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

This is a Phase I/Ib, multi-center, open-label study to characterize the safety,
tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor
activity of LHC165 single agent and in combination with the Programmed Cell Death Protein-1
(PD-1) checkpoint inhibitor PDR001. Two different dosing schedules will be explored for
LHC165 single agent and in combination with PDR001 resulting in four dose escalation groups
in accessible tumors. The first dose escalation group will receive LHC165 via intratumoral
injection on Days 1 and 15 of Cycles 1, 2, 5, and 6. If biological activity is seen in the
LHC165 single agent group on the biweekly dosing schedule, another dose escalation group
using a monthly dosing schedule will be opened where patients will receive LHC165 via
intratumoral injection on Day 1 of Cycles 1, 2, 5, and 6. In addition, once two safe doses
are observed in the LHC165 single agent group on the biweekly dosing schedule, an LHC165
combination with PDR001 dose escalation group will be opened using the biweekly dosing
schedule. If biological activity is seen in the LHC165 combination with PDR001 group on the
biweekly dosing schedule, another dose escalation group for the combination using a monthly
dosing schedule will be opened.

Once the recommended dose for the LHC165 single agent and in combination with PDR001 is
identified, the respective expansion parts of the study will open.

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