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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: LHC165
* Biological: PDR001


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LHC165 single agent<br>LHC165 intratumoral injection given alone | Drug: LHC165<br>* LHC165 intratumoral injection<br>|
| Experimental: LHC165 in combination with PDR001<br>LHC165 intratumoral injection given with PDR001 infusion | Drug: LHC165<br>* LHC165 intratumoral injection<br>Biological: PDR001<br>* PDR001 infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1 | Dose Limiting Toxicity Evaluation Period | 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) |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, LHC165, PDR001, intratumoral injection, abscopal, checkpoint inhibitor, programmed cell death, PD-1, TLR-7, toll-like receptor, melanoma, head and neck