TerminatedNCT03301896Updated Jun 20, 2024

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

A Phase 1 interventional study of LHC165 and PDR001 in Solid Tumors, sponsored by Novartis Pharmaceuticals. Terminated at 9 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-20.

Sponsored by Novartis Pharmaceuticals · Phase 1, Interventional, and Treatment

Why this study was terminated

Business reasons

Phase: Phase 1
Study type: Interventional
Enrollment: 45
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

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

Read the 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.

Conditions studied

Solid Tumors

Browse trials for

Neoplasms 9,328

Keywords

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

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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 design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 45 participants (actual)

Study arms

Experimental
LHC165 single agent
LHC165 intratumoral injection given alone
Drug: LHC165
Experimental
LHC165 in combination with PDR001
LHC165 intratumoral injection given with PDR001 infusion
Drug: LHC165 · Biological: PDR001

Interventions

DrugLHC165
LHC165 intratumoral injection
BiologicalPDR001
PDR001 infusion

What researchers measure

Primary outcomes

Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1
Dose Limiting Toxicity Evaluation Period
Time frame: 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

Secondary outcomes

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

Study locations

9 sites

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

References and documents

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT03301896
Lead sponsor: Novartis Pharmaceuticals
Responsible party: Sponsor
First posted: Oct 4, 2017
Start date: Jan 31, 2018
Primary completion: Jun 30, 2022
Completion: Jun 30, 2022
Last update: Jun 20, 2024

Study contacts

Nehal Parikh, MD

study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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