Clinical trial NCT03301896: Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Phase I
LHC165
PDR001
intratumoral injection
abscopal
checkpoint inhibitor
programmed cell death
PD-1
TLR-7
toll-like receptor
melanoma
head and neck
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-10-04
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

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.

Eligibility 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

Primary outcomes:
measure: Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1
timeFrame: day 28
measure: Escalation and Expansion: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), including changes in laboratory parameters, vital signs, electrocardiograms (ECGs)
timeFrame: 24 months
Secondary outcomes:
measure: Objective Response Rate (ORR) per RECIST 1.1 and iRECIST
timeFrame: 24 months
measure: Best Overall Response (BOR) per RECIST 1.1 and iRECIST
timeFrame: 24 months
measure: Progression-Free Survival (PFS) per RECIST 1.1 and iRECIST
timeFrame: 24 months
measure: Duration of Response (DOR) per RECIST 1.1 and iRECIST
timeFrame: 24 months
measure: Disease Control Rate (DCR) per RECIST 1.1 and iRECIST
timeFrame: 24 months
measure: Serum concentration profiles of LHC165 as a single agent: Cmax
timeFrame: 24 months
measure: Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Cmax
timeFrame: 24 months
measure: Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Cmax
timeFrame: 24 months
measure: Serum concentration profiles of LHC165 as a single agent: AUC
timeFrame: 24 months
measure: Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: AUC
timeFrame: 24 months
measure: Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: AUC
timeFrame: 24 months
measure: Serum concentration profiles of LHC165 as a single agent: Tmax
timeFrame: 24 months
measure: Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Tmax
timeFrame: 24 months
measure: Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Tmax
timeFrame: 24 months
measure: Presence and titer of anti-PDR001 antibodies
timeFrame: 24 months
measure: Change from baseline in tumor infiltrating lymphocytes in injected and distal tumor specimens
timeFrame: 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Wilrijk
country: Belgium
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Nehal Parikh, MD
role: STUDY_DIRECTOR
References: