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Study of JTX 8064, as Monotherapy and in Combination With a PD-1 Inhibitor, in Adult Subjects With Advanced Refractory Solid Tumors

Sponsor
Jounce Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04669899
Collaborator
(none)
281
Enrollment
42
Locations
11
Arms
35.6
Anticipated Duration (Months)
6.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

JTX-8064-101 is a Phase 1/2, open label, dose escalation and dose expansion clinical study to determine the safety, tolerability, and recommended Phase 2 dose of JTX-8064 alone and in combination with a PD-1 inhibitor (PD-1i).

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

JTX-8064 is a humanized mAb designed to block the interaction of LILRB2 with its known ligands, endogenous major histocompatibility complex class I (MHC I) molecules. This is a Phase 1/2, first in human, open label, multicenter, dose escalation and dose expansion clinical trial to determine the safety, tolerability, MTD and RP2D of JTX-8064 when administered as a single agent and in combination with a PD-1i in adult subjects with advanced refractory solid tumor malignancies. Additionally, the study will seek to evaluate the pharmacokinetics and immunogenicity of JTX-8064, and preliminary efficacy of JTX-8064 as a monotherapy and in combination with a PD-1i.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
281 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1/2 First-in-Human (FIH) Study of Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2) Inhibitor Monoclonal Antibody (mAb) JTX-8064, as Monotherapy and in Combination With a Programmed Cell Death Receptor-1 (PD-1) Inhibitor, in Adult Subjects With Advanced Refractory Solid Tumor Malignancies
Actual Study Start Date :
Jan 12, 2021
Anticipated Primary Completion Date :
Sep 1, 2023
Anticipated Study Completion Date :
Jan 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Stage 1, Dose Escalation: JTX-8064 monotherapy dose escalation

Dose Escalation, Stage 1 JTX-8064 Monotherapy. Cohorts will enroll subjects with histologically or cytologically confirmed advanced/metastatic extracranial solid tumor malignancies

Drug: JTX-8064
Specified dose on specified days
Other Names:
  • Anti-LILRB2
  • Anti-ILT4

    		•
    Experimental: Stage 2, Dose Escalation: JTX-8064 in combination with pimivalimab

    Dose Escalation, Stage 2: JTX-8064 in combination with pimivalimab. Cohorts will enroll subjects with histologically or cytologically confirmed advanced/metastatic extracranial solid tumor malignancies

    Drug: JTX-8064
    Specified dose on specified days
    Other Names:
  • Anti-LILRB2
  • Anti-ILT4

    • Drug: pimivalimab
    Specified dose on specified days
    Other Names:
  • JTX-4014
  • Anti-PD-1

    		•
    Experimental: Stage 3 Expansion: JTX-8064 monotherapy (Ovarian)

    Cohort will enroll subjects with advanced/metastatic PD-1/PD-L1 (PD-(L)1)-naïve, platinum-resistant ovarian cancer

    Drug: JTX-8064
    Specified dose on specified days
    Other Names:
  • Anti-LILRB2
  • Anti-ILT4

    		•
    Experimental: Stage 4, Expansion: JTX-8064 in combination with pimivalimab (ccRCC)

    JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1i-experienced clear cell renal cell carcinoma (ccRCC)

    Drug: JTX-8064
    Specified dose on specified days
    Other Names:
  • Anti-LILRB2
  • Anti-ILT4

    • Drug: pimivalimab
    Specified dose on specified days
    Other Names:
  • JTX-4014
  • Anti-PD-1

    		•
    Experimental: Stage 4, Expansion: JTX-8064 in combination with pimivalimab (TNBC)

    JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1i-experienced triple negative breast cancer (TNBC)

    Drug: JTX-8064
    Specified dose on specified days
    Other Names:
  • Anti-LILRB2
  • Anti-ILT4

    • Drug: pimivalimab
    Specified dose on specified days
    Other Names:
  • JTX-4014
  • Anti-PD-1

    		•
    Experimental: Stage 4, Expansion: JTX-8064 in combination with pimivalimab (HNSCC)

    JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-naïve, PD-L1+ head and neck squamous cell carcinoma (HNSCC)

    Drug: JTX-8064
    Specified dose on specified days
    Other Names:
  • Anti-LILRB2
  • Anti-ILT4

    • Drug: pimivalimab
    Specified dose on specified days
    Other Names:
  • JTX-4014
  • Anti-PD-1

