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Trial record 1 of 1 for:    jtx-2011
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Dose Escalation and Expansion of JTX-2011 Alone or in Combination With Anti-PD-1 in Subjects With Advanced Solid Tumors (ICONIC)

This study is currently recruiting participants.
Verified June 2017 by Jounce Therapeutics, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02904226
First Posted: September 16, 2016
Last Update Posted: June 6, 2017
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.
Information provided by (Responsible Party):
Jounce Therapeutics, Inc.
  Purpose
JTX-2011-101 is a Phase 1/2, open label, dose escalation and expansion clinical study of JTX-2011 alone or in combination with a fixed dose of nivolumab in subjects with advanced solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

Condition Intervention Phase
Cancer Drug: JTX-2011 Drug: nivolumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/2 Multicenter Trial of ICOS Agonist Monoclonal Antibody (mAb) JTX-2011 Alone or in Combination With Nivolumab in Adult Subjects With Advanced Refractory Solid Tumor Malignancies

Resource links provided by NLM:


Further study details as provided by Jounce Therapeutics, Inc.:

Primary Outcome Measures:
  • % subjects with adverse events (AEs) [ Time Frame: 26 months ]
  • % subjects with serious adverse events (SAEs) [ Time Frame: 26 months ]
  • % subjects with dose-limiting toxicities (DLTs) [ Time Frame: 20 months ]
  • % subjects with changes from baseline in pro-inflammatory cytokines [ Time Frame: 26 months ]
  • % subjects with anti-drug antibodies (ADA) to JTX-2011 [ Time Frame: 26 months ]
  • % subjects with ADA to nivolumab [ Time Frame: 26 months ]
  • % subjects with clinically significant change from baseline in clinical laboratory tests [ Time Frame: 26 months ]
  • Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JTX-2011 [ Time Frame: 26 months ]
  • % subjects with overall response (OR) [ Time Frame: 26 months ]
  • % subjects with complete response (CR) [ Time Frame: 26 months ]
  • Median duration of response (DOR) [ Time Frame: 26 months ]
  • Median progression free survival (PFS) [ Time Frame: 26 months ]
  • Median overall survival (OS) [ Time Frame: 26 months ]
  • Landmark overall survival (OS) [ Time Frame: 26 months ]

Secondary Outcome Measures:
  • Maximum measured concentration in serum (Cmax) [ Time Frame: 26 months ]
  • Minimum measured concentration in serum (Cmin) [ Time Frame: 26 months ]
  • Time from dosing to maximum measured concentration (tmax) [ Time Frame: 26 months ]
  • Area under the serum concentration-time curve (AUC) [ Time Frame: 26 months ]
  • Terminal half-life (t1/2) [ Time Frame: 26 months ]
  • Mean residence time (MRT) [ Time Frame: 26 months ]
  • Total clearance of the analyte in serum (CL) [ Time Frame: 26 months ]
  • Apparent volume of distribution during specific time points [ Time Frame: 26 months ]
  • % target engagement [ Time Frame: 26 months ]
  • Area under the effect-time curve (AUEC) of the pharmacodynamics marker in serum [ Time Frame: 26 months ]

Estimated Enrollment: 282
Study Start Date: August 2016
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A (JTX-2011)
Phase 1 dose escalation and expansion of JTX-2011 by intravenous (IV) infusion every 21 days in subjects with advanced refractory solid tumors
Drug: JTX-2011
JTX-2011 administered as a one hour IV infusion every 21 days
Other Name: ICOS agonist monoclonal antibody
Experimental: Part B (JTX-2011 + nivolumab)
Phase 1 dose escalation and expansion of JTX-2011 by IV infusion in combination with a fixed dose of nivolumab by IV infusion every 21 days in subjects with advanced refractory solid tumors
Drug: JTX-2011
JTX-2011 administered as a one hour IV infusion every 21 days
Other Name: ICOS agonist monoclonal antibody
Drug: nivolumab
Nivolumab 240 mg administered as a one hour IV infusion every 21 days
Other Name: OPDIVO
Experimental: Part C (JTX-2011)
Phase 2 expansion of JTX-2011 by IV infusion every 21 days in subjects with advanced refractory solid tumors
Drug: JTX-2011
JTX-2011 administered as a one hour IV infusion every 21 days
Other Name: ICOS agonist monoclonal antibody
Experimental: Part D (JTX-2011 + nivolumab)
Phase 2 expansion of JTX-2011 by IV infusion in combination with a fixed dose of nivolumab by IV infusion every 21 days in subjects with specific advanced refractory solid tumors
Drug: JTX-2011
JTX-2011 administered as a one hour IV infusion every 21 days
Other Name: ICOS agonist monoclonal antibody
Drug: nivolumab
Nivolumab 240 mg administered as a one hour IV infusion every 21 days
Other Name: OPDIVO

