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

June 17, 2024 updated by: Novartis Pharmaceuticals

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
45

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1
Time Frame: day 28
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)
Time Frame: 24 months
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Objective Response Rate (ORR) per RECIST 1.1 and iRECIST
Time Frame: 24 months
24 months
Best Overall Response (BOR) per RECIST 1.1 and iRECIST
Time Frame: 24 months
24 months
Progression-Free Survival (PFS) per RECIST 1.1 and iRECIST
Time Frame: 24 months
24 months
Duration of Response (DOR) per RECIST 1.1 and iRECIST
Time Frame: 24 months
24 months
Disease Control Rate (DCR) per RECIST 1.1 and iRECIST
Time Frame: 24 months
24 months
Serum concentration profiles of LHC165 as a single agent: Cmax
Time Frame: 24 months
24 months
Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Cmax
Time Frame: 24 months
24 months
Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Cmax
Time Frame: 24 months
24 months
Serum concentration profiles of LHC165 as a single agent: AUC
Time Frame: 24 months
24 months
Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: AUC
Time Frame: 24 months
24 months
Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: AUC
Time Frame: 24 months
24 months
Serum concentration profiles of LHC165 as a single agent: Tmax
Time Frame: 24 months
24 months
Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Tmax
Time Frame: 24 months
24 months
Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Tmax
Time Frame: 24 months
24 months
Presence and titer of anti-PDR001 antibodies
Time Frame: 24 months
24 months
Change from baseline in tumor infiltrating lymphocytes in injected and distal tumor specimens
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Nehal Parikh, MD, Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 31, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 29, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 29, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 4, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 20, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 17, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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