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

Solid Tumors Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03301896
• Other study ID #: CLHC165X2101
• Status: Terminated
• Phase: Phase 1
• Start date: January 31, 2018
• Est. completion date: June 30, 2022

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 45
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• LHC165
LHC165 intratumoral injection

Biological:
• PDR001
PDR001 infusion

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Wilrijk
Germany	Novartis Investigative Site	Ulm
Italy	Novartis Investigative Site	Milano	MI
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Korea, Republic of	Novartis Investigative Site	Seoul
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
United States	MD Anderson Cancer Center	Houston	Texas
United States	UCLA	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Italy,  Japan,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1	Dose Limiting Toxicity Evaluation Period	day 28
Primary	Escalation and Expansion: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), including changes in laboratory parameters, vital signs, electrocardiograms (ECGs)		24 months
Secondary	Objective Response Rate (ORR) per RECIST 1.1 and iRECIST		24 months
Secondary	Best Overall Response (BOR) per RECIST 1.1 and iRECIST		24 months
Secondary	Progression-Free Survival (PFS) per RECIST 1.1 and iRECIST		24 months
Secondary	Duration of Response (DOR) per RECIST 1.1 and iRECIST		24 months
Secondary	Disease Control Rate (DCR) per RECIST 1.1 and iRECIST		24 months
Secondary	Serum concentration profiles of LHC165 as a single agent: Cmax		24 months
Secondary	Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Cmax		24 months
Secondary	Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Cmax		24 months
Secondary	Serum concentration profiles of LHC165 as a single agent: AUC		24 months
Secondary	Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: AUC		24 months
Secondary	Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: AUC		24 months
Secondary	Serum concentration profiles of LHC165 as a single agent: Tmax		24 months
Secondary	Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: Tmax		24 months
Secondary	Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Tmax		24 months
Secondary	Presence and titer of anti-PDR001 antibodies		24 months
Secondary	Change from baseline in tumor infiltrating lymphocytes in injected and distal tumor specimens		24 months

External Links

•   Plain Language Trial Summary
•   Study Results