Summary

for people ages 18 years and up (full criteria)
at UCLA
study started
estimated completion

Description

Summary

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.

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

Details

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.

Keywords

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

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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.

You CAN'T join if...

  • 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

Locations

  • Novartis Investigative Site accepting new patients
    Los Angeles California 90095 United States
  • Novartis Investigative Site accepting new patients
    Houston Texas 77030 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
ID
NCT03301896
Phase
Phase 1
Study Type
Interventional
Last Updated