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

• ClinicalTrials.gov Identifier: NCT02904226
• Recruitment Status: Completed
• First Posted: September 16, 2016
• Results First Posted: September 9, 2021
• Last Update Posted: September 9, 2021
• Sponsor: Jounce Therapeutics, Inc.
• Information provided by (Responsible Party): Jounce Therapeutics, Inc.

Study Description

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 242 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
• Actual Primary Completion Date: July 1, 2020
• Actual Study Completion Date: July 1, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment Emergent Adverse Events (TEAE) [ Time Frame: 46.3 months ]
   Number of participants with an adverse event occurring from the time of informed consent until resolution or new therapy initiated or for 28 days post final dose if no new therapy is initiated
2. Number of Participants With Grade 5 (Fatal) Treatment Emergent Adverse Events (TEAE) [ Time Frame: 46.3 months ]
   Number of participants with Grade 5 (fatal) treatment emergent adverse events (TEAE) assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
3. Number of Participants With Grade 4 (Life Threatening) Treatment Emergent Adverse Events (TEAE) [ Time Frame: 46.3 months ]
   Number of participants with Grade 4 (life threatening) treatment emergent adverse events (TEAE) assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
4. Number of Participants With Grade 3 (Sever) Treatment Emergent Adverse Events (TEAE) [ Time Frame: 46.3 months ]
   Number of participants with Grade 3 (severe) treatment emergent adverse events (TEAE) assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03."
5. Number of Participants With Grade 2 (Moderate) Treatment Emergent Adverse Events (TEAE) [ Time Frame: 46.3 months ]
   Number of participants with Grade 2 (moderate) treatment emergent adverse events (TEAE) assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
6. Number of Participants With Grade 1 (Mild) Treatment Emergent Adverse Events (TEAE) [ Time Frame: 46.3 months ]
   Number of participants with Grade 1 (mild) treatment emergent adverse events (TEAE) assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
7. Number of Participants With Dose Limiting Toxicities [ Time Frame: 33 months ]
   Number of participants with at least one dose limiting toxicity (DLT)
8. Overall Response Rate [ Time Frame: 46.5 months ]
   Overall response rate (ORR) is defined as the proportion of subjects with a Best Overall Response characterized as either a Complete Response (CR) or Partial Response (PR) as defined by RECISTv1.1 guidelines based on investigator's review
9. Disease Control Rate [ Time Frame: 46.5 months ]
   Disease Control Rate: Percent Subjects with confirmed Complete Response + confirmed Partial Response + BoR of SD (or unconfirmed complete response or partial response lasting at least 53 days from the date of first dose)
10. Progression Free Survival [ Time Frame: 46.5 months ]
    Progression free survival, as determined by the Investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
11. 6 Month Landmark Progression Free Survival [ Time Frame: 46.5 months ]
    Percentage of patients that are progression free at 6 months, estimated by the Kaplan Meier method as the probability of being event-free at 6 months out of the entire 45.5-month primary study period. This method generates survival probability estimates across the Time Frame of the study using all data throughout the course of the trial.
12. 12 Month Landmark Progression Free Survival [ Time Frame: 46.5 months ]
    Percentage of patients that are progression free at 12 month, estimated by the Kaplan Meier method as the probability of being event-free at 12 months out of the entire 45.5-month primary study period. This method generates survival probability estimates across the Time Frame of the study using all data throughout the course of the trial.
13. Landmark Overall Survival at 6 Months [ Time Frame: 46.5 months ]
    Percentage of patients that are alive at 6 month, estimated by the Kaplan Meier method as the probability of being event-free at 6 months out of the entire 45.5-month primary study period. This method generates survival probability estimates across the Time Frame of the study using all data throughout the course of the trial.
14. Landmark Overall Survival at 12 Months [ Time Frame: 46.5 months ]
    Percentage of patients that are alive at 12 month, estimated by the Kaplan Meier method as the probability of being event-free at 12 months out of the entire 45.5-month primary study period. This method generates survival probability estimates across the Time Frame of the study using all data throughout the course of the trial.
15. Overall Survival [ Time Frame: 46.5 months ]
    The time from first dose date to the date of death for any cause

Eligibility Criteria

• 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

Contacts and Locations

Locations

United States, California

Stanford University School of Medicine

Palo Alto, California, United States, 94304

United States, Colorado

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States, 80218

United States, Connecticut

Yale New Haven Hospital

New Haven, Connecticut, United States, 06510

United States, District of Columbia

Georgetown Lombardi Comprehensive Cancer Center

Washington, District of Columbia, United States, 20007

United States, Illinois

The University of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, United States, 60637

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, New Jersey

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States, 07748

United States, New York

Memorial Sloan Kettering Westchester

Harrison, New York, United States, 10604

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

United States, Tennessee

Sarah Cannon Research Institute at TriStar Health

Nashville, Tennessee, United States, 37203

United States, Texas

The University of Texas - MD Anderson Cancer Center

Houston, Texas, United States, 77030

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, United States, 78229

United States, Washington

University of Washington

Seattle, Washington, United States, 98109

Sponsors and Collaborators

Jounce Therapeutics, Inc.

Investigators

• Study Director: Elizabeth Trehu, MD, FACP; Jounce Therapeutics, Inc.

  Study Documents (Full-Text)

Documents provided by Jounce Therapeutics, Inc.:

Study Protocol  [PDF] May 30, 2019

Statistical Analysis Plan  [PDF] March 4, 2020

More Information

• Responsible Party: Jounce Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02904226
• Other Study ID Numbers: JTX-2011-101
• First Posted: September 16, 2016
• Results First Posted: September 9, 2021
• Last Update Posted: September 9, 2021
• Last Verified: September 2021

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; Anti-CTLA-4; Ipilimumab; Pembrolizumab

Additional relevant MeSH terms:

Pembrolizumab; Nivolumab; Ipilimumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action