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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

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ClinicalTrials.gov Identifier: NCT04669899
Recruitment Status : Recruiting
First Posted : December 17, 2020
Last Update Posted : July 23, 2021
Sponsor:
Information provided by (Responsible Party):
Jounce Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE December 4, 2020
First Posted Date  ICMJE December 17, 2020
Last Update Posted Date July 23, 2021
Actual Study Start Date  ICMJE January 12, 2021
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 9, 2020)
  • Incidence and severity of dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuation due to adverse events (AEs). [ Time Frame: up to 18 months ]
    Evaluated using National Cancer Institute (NCI) Common Technology Criteria for Adverse Events (CTCAE) version 5.0
  • Determination of a RP2D for JTX-8064 monotherapy and in combination with JTX-4014 or pembrolizumab [ Time Frame: up to 12 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 19, 2021)
  • Cmax (the maximum observed concentration) for JTX-8064 when administered as monotherapy or in combination with a PD-1i [ Time Frame: Cycle 1 through 12 (each cycle is 21 days) ]
  • Tmax (time of maximum observed concentration) for JTX-8064 when administered as monotherapy or in combination with a PD-1i [ Time Frame: Cycle 1 through 12 (each cycle is 21 days) ]
  • Cmin for JTX-8064 when administered as monotherapy or in combination with a PD-1i [ Time Frame: Cycle 1 through 12 (each cycle is 21 days) ]
  • 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 [ Time Frame: Cycle 1 and 3 (each cycle is 21 days) ]
  • Cmax for PD-1i in combination with JTX-8064 [ Time Frame: Cycles 1 through 12 (each cycle is 21 days) ]
  • Tmax for PD-1i in combination with JTX-8064 [ Time Frame: Cycles 1 through 12 (each cycle is 21 days) ]
  • Cmin for PD-1i in combination with JTX-8064 [ Time Frame: Cycles 1 through 12 (each cycle is 21 days) ]
  • Incidence of ADAs to JTX-8064 and, as appropriate, to PD-1i [ Time Frame: Baseline through Cycle 12 (each cycle is 21 days)] ]
  • Incidence of neutralizing antibodies (Nabs) to JTX-8064 and, as appropriate, to PD-1i [ Time Frame: Baseline through Cycle 12 (each cycle is 21 days)] ]
  • For Stages 1 and 2: Receptor occupancy for LILRB2 on monocytes in whole blood [ Time Frame: Baseline through Cycle 6 (each cycle is 21 days)] ]
  • 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 [ Time Frame: up to 36 months ]
  • 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 [ Time Frame: up to 36 months ]
  • 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) [ Time Frame: up to 36 months ]
  • For Stages 3 and 4: Preliminary efficacy endpoints: Percentage of subjects with tumor reduction at any time [ Time Frame: up to 36 months ]
  • 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) [ Time Frame: up to 36 months ]
  • For Stages 3 and 4: Preliminary efficacy endpoints: Overall survival (OS) (the interval from start of treatment to death of any cause) [ Time Frame: up to 36 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2020)
  • Cmax (the maximum observed concentration) for JTX-8064 when administered as monotherapy or in combination with JTX-4014 or pembrolizumab, [ Time Frame: Cycle 1 and 3, pre-dose through 508 hours post-dose; Cycle 2 and 3 to 12, pre-dose and 1.5 hours post-dose (each cycle is 21 days) ]
  • Tmax (time of maximum observed concentration) for JTX-8064 when administered as monotherapy or in combination with JTX-4014 or pembrolizumab, [ Time Frame: Cycle 1 and 3, pre-dose through 508 hours post-dose; Cycle 2 and 3 to 12, pre-dose and 1.5 hours post-dose (each cycle is 21 days) ]
  • Cmin for JTX-8064 when administered as monotherapy or in combination with JTX-4014 or pembrolizumab, [ Time Frame: Cycle 1 and 3, pre-dose through 508 hours post-dose; Cycle 2 and 3 to 12, pre-dose and 1.5 hours post-dose (each cycle is 21 days) ]
  • 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 JTX-4014 or pembrolizumab, [ Time Frame: Cycle 1 and 3, pre-dose through 508 hours post-dose; Cycle 2 and 3 to 12, pre-dose and 1.5 hours post-dose (each cycle is 21 days) ]
  • AUCtau (area under the concentration-time curve over the dosing interval) for JTX-8064 when administered as monotherapy or in combination with JTX-4014 or pembrolizumab, [ Time Frame: Cycle 1 and 3, pre-dose through 508 hours post-dose; Cycle 2 and 3 to 12, pre-dose and 1.5 hours post-dose (each cycle is 21 days) ]
  • Cmax for JTX-4014 and pembrolizumab in combination with JTX-8064 [ Time Frame: Pre-and post-dose on Cycles 1 to 12 (each cycle is 21 days) ]
  • Tmax for JTX-4014 and pembrolizumab in combination with JTX-8064 [ Time Frame: Pre-and post-dose on Cycles 1 to 12 (each cycle is 21 days) ]
  • Cmin for JTX-4014 and pembrolizumab in combination with JTX-8064 [ Time Frame: Pre-and post-dose on Cycles 1 to 12 (each cycle is 21 days) ]
  • Incidence of ADAs to JTX-8064 and, as appropriate, to JTX-4014 or pembrolizumab [ Time Frame: Pre-dose on Cycles 1 to 12 (each cycle is 21 days) ]
  • Incidence of neutralizing antibodies (Nabs) to JTX-8064 and, as appropriate, to JTX-4014 or pembrolizumab [ Time Frame: Pre-dose on Cycles 1 to 12, (each cycle is 21 days) ]
  • Receptor occupancy for LILRB2 on monocytes and neutrophils in whole blood [ Time Frame: For Stage 1, Cycles 1 and 3, pre-dose through 508 hours post-dose and Cycle 2, pre-dose and 1.5hr post-dose; For Stage 2, Cycles 1 to 3, pre-dose and 1.5 hours post-dose (each cycle is 21 days) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of JTX 8064, as Monotherapy and in Combination With a PD-1 Inhibitor, in Adult Subjects With Advanced Refractory Solid Tumors
Official Title  ICMJE Phase 1 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
Brief Summary JTX-8064-101 is a Phase 1, 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).
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, 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
    Intervention: Drug: JTX-8064
  • 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
    Interventions:
    • Drug: JTX-8064
    • Drug: pimivalimab
  • 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
    Intervention: Drug: JTX-8064
  • 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)1-experienced clear cell renal cell carcinoma (ccRCC)
    Interventions:
    • Drug: JTX-8064
    • Drug: pimivalimab
  • 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)1-experienced triple negative breast cancer (TNBC)
    Interventions:
    • Drug: JTX-8064
    • Drug: pimivalimab
  • Experimental: Stage 4, Expansion: JTX-8064 in combination with pimivalimab (HNSCC)
    Experimental: Expansion, Stage 4: 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)
    Interventions:
    • Drug: JTX-8064
    • Drug: pimivalimab
  • Experimental: Stage 4, Expansion: JTX-8064 in combination with pimivalimab (Ovarian)
    TX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-naïve, platinum resistant ovarian cancer
    Interventions:
    • Drug: JTX-8064
    • Drug: pimivalimab
  • 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)
    Interventions:
    • Drug: JTX-8064
    • Drug: pimivalimab
  • 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)
    Interventions:
    • Drug: JTX-8064
    • Drug: pimivalimab
  • 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)
    Interventions:
    • Drug: JTX-8064
    • Drug: pimivalimab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 19, 2021)
281
Original Estimated Enrollment  ICMJE
 (submitted: December 9, 2020)
40
Estimated Study Completion Date  ICMJE January 2024
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  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.

