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
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
UCLA
Los Angeles, California, United States
MD Anderson Cancer Center
Houston, Texas, United States
Novartis Investigative Site
Wilrijk, Belgium
Novartis Investigative Site
Ulm, Germany
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
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
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Novartis Investigative Site
Milan, MI, Italy
Novartis Investigative Site
Chuo Ku, Tokyo, Japan
Novartis Investigative Site
Seoul, South Korea
Novartis Investigative Site
Barcelona, Catalonia, Spain
Novartis Investigative Site
Madrid, Spain
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