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

NCT03301896 | Terminated Phase 1 FDA Drug

• 1 other identifier: CLHC165X2101
• Study Type: interventional
• Target: 45
• Locations: 7 countries
• Sites: 9

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

Conditions

Solid Tumors

Keywords

Phase I; LHC165; PDR001; intratumoral injection; abscopal; checkpoint inhibitor; programmed cell death; PD-1; TLR-7; toll-like receptor; melanoma; head and neck

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (16)

• 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

Study Arms (2)

LHC165 single agent

EXPERIMENTAL

LHC165 intratumoral injection given alone

Drug: LHC165

LHC165 in combination with PDR001

EXPERIMENTAL

LHC165 intratumoral injection given with PDR001 infusion

Drug: LHC165; Biological: PDR001

Interventions

LHC165 DRUG

LHC165 intratumoral injection

LHC165 in combination with PDR001; LHC165 single agent

PDR001 BIOLOGICAL

PDR001 infusion

LHC165 in combination with PDR001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

UCLA

Los Angeles, California, 90095, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Wilrijk, 2610, Belgium

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104 0045, Japan

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Related Links

• Study Results
• Plain Language Trial Summary

MeSH Terms

Conditions

Melanoma

Interventions

spartalizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Nehal Parikh, MD

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 4, 2017
• Study Start: January 31, 2018
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: June 20, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1); DE (1); US (2); IT (1); ES (2); BE (1); KR (1)