Clinical Trials /

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

NCT04669899

Description:

JTX-8064-101 is a Phase 1, open label, dose escalation clinical study to determine the safety, tolerability, and recommended Phase 2 dose of JTX-8064 alone and in combination with either JTX-4014 or pembrolizumab.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: JTX-8064-101
  • NCT ID: NCT04669899

Conditions

  • Cancer

Interventions

DrugSynonymsArms
JTX-8064Stage 1, Dose Escalation: JTX-8064 monotherapy dose escalation
JTX-4014Stage 2, Dose Escalation: JTX-8064 in combination with JTX-4014 or pembrolizumab
PembrolizumabStage 2, Dose Escalation: JTX-8064 in combination with JTX-4014 or pembrolizumab

Purpose

JTX-8064-101 is a Phase 1, open label, dose escalation clinical study to determine the safety, tolerability, and recommended Phase 2 dose of JTX-8064 alone and in combination with either JTX-4014 or pembrolizumab.

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 clinical trial to determine
      the safety, tolerability, MTD and RP2D of JTX-8064 when administered as a single agent and in
      combination with JTX-4014 or pembrolizumab to adult subjects with advanced refractory solid
      tumor malignancies. Additionally, the study will seek to evaluate the pharmacokinetics and
      immunogenicity of JTX-8064.
    

Trial Arms

NameTypeDescriptionInterventions
Stage 1, Dose Escalation: JTX-8064 monotherapy dose escalationExperimentalStage 1 will evaluate JTX-8064 monotherapy dose escalation by intravenous infusion
  • JTX-8064
Stage 2, Dose Escalation: JTX-8064 in combination with JTX-4014 or pembrolizumabExperimentalStage 2 will evaluate JTX-8064 dose escalation in combination with JTX-4014 or pembrolizumab by intravenous infusion
  • JTX-8064
  • JTX-4014
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          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. Subject must have received, have been intolerant to, have been ineligible
             for, or have declined all treatment known to confer clinical benefit;

          3. Able/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 laboratory values (obtained ≤ 28 days prior to first infusion day) in accordance
             with the study protocol;

          8. For women of childbearing potential (WOCBP): negative serum pregnancy test within 72
             hours prior to planned Cycle 1 Day 1 (C1D1) and a negative urine pregnancy test on
             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 Food and Drug Administration (FDA)-approved or
             investigational, for the cancer being evaluated in this study or for prior
             malignancies. Concurrent malignancies that do not require treatment and are clinically
             stable are allowed;

          2. Prior infusion of JTX-8064, LILRB2, or Immunoglobulin-like Transcript 4
             (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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Evaluated using National Cancer Institute (NCI) Common Technology Criteria for Adverse Events (CTCAE) version 5.0

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jounce Therapeutics, Inc.

Trial Keywords

  • JTX-8064
  • LILRB2
  • ILT-4
  • PD-1
  • JTX-4014
  • Immunotherapy
  • Immuno-oncology
  • Solid tumor Malignancies
  • Dose escalation
  • INNATE
  • Monotherapy
  • Combination Therapy

Last Updated

December 17, 2020