    		•
    Experimental: Stage 4, Expansion: JTX-8064 in combination with pimivalimab (Ovarian)

    JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-naïve, platinum resistant ovarian cancer

    Drug: JTX-8064
    Specified dose on specified days
    Other Names:
  • Anti-LILRB2
  • Anti-ILT4

    • Drug: pimivalimab
    Specified dose on specified days
    Other Names:
  • JTX-4014
  • Anti-PD-1

    		•
    Experimental: Stage 4, Expansion: JTX-8064 in combination with pimivalimab (NSCLC)

    JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-experienced non-small cell lung cancer (NSCLC)

    Drug: JTX-8064
    Specified dose on specified days
    Other Names:
  • Anti-LILRB2
  • Anti-ILT4

    • Drug: pimivalimab
    Specified dose on specified days
    Other Names:
  • JTX-4014
  • Anti-PD-1

    		•
    Experimental: Stage 4, Expansion: JTX-8064 in combination with pimivalimab (cSCC)

    JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-experienced cutaneous squamous cell carcinoma (cSCC)

    Drug: JTX-8064
    Specified dose on specified days
    Other Names:
  • Anti-LILRB2
  • Anti-ILT4

    • Drug: pimivalimab
    Specified dose on specified days
    Other Names:
  • JTX-4014
  • Anti-PD-1

    		•
    Experimental: Stage 4, Expansion: JTX-8064 in combination with pimivalimab (UPS & LPS)

    JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-naïve undifferentiated pleomorphic sarcoma (UPS) and liposarcoma (LPS)

    Drug: JTX-8064
    Specified dose on specified days
    Other Names:
  • Anti-LILRB2
  • Anti-ILT4

    • Drug: pimivalimab
    Specified dose on specified days
    Other Names:
  • JTX-4014
  • Anti-PD-1

    		•
    Experimental: Stage 4, Expansion: JTX-8064 in combination with pimivalimab (PD-(L)1i-experienced HNSCC)

    JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with PD-(L)1i-experienced HNSCC

    Drug: JTX-8064
    Specified dose on specified days
    Other Names:
  • Anti-LILRB2
  • Anti-ILT4

    • Drug: pimivalimab
    Specified dose on specified days
    Other Names:
  • JTX-4014
  • Anti-PD-1

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence and severity of dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuation due to adverse events (AEs). [up to 18 months]

      Evaluated using National Cancer Institute (NCI) Common Technology Criteria for Adverse Events (CTCAE) version 5.0

    2. Determination of a RP2D for JTX-8064 monotherapy and in combination with JTX-4014 or pembrolizumab [up to 12 months]

    Secondary Outcome Measures

    1. Cmax (the maximum observed concentration) for JTX-8064 when administered as monotherapy or in combination with a PD-1i [Cycle 1 through 12 (each cycle is 21 days)]

    2. Tmax (time of maximum observed concentration) for JTX-8064 when administered as monotherapy or in combination with a PD-1i [Cycle 1 through 12 (each cycle is 21 days)]

    3. Cmin for JTX-8064 when administered as monotherapy or in combination with a PD-1i [Cycle 1 through 12 (each cycle is 21 days)]

    4. AUClast (area under the concentration-time curve from time 0 to the last measurable concentration) for JTX-8064 when administered as monotherapy or in combination with a PD-1i [Cycle 1 and 3 (each cycle is 21 days)]

    5. Cmax for PD-1i in combination with JTX-8064 [Cycles 1 through 12 (each cycle is 21 days)]

    6. Tmax for PD-1i in combination with JTX-8064 [Cycles 1 through 12 (each cycle is 21 days)]

    7. Cmin for PD-1i in combination with JTX-8064 [Cycles 1 through 12 (each cycle is 21 days)]

    8. Incidence of ADAs to JTX-8064 and, as appropriate, to PD-1i [Baseline through Cycle 12 (each cycle is 21 days)]]

    9. Incidence of neutralizing antibodies (Nabs) to JTX-8064 and, as appropriate, to PD-1i [Baseline through Cycle 12 (each cycle is 21 days)]]

    10. For Stages 1 and 2: Receptor occupancy for LILRB2 on monocytes in whole blood [Baseline through Cycle 6 (each cycle is 21 days)]]

    11. For Stages 3 and 4: Preliminary efficacy endpoints: ORR (the proportion of subjects who have had a partial response, PR or complete response CR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [up to 36 months]