    1. 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
    2. Stage 3: This stage may enroll subjects with the following cancers:

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

    3. 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
  3. Measurable disease, according to the RECIST version 1.1, that has objectively progressed since (or on) previous treatment as assessed by the Investigator;
  4. ≥ 18 years of age;
  5. Eastern Cooperative Oncology Group performance status 0 or 1;
  6. Predicted life expectancy of ≥ 3 months;
  7. Have specified laboratory values (obtained ≤ 28 days prior to first dose) in accordance with the study protocol;
  8. 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
  9. 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:

    1. Immunotherapy or biologic therapy < 28 days prior to planned C1D1 or 5 half-lives, whichever is shorter
    2. Chemotherapy < 21 days prior to planned C1D1, or < 42 days for mitomycin or nitrosoureas or 5 half-lives, whichever is shorter
    3. Targeted small molecule therapy < 14 days or 5 half-lives, whichever is shorter, prior to planned C1D1
    4. 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
  4. 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);
  5. 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
  6. Live vaccines ≤ 30 days of C1D1
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nancy Mota (857) 259-3840 nmota@jouncetx.com
Contact: Sasha Stann (857)999-2977 sstann@jouncetx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04669899
Other Study ID Numbers  ICMJE JTX-8064-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jounce Therapeutics, Inc.
Study Sponsor  ICMJE Jounce Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Adam Y-Beltrán, M.D Jounce Therapeutics, Inc.
PRS Account Jounce Therapeutics, Inc.
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP