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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT03301896

Collaborator

(none)

Enrollment

Locations

Arms

52.9

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: LHC165 Biological: PDR001	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 31, 2018

Actual Primary Completion Date :

Jun 30, 2022

Actual Study Completion Date :

Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LHC165 single agent LHC165 intratumoral injection given alone	Drug: LHC165 LHC165 intratumoral injection
Experimental: LHC165 in combination with PDR001 LHC165 intratumoral injection given with PDR001 infusion	Drug: LHC165 LHC165 intratumoral injection Biological: PDR001 PDR001 infusion

Arm

Intervention/Treatment

Experimental: LHC165 single agent

LHC165 intratumoral injection given alone

Drug: LHC165

LHC165 intratumoral injection

Experimental: LHC165 in combination with PDR001

LHC165 intratumoral injection given with PDR001 infusion

Drug: LHC165

LHC165 intratumoral injection

Biological: PDR001

PDR001 infusion

Outcome Measures

Primary Outcome Measures

Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1 [day 28]
Dose Limiting Toxicity Evaluation Period
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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA	Los Angeles	California	United States	90095
2	MD Anderson Cancer Center	Houston	Texas	United States	77030
3	Novartis Investigative Site	Wilrijk		Belgium	2610
4	Novartis Investigative Site	Ulm		Germany	89081
5	Novartis Investigative Site	Milano	MI	Italy	20141
6	Novartis Investigative Site	Chuo ku	Tokyo	Japan	104 0045
7	Novartis Investigative Site	Seoul		Korea, Republic of	03080
8	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
9	Novartis Investigative Site	Madrid		Spain	28009