Clinical Trials /

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

NCT02904226

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: JTX-2011-101
  • NCT ID: NCT02904226

Conditions

  • Cancer

Interventions

DrugSynonymsArms
JTX-2011ICOS agonist monoclonal antibodyPart A (JTX-2011)
NivolumabOpdivoPart B (JTX-2011 + nivolumab)
IpilimumabYervoyPart E (JTX-2011 + ipilimumab)
PembrolizumabKeytrudaPart G (JTX-2011 + pembrolizumab)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Part A (JTX-2011)ExperimentalPhase 1 dose escalation and expansion of JTX-2011 by intravenous (IV) infusion
  • JTX-2011
Part B (JTX-2011 + nivolumab)ExperimentalPhase 1 dose escalation and expansion of JTX-2011 by IV infusion in combination with nivolumab by IV infusion
  • JTX-2011
  • Nivolumab
Part C (JTX-2011)ExperimentalPhase 2 expansion of JTX-2011 by IV infusion
  • JTX-2011
Part D (JTX-2011 + nivolumab)ExperimentalPhase 2 expansion of JTX-2011 by IV infusion in combination with nivolumab by IV infusion
  • JTX-2011
  • Nivolumab
Part E (JTX-2011 + ipilimumab)ExperimentalPhase 1 dose escalation of JTX-2011 by IV infusion in combination with ipilimumab by IV infusion
  • JTX-2011
  • Ipilimumab
Part F (JTX-2011 + ipilimumab)ExperimentalPhase 2 expansion of JTX-2011 by IV infusion in combination with ipilimumab by IV infusion
  • JTX-2011
  • Ipilimumab
Part G (JTX-2011 + pembrolizumab)ExperimentalPhase 1 dose escalation of JTX-2011 by IV infusion in combination with pembrolizumab by IV infusion
  • JTX-2011
  • Pembrolizumab
Part H (JTX-2011 + pembrolizumab)ExperimentalPhase 2 expansion of JTX-2011 by IV infusion in combination with pembrolizumab by IV infusion
  • JTX-2011
  • Pembrolizumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:% subjects with adverse events (AEs)
Time Frame:26 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Maximum measured concentration in serum (Cmax)
Time Frame:26 months
Safety Issue:
Description:
Measure:Minimum measured concentration in serum (Cmin)
Time Frame:26 months
Safety Issue:
Description:
Measure:Time from dosing to maximum measured concentration (tmax)
Time Frame:26 months
Safety Issue:
Description:
Measure:Area under the serum concentration-time curve (AUC)
Time Frame:26 months
Safety Issue:
Description:
Measure:Terminal half-life (t1/2)
Time Frame:26 months
Safety Issue:
Description:
Measure:Mean residence time (MRT)
Time Frame:26 months
Safety Issue:
Description:
Measure:Total clearance of the analyte in serum (CL)
Time Frame:26 months
Safety Issue:
Description:
Measure:Apparent volume of distribution during specific time points
Time Frame:26 months
Safety Issue:
Description:
Measure:% target engagement
Time Frame:26 months
Safety Issue:
Description:
Measure:Area under the effect-time curve (AUEC) of the pharmacodynamics marker in serum
Time Frame:26 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jounce Therapeutics, Inc.

Trial 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

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