Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
CLHC165X2101
- NCT ID:
NCT03301896
Conditions
Interventions
Drug | Synonyms | Arms |
---|
LHC165 | | LHC165 in combination with PDR001 |
PDR001 | | LHC165 in combination with PDR001 |
Purpose
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.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
LHC165 single agent | Experimental | LHC165 intratumoral injection given alone | |
LHC165 in combination with PDR001 | Experimental | LHC165 intratumoral injection given with PDR001 infusion | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1 |
Time Frame: | day 28 |
Safety Issue: | |
Description: | Dose Limiting Toxicity Evaluation Period |
Secondary Outcome Measures
Measure: | Objective Response Rate (ORR) per RECIST 1.1 and iRECIST |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Best Overall Response (BOR) per RECIST 1.1 and iRECIST |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Progression-Free Survival (PFS) per RECIST 1.1 and iRECIST |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Duration of Response (DOR) per RECIST 1.1 and iRECIST |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Disease Control Rate (DCR) per RECIST 1.1 and iRECIST |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Serum concentration profiles of LHC165 as a single agent: Cmax |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Cmax |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Cmax |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Serum concentration profiles of LHC165 as a single agent: AUC |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: AUC |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: AUC |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Serum concentration profiles of LHC165 as a single agent: Tmax |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Tmax |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Tmax |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Presence and titer of anti-PDR001 antibodies |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Measure: | Change from baseline in tumor infiltrating lymphocytes in injected and distal tumor specimens |
Time Frame: | 24 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- Phase I
- LHC165
- PDR001
- intratumoral injection
- abscopal
- checkpoint inhibitor
- programmed cell death
- PD-1
- TLR-7
- toll-like receptor
- melanoma
- head and neck
Last Updated
May 14, 2021