Detailed Description:
JTX-2011 is an agonist monoclonal antibody that specifically binds to the Inducible CO-Stimulator of T cells (ICOS) to generate an anti-tumor immune response. This is a Phase 1/2, open label, multicenter, dose escalation and expansion, first-in-human (FIH) clinical study to evaluate the safety and tolerability, PK, PD, and preliminary efficacy of the ICOS agonist monoclonal antibody JTX-2011 alone or in combination with a fixed dose of nivolumab in adult subjects with advanced refractory solid tumors. The study will be conducted in four parts: single agent (Part A) and combination therapy (Part B) dose escalation, and expansion cohorts of single agent (Part C) and combination therapy (Part D).
  Eligibility

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.


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

Inclusion Criteria:

  1. Must be willing and able to participate and comply with all trial requirements and able to provide signed and dated informed consent prior to initiation of any trial procedures;
  2. Have histologically or cytologically confirmed cancer that is recurrent, metastatic, or persistent after at least one line of therapy and with no further standard treatment options; evaluable or measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, with at least one measurable lesion that has objectively progressed since (or on) previous treatment (unless subject has refused standard of care treatment), as assessed by enrolling physician; and meet the requirements for the intended study cohort
  3. All subjects in Parts A and B must have available and consent to provide archival tumor tissue
  4. All subjects in Parts A and B Expansion must have a tumor lesion that can be biopsied at acceptable risk and must agree to both a fresh biopsy between screening and Cycle 1 Day 1 (C1D1) and a second biopsy after completion of two cycles of study treatment
  5. All subjects in Parts C and D must have available and consent to provide archival tumor tissue, have a lesion that can be biopsied at acceptable clinical risk (as judged by the investigator), and agree to a fresh biopsy between screening and C1D1. If the tumor site to be biopsied was previously irradiated or is the target lesion for response assessment, it must be at least 2 cm and have progressed
  6. Male or Female ≥ 18 years of age
  7. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. Subjects with PS 2 may be considered for enrollment in Parts C and D, if approved by medical monitor
  8. Have a predicted life expectancy of ≥ 3 months
  9. Have the following laboratory values (obtained ≤ 28 days prior to first infusion day):

    1. Serum creatinine <1.5 × ULN or if higher than normal range, calculated creatinine clearance (CrCl) must be ≥ 50 mL/min/1.73 m2 (e.g., by Cockroft-Gault formula); actual body weight must be used for CrCl unless BMI >30 kg/m2 then lean body weight must be used
    2. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) unless prior history of Gilbert's syndrome
    3. Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN, or ≤ 5 × ULN if due to liver involvement by tumor
    4. Hemoglobin ≥ 9.0 g/dL
    5. Platelets ≥ 100 × 109 cells/L
    6. Absolute neutrophil count (ANC) ≥ 1.5 ×109 cells/L (without the use of hematopoietic growth factors). Subjects with lower ANC may be enrolled if not the result of prior therapy, if approved by medical monitor
  10. Have a corrected QT interval (QTc) < 470ms for females and < 450ms for males (as calculated by the Fridericia correction formula)
  11. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to administration of each dose of JTX-2011
  12. Women of child-bearing potential (WOCBP) and males with partners of child-bearing potential must agree to use adequate birth control throughout their participation and for 3 months following the last study treatment

Exclusion Criteria:

  1. Receiving concurrent anticancer treatment (including radiation therapy), either approved or investigational
  2. Have refused standard therapy
  3. Have received the therapies listed below within the specified timeframe, or who have ongoing toxicity from prior therapy > Grade 1 according to the Common Terminology for Adverse Events (CTCAE). Exceptions to this are: > Grade 1 toxicities which in the opinion of the investigator should not exclude the patient (e.g. alopecia, Grade 2 neuropathy, hypo- or hyper-thyroidism or other endocrinopathies that are well-controlled with hormone replacement) and are approved by the medical monitor. Major surgery (excluding minor procedures, e.g. placement of vascular access) < 6 months prior to the first day of study treatment, C1D1

