Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
ClinicalTrials.gov Identifier: NCT03815682
Recruitment Status : Recruiting
First Posted : January 24, 2019
Last Update Posted : April 16, 2019
Sponsor:
Information provided by (Responsible Party):
Torque Therapeutics Inc

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Solid Tumor Lymphoma Biological: TRQ15-01 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 24, 2018
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: TRQ15-01
Dose escalating TRQ15-01
Biological: TRQ15-01
Escalating dose levels




Primary Outcome Measures :
  1. Number of subjects with dose limiting toxicities [ Time Frame: First cyle of treatment (28 days) ]
    Safety of TRQ15-01

  2. Frequency of dose interruptions [ Time Frame: First cyle of treatment (28 days) ]
    Tolerability of TRQ15-01


Secondary Outcome Measures :
  1. Best overall response [ Time Frame: Baseline through approximately 6 months after TRQ15-01 last dose ]
    Per modified RECIST v1.1 (solid tumor) or Lugano classification (lymphoma)

  2. Progression free survival [ Time Frame: Baseline through approximately 6 months after TRQ15-01 last dose ]
    Per modified RECIST v1.1 (solid tumor) or Lugano classification (lymphoma)

  3. Maximum observed serum concentration of TRQ15-01 [ Time Frame: Baseline through approximately 1 year ]
    Maximum observed serum concentration of TRQ15-01

  4. Area under the serum concentration-time curve [ Time Frame: Baseline through approximately 1 year ]
    Area under the serum concentration-time curve

  5. Immunogenicity of TRQ015-01 [ Time Frame: Pre-dose through approximately 1 year after TRQ15-01 last dose ]
    Number of subject with anti-TRQ015-01 antibodies



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.


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

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 ClinicalTrials.gov identifier (NCT number): NCT03815682


Contacts
Layout table for location contacts
Contact: Marlyane Motta 786-564-1228 mmotta@torquetx.com
Contact: Becker Hewes, MD 617-777-4845 bhewes@torquetx.com

Locations
Layout table for location information
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Mihaela Cristea, MD       MCristea@coh.org   
UCSF Not yet recruiting
San Francisco, California, United States, 94143
Contact: Pamela Munster, MD       Pamela.Munster@ucsf.edu   
United States, Connecticut
Yale Not yet recruiting
New Haven, Connecticut, United States, 06511
Contact: Harriet Kluger, MD       harriet.kluger@yale.edu   
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Sarah Nikiforow, MD       Sarah_Nikiforow@DFCI.HARVARD.EDU   
United States, Michigan
Karmanos Cancer Institute Not yet recruiting
Detroit, Michigan, United States, 48201
Contact: Anthony Shields, MD       shieldsa@karmanos.org   
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55902
Contact: Aaron Mansfield, MD       Mansfield.Aaron@mayo.edu   
United States, New York
Mt. Sinail Medical Center Recruiting
New York, New York, United States, 10029
Contact: Karen Osman, MD       Keren.Osman@mountsinai.org   
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Erika Hamilton, MD         
United States, Texas
MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: George Blumenschein, MD       gblumens@mdanderson.org   
Sponsors and Collaborators
Torque Therapeutics Inc
Investigators
Layout table for investigator information
Study Director: Becker Hewes, MD Torque Therapeutics

Layout table for additonal information
Responsible Party: Torque Therapeutics Inc
ClinicalTrials.gov Identifier: NCT03815682     History of Changes
Other Study ID Numbers: TT-101
First Posted: January 24, 2019    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases