A phase I/Ib, open-label, multi-center, study of DKY709 as a single agent and in combination with PDR001 in patients with advanced solid tumors

This is a phase I/Ib, open label study. The escalation portion will characterize the safety
and tolerability of DKY709 and DKY709 in combination with PDR001 in subjects with NSCLC or
melanoma who have received prior anti-PD-1/PD-L1 therapy, or subjects with NPC. After the
determination of the MTD/RD for a particular treatment arm, dose expansion will further
assess safety, tolerability, PK/PD, and anti-tumor activity of each regimen at the MTD/RD.

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study.

2. Patients must be ≥18 years of age at the time of informed consent form (ICF)
signature.

3. Patients with advanced/metastatic cancer who have progressed despite having received
standard therapy in the metastatic setting or are intolerant to standard therapy, and
for whom no effective standard therapy is available

4. In expansion: patient with measurable disease as determined by RECIST version 1.1,

5. Dose escalation, patients must fit into one of the following groups:

- NSCLC, previously treated with an anti-PD-1/PD-L1 therapy

- Cutaneous Melanoma, previously treated with an anti-PD-1/PD-L1 therapy

- NPC

Dose expansion part, patients must fit into one of the following groups:

- NSCLC with historic documentation of PD-L1 ≥ 1%. Patients must have progressive
disease after having experienced at least 4 months of investigator-assessed
disease stability or response on prior anti-PD-L1-containing therapy

- Cutaneous Melanoma, previously treated with anit-PD-1/PD-L1 therapy. Patients
should have documented progression following anti-PD-1/PD-L1 therapy.

- NPC, naive to anti-PD-1/PD-L1 therapy

- mssCRC, naive to anti-PD-1/PD-L1 therapy

- TNBC, naive to anti-PD-1/PD-L1 therapy

6. ECOG Performance Status ≤ 1

7. Patients must have a site of disease amenable to core needle biopsy, and be a
candidate for tumor biopsy according to the treating institution's guidelines.
Patients must be willing to undergo a new tumor biopsy at baseline, and during therapy
on the study. Exceptions may be considered after documented discussion with Novartis.

Exclusion Criteria:

1. Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases
that require local CNS-directed therapy (such as radiotherapy or surgery), or
increasing doses of corticosteroids within 2 weeks prior to study entry. Patients with
treated brain metastases should be neurologically stable for at least 4 weeks prior to
study entry and off steroids for at least 2 weeks before administration of any study
treatment.

2. History of severe hypersensitivity reactions to any ingredient of study drug(s) or
other mAbs and/or their excipients.

3. Patient with out of range laboratory values defined as:

- Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 40
mL/min

- Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are
excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN

- Alanine aminotransferase (ALT) > 3 x ULN, except for patients that have tumor
involvement of the liver, who are excluded if ALT > 5 x ULN

- Aspartate aminotransferase (AST) > 3 x ULN, except for patients that have tumor
involvement of the liver, who are excluded if AST > 5 x ULN

- Absolute neutrophil count (ANC) < 1.0 x 109/L

- Platelet count < 75 x 109/L (growth factor or transfusion support may not be used
to meet entry criterion)

- Hemoglobin (Hgb) < 8 g/dL (growth factor or transfusion support may not be used
to meet entry criterion)

- Magnesium, calcium or phosphate abnormality CTCAE > grade 1

- Potassium abnormality CTCAE ≥ grade 1; supplementation to meet eligibility
criteria is acceptable

4. Clinically significant cardiac disease or impaired cardiac function, including any of
the following:

- Clinically significant and/or uncontrolled heart disease such as congestive heart
failure requiring treatment (NYHA grade ≥ 2), uncontrolled hypertension or
clinically significant arrhythmia

- On screening: QTcF > 450 msec (male), or > 460 msec (female)

- QTc not assessable

- Congenital long QT syndrome

- History of familial long QT syndrome or known family history of as Torsades de
Pointes

- Acute myocardial infarction or unstable angina pectoris < 3 months prior to study
entry