    1. Have undergone a major surgery (excluding minor procedures, e.g. placement of vascular access) < 6 months prior to the first day of study treatment, C1D1
    2. Have received biologic therapy, including immunotherapy, < 28 days prior to C1D1
    3. Have received chemotherapy < 21 days prior to C1D1, or < 42 days for mitomycin or nitrosoureas
    4. Have received targeted small molecule therapy < 14 days prior to C1D1
    5. Have received hormonal therapy < 14 days prior to C1D1 (Bisphosphonates are permitted provided treatment was initiated ≥ 14 days prior to C1D1)
    6. Have received radiation therapy < 21 days prior to C1D1
    7. Have undergone organ transplantation including allogeneic or autologous stem-cell transplantation, at any time
  4. Have a history of intolerance, hypersensitivity, or treatment discontinuation due to severe immune adverse events on prior immunotherapy, or documented presence of neutralizing anti-drug antibody to nivolumab (Parts B and D). Subjects who discontinued prior immunotherapies for immune related adverse events that are well-controlled with appropriate treatment, and, in the opinion of the investigator, may be enrolled if approved by the medical monitor
  5. Have a diagnosis of immunodeficiency, either primary or acquired, or treatment with systemic steroids or any other form of immunosuppressive therapy within 7 days prior to C1D1. Exception: inhaled or topical steroids and adrenal replacement doses are permitted in the absence of active autoimmune disease
  6. Have an active or prior history of autoimmune disease. Exception: subjects with type 1 diabetes, vitiligo, hypo- or hyperthyroid disease, or autoimmune alopecia not requiring immunosuppressive treatment
  7. Have known severe intolerance to or hypersensitivity reactions to monoclonal antibodies or intravenous immunoglobulin preparations; any history of anaphylaxis; prior history of human anti-human antibody response; known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
  8. Are symptomatic or have uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation (brain metastases that are stable and asymptomatic, either treated or untreated, will be allowed)
  9. Have current second malignancy at other sites (exceptions: adequately treated in situ carcinoma (e.g., cervical), non-melanoma skin cancer, bilateral synchronous discordant breast cancer, or indolent prostate cancer under observation). A past history of other malignancies is allowed as long as subject has been free of recurrence for ≥ 2 years, or if the subject has been treated with curative intent within the past 2 years and, in the opinion of the investigator, is unlikely to have a recurrence
  10. Have active and clinically relevant bacterial, fungal, or viral infection, including known Hepatitis A, B, or C or human immunodeficiency virus (HIV) (testing not required)
  11. Have received live vaccines within past 30 days (inactivated vaccines are allowed; seasonal vaccines should be up to date prior to first infusion day)
  12. Women who are pregnant or breastfeeding
  13. Have experienced the occurrence of any of the following within 1 year prior to C1D1: myocardial infarction, uncontrolled angina, coronary artery bypass graft, symptomatic congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, cardiac amyloidosis, cerebrovascular accident, or transient ischemic attack
  14. Have any medical or social condition that, in the opinion of the investigator, might place a subject at increased risk, affect compliance, or confound safety or other clinical trial data interpretation
  Contacts and Locations
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): NCT02904226


Contacts
Contact: Manny Lazaro ICONIC@jouncetx.com

Locations
United States, California
Stanford University School of Medicine Recruiting
Palo Alto, California, United States, 94304
Contact: Feriel Buchholz    650-721-4090      
United States, Colorado
Sarah Cannon Research Institute at HealthONE Recruiting
Denver, Colorado, United States, 80218
Contact: Lori Hannan    720-754-4649      
United States, Connecticut
Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Contact: Caroline Hotchkiss, MPH, CCRP    203-737-5228      
United States, District of Columbia
Georgetown Lombardi Comprehensive Cancer Center Recruiting
Washington, D.C., District of Columbia, United States, 20007
Contact: Bridget Haley    202-687-6871      
United States, Illinois
The University of Chicago Medicine Comprehensive Cancer Center Not yet recruiting
Chicago, Illinois, United States, 60637
Contact: Sara Kochanny    773-702-2336      
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Justin Gainor    617-724-4000      
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Sarah Larson    314-747-1864      
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Margaret Callahan, MD, PhD    800-525-2225      
United States, Tennessee
Sarah Cannon Research Institute at TriStar Health Recruiting
Nashville, Tennessee, United States, 37203
Contact: askSARAH    877-691-7274      
United States, Texas
The University of Texas - MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Timothy Yap    877-632-6789      
South Texas Accelerated Research Therapeutics, LLC Recruiting
San Antonio, Texas, United States, 78229
Contact: Isabel Jimenez, RN, MSN    210-593-5252      
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98109
Contact: Heather Johnson, CCRC    206-288-7551      
Sponsors and Collaborators
Jounce Therapeutics, Inc.
Investigators
Study Director: Elizabeth Trehu, MD, FACP Jounce Therapeutics, Inc.
  More Information

Responsible Party: Jounce Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02904226     History of Changes
Other Study ID Numbers: JTX-2011-101
First Submitted: September 7, 2016
First Posted: September 16, 2016
Last Update Posted: June 6, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Jounce Therapeutics, Inc.:
JTX-2011
ICOS
ICOS agonist monoclonal antibody
Anti-PD-1
Nivolumab
ICONIC
Immunotherapy
Immuno-oncology
Cancer
Solid Tumor
Dose Escalation
Dose Expansion

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Nivolumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents