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

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ClinicalTrials.gov Identifier: NCT03301896
Recruitment Status : Recruiting
First Posted : October 4, 2017
Last Update Posted : December 12, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief 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.


Condition or disease Intervention/treatment Phase
Solid Tumors Drug: LHC165 Biological: PDR001 Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 31, 2018
Estimated Primary Completion Date : April 16, 2021
Estimated Study Completion Date : December 20, 2021

Arm Intervention/treatment
Experimental: LHC165 single agent
LHC165 intratumoral injection given alone
Drug: LHC165
LHC165 intratumoral injection

Experimental: LHC165 in combination with PDR001
LHC165 intratumoral injection given with PDR001 infusion
Drug: LHC165
LHC165 intratumoral injection

Biological: PDR001
PDR001 infusion




Primary Outcome Measures :
  1. Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1 [ Time Frame: day 28 ]
    Dose Limiting Toxicity Evaluation Period

  2. Escalation and Expansion: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), including changes in laboratory parameters, vital signs, electrocardiograms (ECGs) [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Objective Response Rate (ORR) per RECIST 1.1 and iRECIST [ Time Frame: 24 months ]
  2. Best Overall Response (BOR) per RECIST 1.1 and iRECIST [ Time Frame: 24 months ]
  3. Progression-Free Survival (PFS) per RECIST 1.1 and iRECIST [ Time Frame: 24 months ]
  4. Duration of Response (DOR) per RECIST 1.1 and iRECIST [ Time Frame: 24 months ]
  5. Disease Control Rate (DCR) per RECIST 1.1 and iRECIST [ Time Frame: 24 months ]
  6. Serum concentration profiles of LHC165 as a single agent: Cmax [ Time Frame: 24 months ]
  7. Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Cmax [ Time Frame: 24 months ]
  8. Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Cmax [ Time Frame: 24 months ]
  9. Serum concentration profiles of LHC165 as a single agent: AUC [ Time Frame: 24 months ]
  10. Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: AUC [ Time Frame: 24 months ]
  11. Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: AUC [ Time Frame: 24 months ]
  12. Serum concentration profiles of LHC165 as a single agent: Tmax [ Time Frame: 24 months ]
  13. Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Tmax [ Time Frame: 24 months ]
  14. Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Tmax [ Time Frame: 24 months ]
  15. Presence and titer of anti-PDR001 antibodies [ Time Frame: 24 months ]
  16. Change from baseline in tumor infiltrating lymphocytes in injected and distal tumor specimens [ Time Frame: 24 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03301896


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, California
Novartis Investigative Site Recruiting
Los Angeles, California, United States, 90095
United States, Texas
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77030
Belgium
Novartis Investigative Site Recruiting
Wilrijk, Belgium, 2610
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20141
Japan
Novartis Investigative Site Recruiting
Chuo-ku, Tokyo, Japan, 104-0045
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 03080
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Madrid, Spain, 28007
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Nehal Parikh, MD Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03301896     History of Changes
Other Study ID Numbers: CLHC165X2101
First Posted: October 4, 2017    Key Record Dates
Last Update Posted: December 12, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
PDR001
Phase I
LHC165
intratumoral injection
abscopal
checkpoint inhibitor
programmed cell death
PD-1
TLR-7
toll-like receptor
melanoma
head and neck