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

NCT02904226 | Completed Phase 1 Results

• 1 other identifier: JTX-2011-101
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 16

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.

Conditions

Cancer

Keywords

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

Outcome Measures

Primary Outcomes (15)

• Number of Participants With Treatment Emergent Adverse Events (TEAE)

  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

  46.3 months

• Number of Participants With Grade 5 (Fatal) Treatment Emergent Adverse Events (TEAE)

  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.

  46.3 months

• Number of Participants With Grade 4 (Life Threatening) Treatment Emergent Adverse Events (TEAE)

  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.

  46.3 months

• Number of Participants With Grade 3 (Sever) Treatment Emergent Adverse Events (TEAE)

  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."

  46.3 months

• Number of Participants With Grade 2 (Moderate) Treatment Emergent Adverse Events (TEAE)

  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

  46.3 months

• Number of Participants With Grade 1 (Mild) Treatment Emergent Adverse Events (TEAE)

  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

  46.3 months

• Number of Participants With Dose Limiting Toxicities

  Number of participants with at least one dose limiting toxicity (DLT)

  33 months

• Overall Response Rate

  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

  46.5 months

• Disease Control Rate

  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)

  46.5 months

• Progression Free Survival

  Progression free survival, as determined by the Investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  46.5 months

• 6 Month Landmark Progression Free Survival

  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.

  46.5 months

• 12 Month Landmark Progression Free Survival

  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.

  46.5 months

• Landmark Overall Survival at 6 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.

  46.5 months

• Landmark Overall Survival at 12 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.

  46.5 months

• Overall Survival

  The time from first dose date to the date of death for any cause

  46.5 months

Study Arms (8)

Part A (JTX-2011)

EXPERIMENTAL

Phase 1 dose escalation and expansion of JTX-2011 by intravenous (IV) infusion

Drug: JTX-2011

Part B (JTX-2011 + nivolumab)

EXPERIMENTAL

Phase 1 dose escalation and expansion of JTX-2011 by IV infusion in combination with nivolumab by IV infusion

Drug: JTX-2011; Drug: Nivolumab

Part C (JTX-2011)

EXPERIMENTAL

Phase 2 expansion of JTX-2011 by IV infusion

Drug: JTX-2011

Part D (JTX-2011 + nivolumab)

EXPERIMENTAL

Phase 2 expansion of JTX-2011 by IV infusion in combination with nivolumab by IV infusion

Drug: JTX-2011; Drug: Nivolumab

Part E (JTX-2011 + ipilimumab)

EXPERIMENTAL

Phase 1 dose escalation of JTX-2011 by IV infusion in combination with ipilimumab by IV infusion

Drug: JTX-2011; Drug: Ipilimumab

Part F (JTX-2011 + ipilimumab)

EXPERIMENTAL

Phase 2 expansion of JTX-2011 by IV infusion in combination with ipilimumab by IV infusion

Drug: JTX-2011; Drug: Ipilimumab

Part G (JTX-2011 + pembrolizumab)

EXPERIMENTAL

Phase 1 dose escalation of JTX-2011 by IV infusion in combination with pembrolizumab by IV infusion

Drug: JTX-2011; Drug: Pembrolizumab

Part H (JTX-2011 + pembrolizumab)

EXPERIMENTAL

Phase 2 expansion of JTX-2011 by IV infusion in combination with pembrolizumab by IV infusion

Drug: JTX-2011; Drug: Pembrolizumab

Interventions

JTX-2011 DRUG

Specified dose on specified days

Also known as: ICOS agonist monoclonal antibody

Part A (JTX-2011); Part B (JTX-2011 + nivolumab); Part C (JTX-2011); Part D (JTX-2011 + nivolumab); Part E (JTX-2011 + ipilimumab); Part F (JTX-2011 + ipilimumab); Part G (JTX-2011 + pembrolizumab); Part H (JTX-2011 + pembrolizumab)

Nivolumab DRUG

Specified dose on specified days

Also known as: Opdivo

Part B (JTX-2011 + nivolumab); Part D (JTX-2011 + nivolumab)

Ipilimumab DRUG

Specified dose on specified days

Also known as: Yervoy

Part E (JTX-2011 + ipilimumab); Part F (JTX-2011 + ipilimumab)

Pembrolizumab DRUG

Specified dose on specified days

Also known as: Keytruda

Part G (JTX-2011 + pembrolizumab); Part H (JTX-2011 + pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• Male or Female ≥ 18 years of age
• 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
• Have a predicted life expectancy of ≥ 3 months
• Have laboratory values (obtained ≤ 28 days prior to first infusion day) in accordance with the study protocol
• 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
• 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
• 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

You may not qualify if:

• Receiving concurrent anti-cancer treatment (excluding radiation therapy), either approved or investigational
• Have refused standard therapy
• 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.
• Have received biologic therapy, including immunotherapy, \< 28 days prior to C1D1;
• Have received CAR-T therapy;
• Have received chemotherapy \< 21 days prior to C1D1, or \< 42 days for mitomycin or nitrosoureas;
• Have received targeted small molecule therapy \< 14 days prior to C1D1;
• Have undergone organ transplantation including allogeneic or autologous stem-cell transplantation, at any time;
• 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
• 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.
• 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
• Have any active disease requiring systemic immunosuppressive treatment
• 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
• 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)
• 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.

Sponsors & Collaborators

• Jounce Therapeutics, Inc.: lead

Study Sites (16)

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

The University of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute at TriStar Health

Nashville, Tennessee, 37203, United States

Location

The University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Nivolumab; Ipilimumab; pembrolizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Stew Kroll, Chief Development Officer
• Organization: Jounce Therapeutics, Inc.

skroll@jouncetx.com

(650) 576-9679

Study Officials

• Stew Kroll

  Jounce Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2016
• First Posted: September 16, 2016
• Study Start: August 1, 2016
• Primary Completion: July 1, 2020
• Study Completion: July 1, 2020
• Last Updated: July 3, 2023
• Results First Posted: September 9, 2021

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)