    12. For Stages 3 and 4: Preliminary efficacy endpoints: DCR (the proportion of subjects who have a PR, CR or stable disease SD), as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [up to 36 months]

    13. For Stages 3 and 4: Preliminary efficacy endpoints: Duration of response (DOR) (the time from documentation of tumor progression or death due to any cause, whichever comes first) [up to 36 months]

    14. For Stages 3 and 4: Preliminary efficacy endpoints: Percentage of subjects with tumor reduction at any time [up to 36 months]

    15. For Stages 3 and 4: Preliminary efficacy endpoints: Progression-free survival (PFS) (interval from start of treatment to the earlier of first documentation of disease progression or death from any cause) [up to 36 months]

    16. For Stages 3 and 4: Preliminary efficacy endpoints: Overall survival (OS) (the interval from start of treatment to death of any cause) [up to 36 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    1. Able and willing to participate and comply with all study requirements and provide signed and dated informed consent prior to initiation of any study procedures;

    2. Histologically or cytologically confirmed advanced/metastatic extracranial solid tumor malignancy.

    3. Stages 1 and 2: Subject must have received, have been intolerant to, have been ineligible for, or have declined all treatment known to confer clinical benefit with the exception of subjects enrolled in combination cohorts with a PD-1i, where a PD-1i is approved by the local regulatory agencies

    4. Stage 3: This stage may enroll subjects with the following cancers:

    • 3L/4L PD-(L)1-naïve, platinum-resistant ovarian cancer

    1. Stage 4: This stage may enroll subjects with the following cancers:

    • 2L/3L ccRCC. Subjects must have progressed on or after treatment with an anti-PD-(L)1 agent in their most recent prior line of therapy

    • 2L-4L TNBC. Subjects must have progressed on or after treatment with a prior anti-PD-(L)1 therapy

    • 1L, PD-(L)1-naïve, PD-L1+; combined positive score (CPS) ≥ 1% HNSCC

    • 3L/4L, PD-(L)1-naïve, platinum-resistant ovarian cancer

    • 2L/3L NSCLC; Subjects must have progressed on or after treatment with platinum-based chemotherapy and an anti-PD-(L)1-containing therapy. The anti-PD-(L)1 agent must have been a part of the most recent prior line of therapy. Subjects with EGFR mutations and ALK rearrangements will be excluded. Subjects with other targetable genomic aberrations for which FDA approved therapies exist must have received appropriate FDA-approved targeted therapy

    • 2L/3L cSCC; Subjects must have progressed on or after treatment with an anti-PD-(L)1 agent in their most recent prior line of therapy

    • 2L-4L PD-(L)1-naïve UPS and LPS

    • 2L/3L HNSCC. Subjects must have progressed on or after treatment with platinum-based chemotherapy and an anti-PD-(L)1-containing therapy. The anti-PD-(L)1 agent must have been a part of the most recent prior line of therapy.

    1. Measurable disease, according to the RECIST version 1.1, that has objectively progressed since (or on) previous treatment as assessed by the Investigator;

    2. ≥ 18 years of age;

    3. Eastern Cooperative Oncology Group performance status 0 or 1;

    4. Predicted life expectancy of ≥ 3 months;

    5. Have specified laboratory values (obtained ≤ 28 days prior to first dose) in accordance with the study protocol;

    6. For women of childbearing potential (WOCBP): negative serum pregnancy test during the Screening period and a negative urine pregnancy test up to 24 hours in advance of C1D1

    7. WOCBP and males whose partners are WOCBP must agree to use a highly effective method of birth control throughout their participation and for 5 months following the last study drug administration.

    Exclusion Criteria:

    1. Concurrent anticancer treatment, either FDA approved or investigational, for the cancer being evaluated in this study or for prior malignancies. A past history of other malignancies is allowed as long as the subject is not receiving treatment other than hormonal therapy and, in the judgment of the Investigator, is unlikely to have a recurrence. Of note, concurrent malignancies that do not require treatment and are clinically stable are allowed

    2. Prior infusion of JTX-8064, LILRB2, or ILT4-directed therapy;

    3. The therapies listed below within the specified timeframe:

    4. Immunotherapy or biologic therapy < 28 days prior to planned C1D1 or 5 half-lives, whichever is shorter

    5. Chemotherapy < 21 days prior to planned C1D1, or < 42 days for mitomycin or nitrosoureas or 5 half-lives, whichever is shorter

