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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 April 2023
• Main ID: NCT03301896
• Date of registration: 29/09/2017
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Study of the Safety and Efficacy of LHC165 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies
• Scientific 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
• Date of first enrolment: January 31, 2018
• Target sample size: 45
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03301896
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

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

Contacts

• Name: Nehal Parikh, MD
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Solid Tumors

Intervention(s)

Drug: LHC165

Biological: PDR001

Primary Outcome(s)

Escalation: Incidence of Dose-limiting Toxicities (DLTs) in Cycle 1 [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]

Secondary Outcome(s)

Duration of Response (DOR) per RECIST 1.1 and iRECIST [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 in combination with PDR001 and derived PK parameters: Cmax [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]

Progression-Free Survival (PFS) per RECIST 1.1 and iRECIST [Time Frame: 24 months]

Serum concentration profiles of LHC165 in combination with PDR001 and derived PK parameters: AUC [Time Frame: 24 months]

Presence and titer of anti-PDR001 antibodies [Time Frame: 24 months]

Serum concentration profiles of LHC165 as a single agent: Tmax [Time Frame: 24 months]

Change from baseline in tumor infiltrating lymphocytes in injected and distal tumor specimens [Time Frame: 24 months]

Serum concentration profiles of PDR001 in combination with LHC165 and derived PK parameters: Cmax [Time Frame: 24 months]

Best Overall Response (BOR) 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: AUC [Time Frame: 24 months]

Serum concentration profiles of LHC165 as a single agent: Cmax [Time Frame: 24 months]

Objective Response Rate (ORR) per RECIST 1.1 and iRECIST [Time Frame: 24 months]

Secondary ID(s)

CLHC165X2101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors