HIV), active Hepatitis B
             (HBV) or active Hepatitis C (HCV) virus.

          8. Malignant disease, other than that being treated in this study expected to interfere
             with the assessment of efficacy in the opinion of the investigator.

          9. Active infection requiring systemic antibiotic therapy.

         10. Patients requiring chronic treatment with systemic steroid therapy, other than
             replacement dose steroids in the setting of adrenal insufficiency. Topical, inhaled,
             nasal, or ophthalmic steroids are allowed.

         11. Patients receiving systemic treatment with any immunosuppressive medication.

         12. Use of any live vaccines against infectious diseases (e.g. influenza, varicella,
             pneumococcus) within 4 weeks of initiation of study treatment.

         13. Major surgery within 4 weeks of the first dose of study treatment (mediastinoscopy,
             insertion of a central venous access device, and insertion of a feeding tube are not
             considered major surgery).

         14. Participation in an interventional, investigational study within 2 weeks of the first
             dose of study treatment.

         15. Presence of ≥ CTCAE grade 2 toxicity from prior therapy (except alopecia, peripheral
             neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer
             treatment.

         16. Initiation of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF,
             M-CSF) ≤2 weeks prior to start of study drug. An erythroid stimulating agent is
             allowed as long as it was initiated at least 2 weeks prior to the first dose of study
             treatment.

         17. An unresolved adverse event (must be ≤ Grade 1 or the patient's baseline).

         18. Prior treatment with CAR T-cell therapy.

         19. Prior allogeneic stem cell transplant.

         20. Patients who were required to discontinue PD-1/PDL-1, CTLA-4 or other immunomodulatory
             antibodies due to ≥ grade 3 irAE may be included following discussion with the
             sponsor.

         21. Patients with a history of > 3 lines of chemotherapy in the metastatic setting may be
             eligible for enrollment following discussion with the sponsor.

         22. Clinical or radiological disease progression (excluding pseudoprogression) on
             PD-1/PDL-1, CTLA-4 inhibitors within 8 weeks of the initial dose of the prior
             treatment may only be enrolled following discussion with the sponsor to account for
             manufacturing time.

         23. Prior therapy with PD-1/PDL-1, CTLA-4 or other immunomodulatory antibodies inhibitors:

               1. ≤2 weeks prior to the apheresis procedure

               2. ≤4 weeks prior to the first dose of study treatment

         24. Systemic anti-cancer therapy within 5 half-lives or 2 weeks; whichever occurs first,
             of the first dose of study treatment.

             a. Systemic cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and
             nitrosoureas, ≤ 6 weeks prior to the first dose of study treatment

         25. Any medical condition that would, in the investigator's judgment, prevent the
             patient's participation in the clinical study due to safety concerns, compliance with
             clinical study procedures or interpretation of study results.

         26. Lactating or pregnant women confirmed by a positive hCG laboratory test.

         27. Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they are using highly effective methods of contraception
             during study treatment and for 30 days after the last dose of study treatment. Highly
             effective contraception methods include:

               1. Female sterilization, total hysterectomy or tubal ligation at least 6 weeks
                  before taking study treatment

               2. Male sterilization (at least 6 months prior to screening). For female patients on
                  the study the vasectomized male partner should be the sole partner for that
                  patient

               3. Use of oral (estrogen and progesterone), injected or implanted combined hormonal
                  methods of contraception or placement of an intrauterine device (IUD) or
                  intrauterine system (IUS) or other forms of hormonal contraception that have
                  comparable efficacy (failure rate <1%), for example hormone vaginal ring or
                  transdermal hormone contraception In case of use of oral contraception women
                  should have been stable on the same pill for a minimum of 3 months before taking
                  study treatment.

             Women are considered post-menopausal and not of child bearing potential if they have
             had 12 months of natural amenorrhea with an appropriate clinical profile or have had
             surgical bilateral oophorectomy or tubal ligation at least 6 weeks prior to the first
             dose of study treatment.

         28. Sexually active males unless they use a condom during intercourse while taking drug
             and for 30 days after stopping study treatment and should not father a child in this
             period.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects with dose limiting toxicities
Time Frame:First cyle of treatment (28 days)
Safety Issue:
Description:Safety of TRQ15-01

Secondary Outcome Measures

Measure:Best overall response
Time Frame:Baseline through approximately 6 months after TRQ15-01 last dose
Safety Issue:
Description:Per modified RECIST v1.1 (solid tumor) or Lugano classification (lymphoma)
Measure:Progression free survival
Time Frame:Baseline through approximately 6 months after TRQ15-01 last dose
Safety Issue:
Description:Per modified RECIST v1.1 (solid tumor) or Lugano classification (lymphoma)
Measure:Maximum observed serum concentration of TRQ15-01
Time Frame:Baseline through approximately 1 year
Safety Issue:
Description:Maximum observed serum concentration of TRQ15-01
Measure:Area under the serum concentration-time curve
Time Frame:Baseline through approximately 1 year
Safety Issue:
Description:Area under the serum concentration-time curve
Measure:Immunogenicity of TRQ015-01
Time Frame:Pre-dose through approximately 1 year after TRQ15-01 last dose
Safety Issue:
Description:Number of subject with anti-TRQ015-01 antibodies

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Torque Therapeutics Inc

Last Updated

September 25, 2019