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

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

The purpose of this trial was to explore the clinical utility of two investigational agents in patients with advanced cancer.

This was a multi-center, open-label Phase I/Ib study. The primary objectives of the trial were:

• To characterize the safety and tolerability of intratumoral LHC165 in patients with solid tumors as a single agent and in combination with PDR001
• To determine and evaluate the maximum tolerated dose (MTD)/recommended dose (RD) for LHC165 as a single agent and in combination with PDR001

Study Overview

• Status: Terminated
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: LHC165; Biological: PDR001

Detailed Description

This was a multi-center, open-label Phase I/Ib study. The study consisted 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 estimated the Maximum Tolerated Dose (MTD) and/or Recommended Dose for Expansion (RDE) and were planned to test two different dosing schedules for LHC165 single agent (Group A and B) and LHC165 in combination with PDR001 (Group C and D).

The dose expansion parts of the study were planned to use the MTD/RDE for each the LHC165 single agent (Group E) and LHC165 in combination with PDR001 (Group F), 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.

The study was terminated due to business reasons. Groups B, D and E were not opened for enrollment.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Wilrijk, Belgium, 2610
    • Novartis Investigative Site
• Germany
  • Ulm, Germany, 89081
    • Novartis Investigative Site
• Italy
  • MI
    • Milano, MI, Italy, 20141
      • Novartis Investigative Site
• Japan
  • Tokyo
    • Chuo ku, Tokyo, Japan, 104 0045
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1	Dose Limiting Toxicity Evaluation Period	day 28
Escalation and Expansion: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), including changes in laboratory parameters, vital signs, electrocardiograms (ECGs)		24 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Nehal Parikh, MD, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Study Results

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2018
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: September 29, 2017
• First Submitted That Met QC Criteria: September 29, 2017
• First Posted (Actual): October 4, 2017

Study Record Updates

• Last Update Posted (Actual): April 7, 2023
• Last Update Submitted That Met QC Criteria: April 5, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Phase I; PD-1; melanoma; PDR001; checkpoint inhibitor; head and neck; intratumoral injection; LHC165; abscopal; programmed cell death; TLR-7; toll-like receptor
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immune Checkpoint Inhibitors; Spartalizumab
• Other Study ID Numbers: CLHC165X2101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No