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JTX-2011 Alone and in Combination With Anti-PD-1 or Anti-CTLA-4 in Subjects With Advanced and/or Refractory Solid Tumors (ICONIC)

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ClinicalTrials.gov Identifier: NCT02904226
Recruitment Status : Recruiting
First Posted : September 16, 2016
Last Update Posted : June 28, 2018
Sponsor:
Information provided by (Responsible Party):
Jounce Therapeutics, Inc.

Brief Summary:
JTX-2011-101 is a Phase 1/2, open label, dose escalation and expansion clinical study of JTX-2011 alone and in combination with nivolumab, ipilimumab, or pembrolizumab in adult subjects with advanced and/or refractory solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy.

Condition or disease Intervention/treatment Phase
Cancer Drug: JTX-2011 Drug: Nivolumab Drug: Ipilimumab Drug: Pembrolizumab Phase 1 Phase 2

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 and in combination with nivolumab, ipilimumab, or pembrolizumab in adult subjects with advanced and/or refractory solid tumors. The study will include a dose escalation phase for single agent and the combination therapies, followed by an expansion phase in specified tumor types for single agent and the combination therapies.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 498 participants
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 and in Combination With Nivolumab, Ipilimumab, or Pembrolizumab in Adult Subjects With Advanced and/or Refractory Solid Tumor Malignancies
Actual Study Start Date : August 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part A (JTX-2011)
Phase 1 dose escalation and expansion of JTX-2011 by intravenous (IV) infusion
Drug: JTX-2011
Specified dose on specified 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 nivolumab by IV infusion
Drug: JTX-2011
Specified dose on specified days
Other Name: ICOS agonist monoclonal antibody

Drug: Nivolumab
Specified dose on specified days
Other Name: Opdivo

Experimental: Part C (JTX-2011)
Phase 2 expansion of JTX-2011 by IV infusion
Drug: JTX-2011
Specified dose on specified 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 nivolumab by IV infusion
Drug: JTX-2011
Specified dose on specified days
Other Name: ICOS agonist monoclonal antibody

Drug: Nivolumab
Specified dose on specified days
Other Name: Opdivo

Experimental: Part E (JTX-2011 + ipilimumab)
Phase 1 dose escalation of JTX-2011 by IV infusion in combination with ipilimumab by IV infusion
Drug: JTX-2011
Specified dose on specified days
Other Name: ICOS agonist monoclonal antibody

Drug: Ipilimumab
Specified dose on specified days
Other Name: Yervoy

Experimental: Part F (JTX-2011 + ipilimumab)
Phase 2 expansion of JTX-2011 by IV infusion in combination with ipilimumab by IV infusion
Drug: JTX-2011
Specified dose on specified days
Other Name: ICOS agonist monoclonal antibody

Drug: Ipilimumab
Specified dose on specified days
Other Name: Yervoy

Experimental: Part G (JTX-2011 + pembrolizumab)
Phase 1 dose escalation of JTX-2011 by IV infusion in combination with pembrolizumab by IV infusion
Drug: JTX-2011
Specified dose on specified days
Other Name: ICOS agonist monoclonal antibody

Drug: Pembrolizumab
Specified dose on specified days
Other Name: Keytruda

Experimental: Part H (JTX-2011 + pembrolizumab)
Phase 2 expansion of JTX-2011 by IV infusion in combination with pembrolizumab by IV infusion
Drug: JTX-2011
Specified dose on specified days
Other Name: ICOS agonist monoclonal antibody

Drug: Pembrolizumab
Specified dose on specified days
Other Name: Keytruda




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

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


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. 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. Evaluable or measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, and meet the requirements for the intended study cohort
  3. Male or Female ≥ 18 years of age
  4. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. Subjects with ECOG 2 may be considered for enrollment in Parts C, D, F, and H if approved by Medical Monitor
  5. Have a predicted life expectancy of ≥ 3 months
  6. Have laboratory values (obtained ≤ 28 days prior to first infusion day) in accordance with the study protocol
  7. If medical history of the following, case should be reviewed by the Medical Monitor: prior biliary tract disorders (as based on Hepatobiliary SOC high level terms of: obstructive bile duct disorders, hepatic vascular disorders, structural and other bile duct disorders) or portal hypertension and/or hepatic vascular disorders
  8. 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
  9. WOCBP and males with partners of child-bearing potential must agree to use adequate birth control throughout their participation and for 5 months following the last study treatment