    6. Targeted small molecule therapy < 14 days or 5 half-lives, whichever is shorter, prior to planned C1D1

    7. Radiation therapy < 21 days prior to planned C1D1. Exception: Limited (e.g., pain palliation) radiation therapy is allowed prior to and during study drug administration as long as there are no acute toxicities, any AE due to prior radiation therapy has recovered to < Grade 2, and the radiation is not administered to a target lesion

    8. Symptomatic or uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation (brain metastases that are stable and asymptomatic after prior treatment will be allowed);

    9. Women who are pregnant or breastfeeding or who plan to become pregnant/breastfeed while on study; men who plan to father children during the study

    10. Live vaccines ≤ 30 days of C1D1

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama at Birmingham Birmingham Alabama United States 35249
    2 Arizona Clinical Research Center Tucson Arizona United States 85258
    3 University of California Irvine Costa Mesa California United States 92627
    4 City of Hope Duarte California United States 91010
    5 California Cancer Associates for Research & Excellence, INC La Jolla California United States 92037
    6 California Cancer Associates La Jolla California United States 92037
    7 University of California, San Diego La Jolla California United States 92093
    8 Cedars Sinai Los Angeles California United States 90048
    9 UC Irvine Medical Center Orange California United States 92868
    10 University of California, Davis Sacramento California United States 95817
    11 Yale University New Haven Connecticut United States 06519
    12 Georgetown University Washington District of Columbia United States 20057
    13 University of Florida Gainesville Florida United States 32610
    14 University of Miami - Sylvester Comprehensive Cancer Center Miami Florida United States 33136
    15 Adventist Health System/Sunbelt, Inc. Orlando Florida United States 32803
    16 Augusta Oncology Associates - Wheeler Road Augusta Georgia United States 30909
    17 Cancer Care Center of Decatur Decatur Illinois United States 62526
    18 University of Kentucky Chandler Medical Center (UKCMC) Lexington Kentucky United States 40536
    19 University of Michigan Ann Arbor Michigan United States 48109
    20 Barbara Ann Karmanos Cancer Center Detroit Michigan United States 48201
    21 Henry Ford Hospital Detroit Michigan United States 48202
    22 START Midwest -Cancer & Hematology Center of Western Michigan Grand Rapids Michigan United States 49546
    23 Regents of the University of Minnesota Minneapolis Minnesota United States 55455
    24 Weill Cornell New York New York United States 10021
    25 Mount Sinai New York New York United States 10029
    26 Montefiore Medical Center PRIME New York New York United States 10461
    27 Carolina BioOncology Huntersville North Carolina United States 28708
    28 Gabrail Cancer Center Canton Ohio United States 44718
    29 UC Health, LLC Cincinnati Ohio United States 45229
    30 Case Comprehensive Cancer Center Cleveland Ohio United States 44106
    31 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    32 Providence Portland Cancer Center Portland Oregon United States 97213
    33 Prisma Health Greenville South Carolina United States 29605
    34 Mary Crowley Cancer Research Dallas Texas United States 75230
    35 Oncology Consultants, P.A. Houston Texas United States 77024
    36 MD Anderson Houston Texas United States 77030
    37 Joe Arrington Cancer Research & Treatment Center Lubbock Texas United States 79410
    38 START Texas Accelerated Research Therapeutics San Antonio Texas United States 78229
    39 START Mountain Region West Valley City Utah United States 84119
    40 Seattle Cancer Care Alliance Seattle Washington United States 98331
    41 The Board of Regents of the University of Wisconsin Madison Wisconsin United States 53792
    42 Medical College of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • Jounce Therapeutics, Inc.

    Investigators

    • Study Director: Adam Y-Beltrán, M.D, Jounce Therapeutics, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Jounce Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT04669899
    Other Study ID Numbers:
    • JTX-8064-101
    First Posted:
    Dec 17, 2020
    Last Update Posted:
    Mar 10, 2022
    Last Verified:
    Feb 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Jounce Therapeutics, Inc.
    JTX-8064
    LILRB2
    ILT-4
    PD-1
    JTX-4014
    Immunotherapy
    Immuno-oncology
    Solid tumor Malignancies
    Dose escalation
    INNATE
    Monotherapy
    Combination Therapy
    Antineoplastic Agents
    Immunological

    Study Results

    No Results Posted as of Mar 10, 2022