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Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies

NCT03301896

Description:

The purpose of this trial is to explore the clinical utility of two investigational agents in patients with advanced cancer. This is a multi-center, open-label Phase I/Ib study. The study consists of four dose escalation parts and two dose expansion parts testing LHC165 as a single agent or LHC165 in combination with PDR001. The dose escalation parts will estimate the Maximum Tolerated Dose (MTD) and/or Recommended Dose for Expansion (RDE) and test two different dosing schedules for LHC165. The dose expansion parts of the study will use the MTD/RDE for each the LHC165 single agent and in combination with PDR001, determined in the respective dose escalation parts to assess the activity, safety and tolerability of LHC165 as a single agent or LHC165 in combination with PDR001 in patients with specific types of solid tumors. Approximately 206 adult patients with advanced solid tumors will be enrolled.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies
  • Official Title: A Phase I/Ib, Open-label, Multi-center Dose-escalation and Dose-expansion Study of the Safety and Tolerability of Intra-tumorally Administered LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: CLHC165X2101
  • NCT ID: NCT03301896

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
LHC165LHC165 single agent
PDR001LHC165 in combination with PDR001

Purpose

The purpose of this trial is to explore the clinical utility of two investigational agents in patients with advanced cancer. This is a multi-center, open-label Phase I/Ib study. The study consists of four dose escalation parts and two dose expansion parts testing LHC165 as a single agent or LHC165 in combination with PDR001. The dose escalation parts will estimate the Maximum Tolerated Dose (MTD) and/or Recommended Dose for Expansion (RDE) and test two different dosing schedules for LHC165. The dose expansion parts of the study will use the MTD/RDE for each the LHC165 single agent and in combination with PDR001, determined in the respective dose escalation parts to assess the activity, safety and tolerability of LHC165 as a single agent or LHC165 in combination with PDR001 in patients with specific types of solid tumors. Approximately 206 adult patients with advanced solid tumors will be enrolled.

Detailed Description

      This is a Phase I/Ib, multi-center, open-label study to characterize the safety,
      tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor
      activity of LHC165 single agent and in combination with the Programmed Cell Death Protein-1
      (PD-1) checkpoint inhibitor PDR001. Two different dosing schedules will be explored for
      LHC165 single agent and in combination with PDR001 resulting in four dose escalation groups
      in accessible tumors. The first dose escalation group will receive LHC165 via intratumoral
      injection on Days 1 and 15 of Cycles 1, 2, 5, and 6. If biological activity is seen in the
      LHC165 single agent group on the biweekly dosing schedule, another dose escalation group
      using a monthly dosing schedule will be opened where patients will receive LHC165 via
      intratumoral injection on Day 1 of Cycles 1, 2, 5, and 6. In addition, once two safe doses
      are observed in the LHC165 single agent group on the biweekly dosing schedule, an LHC165
      combination with PDR001 dose escalation group will be opened using the biweekly dosing
      schedule. If biological activity is seen in the LHC165 combination with PDR001 group on the
      biweekly dosing schedule, another dose escalation group for the combination using a monthly
      dosing schedule will be opened.

      Once the recommended dose for the LHC165 single agent and in combination with PDR001 is
      identified, the respective expansion parts of the study will open.
    

Trial Arms

NameTypeDescriptionInterventions
LHC165 single agentExperimentalLHC165 intratumoral injection given alone
  • LHC165
LHC165 in combination with PDR001ExperimentalLHC165 intratumoral injection given with PDR001 infusion
  • LHC165
  • PDR001

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent must be obtained prior to any procedures unless considered
             standard of care.

          -  Adult men and women (≥ 18 years of age) with histologically confirmed diagnosis of
             metastatic and/or advanced solid tumors not amenable to curative treatment by surgery.

          -  Patients must be willing and able to comply with the protocol for the duration of the
             study including undergoing treatment and scheduled visits and examinations including
             follow up.

          -  Dose escalation: Patients with accessible tumors and with measurable disease as
             determined by RECIST 1.1 and have progressed despite standard treatment or are
             intolerant of standard treatment, or for whom no standard treatment exists.

          -  Dose expansion: Patients with advanced/metastatic solid tumors: HNSCC, melanoma,
             accessible tumors and visceral tumors (LHC165 combination with PDR001 only). Patients
             must have measurable disease as determined by RECIST 1.1 and have progressed despite
             standard treatment or are intolerant to standard treatment, or for whom no standard
             treatment exists• Patients must have at least two sites of disease amenable to biopsy.

          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

        Exclusion Criteria:

          -  Presence of symptomatic or uncontrolled central nervous system (CNS) metastases
             requiring local CNS-directed treatment.

          -  Patients diagnosed with hematological malignancies.

          -  Patients with prior stem cell transplants.

          -  Patients previously treated with TLR-7/8 agonist treatment.

          -  History of primary immunodeficiency

          -  Patients who discontinued prior anti-PD-1/PD-L1 therapy due to an
             anti-PD-1/PD-L1-related toxicity.

          -  Malignant disease, other than that being treated in this study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1
Time Frame:day 28
Safety Issue:
Description:Dose Limiting Toxicity Evaluation Period

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) per RECIST 1.1 and iRECIST
Time Frame:24 months
Safety Issue:
Description:
Measure:Best Overall Response (BOR) per RECIST 1.1 and iRECIST
Time Frame:24 months
Safety Issue:
Description:
Measure:Progression-Free Survival (PFS) per RECIST 1.1 and iRECIST
Time Frame:24 months
Safety Issue:
Description:
Measure:Duration of Response (DOR) per RECIST 1.1 and iRECIST
Time Frame:24 months
Safety Issue:
Description:
Measure:Disease Control Rate (DCR) per RECIST 1.1 and iRECIST
Time Frame:24 months
Safety Issue:
Description:
Measure:Serum concentration profiles of LHC165 as a single agent: Cmax
Time Frame:24 months
Safety Issue:
Description:
Measure:Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Cmax
Time Frame:24 months
Safety Issue:
Description:
Measure:Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Cmax
Time Frame:24 months
Safety Issue:
Description:
Measure:Serum concentration profiles of LHC165 as a single agent: AUC
Time Frame:24 months
Safety Issue:
Description:
Measure:Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: AUC
Time Frame:24 months
Safety Issue:
Description:
Measure:Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: AUC
Time Frame:24 months
Safety Issue:
Description:
Measure:Serum concentration profiles of LHC165 as a single agent: Tmax
Time Frame:24 months
Safety Issue:
Description:
Measure:Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Tmax
Time Frame:24 months
Safety Issue:
Description:
Measure:Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Tmax
Time Frame:24 months
Safety Issue:
Description:
Measure:Presence and titer of anti-PDR001 antibodies
Time Frame:24 months
Safety Issue:
Description:
Measure:Change from baseline in tumor infiltrating lymphocytes in injected and distal tumor specimens
Time Frame:24 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Phase I
  • LHC165
  • PDR001
  • intratumoral injection
  • abscopal
  • checkpoint inhibitor
  • programmed cell death
  • PD-1
  • TLR-7
  • toll-like receptor
  • melanoma
  • head and neck

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