Exclusion Criteria:

  1. Receiving concurrent anti-cancer treatment (excluding radiation therapy), either approved or investigational
  2. Have refused standard therapy
  3. Have received anti-cancer 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 subject (e.g. alopecia, Grade 2 neuropathy, hypo- or hyperthyroidism or other endocrinopathies that are well-controlled with hormone replacement) and are approved by the Medical Monitor.

    1. Have received biologic therapy, including immunotherapy, < 28 days prior to C1D1;
    2. Have received CAR-T therapy;
    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 undergone organ transplantation including allogeneic or autologous stem-cell transplantation, at any time;
  4. Have undergone a major surgery (excluding minor procedures, e.g. placement of vascular access, biopsy, etc.) < 6 months prior to the first day of study treatment, C1D1
  5. 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, ipilimumab, or pembrolizumab. Subjects who discontinued prior immunotherapies for immune-related adverse events that are well-controlled with appropriate treatment may be enrolled if approved by the Medical Monitor.
  6. 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 as well as a one-time dose of immunosuppressive agents used prophylactically for contrast allergies
  7. Have any active disease requiring systemic immunosuppressive treatment
  8. Have known severe intolerance to or life-threatening hypersensitivity reactions to humanized 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
  9. 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)
  10. Have current second malignancy at other sites, which requires treatment, or in the judgement of the Investigator, may require treatment within the next year. Concurrent malignancies that do not require treatment and are clinically stable are allowed. A past history of other malignancies is allowed as long as the subject is not receiving specific treatment other than hormonal therapy, and, in the judgement of the Investigator, is unlikely to have a recurrence.
  11. 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)
  12. Have received live vaccines within past 30 days (inactivated vaccines are allowed; seasonal vaccines should be up to date prior to first infusion day)
  13. Women who are pregnant or breastfeeding
  14. Have experienced symptomatic cardiac disease that is unresponsive to surgical or medical management
  15. 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

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: Kelly Mozzetta    720-754-2610      
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, District of Columbia, United States, 20007
Contact: Laura Macke, RN    202-687-2111      
United States, Illinois
The University of Chicago Medicine Comprehensive Cancer Center 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      
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Sue Gotthardt    617-975-7452      
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Kristina Kelley, RN    617-632-4876      
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Sarah Larson    314-747-1864      
United States, New Jersey
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Margaret Callahan, MD, PhD    646-888-4593      
United States, New York
Memorial Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Margaret Callahan, MD, PhD    646-888-4593      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Margaret Callahan, MD, PhD    646-888-4593      
United States, Tennessee
Sarah Cannon Research Institute at TriStar Health Recruiting
Nashville, Tennessee, United States, 37203
Contact: askSARAH    615-514-2401      
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    210-593-5256      
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98109
Contact: Heather Johnson, CCRC    206-606-7551      
Sponsors and Collaborators
Jounce Therapeutics, Inc.
Investigators
Study Director: Elizabeth Trehu, MD, FACP Jounce Therapeutics, Inc.

Responsible Party: Jounce Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02904226     History of Changes
Other Study ID Numbers: JTX-2011-101
First Posted: September 16, 2016    Key Record Dates
Last Update Posted: June 28, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Jounce Therapeutics, Inc.:
ICOS
ICOS agonist monoclonal antibody
JTX-2011
Anti-PD-1
Nivolumab
ICONIC
Immunotherapy
Immuno-oncology
Cancer
Solid Tumor
Dose Escalation
Dose Expansion
Anti-CTLA-4
Ipilimumab
Pembrolizumab

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