A Study of DKN-01 in Combination With Paclitaxel or Pembrolizumab

Part A is a Dose-Escalation Study in Participants with Relapsed or Refractory Esophageal
Cancer or Gastro-Esophageal Junction Tumors. Parts B, C, D and E are expansion cohorts of
Patients with Relapsed or Refractory Esophageal Cancer, Gastro-Esophageal Junction Tumors and
Gastric Adenocarcinoma.

Part F is a Dose-Escalation and Expansion Cohorts with DKN-01 + Pembrolizumab in Patients
with Recurrent or Metastatic Esophageal Cancer, Gastroesophageal Junction Cancer or Gastric
Adenocarcinoma with Wnt Signaling Alterations.

Patients who are unable to receive paclitaxel or pembrolizumab for any reason will be allowed
to receive single agent DKN-01 as part of a monotherapy substudy.

Inclusion Criteria:

In advanced esophagogastric malignancies:

- Participants with histologically confirmed recurrent or metastatic esophageal or
gastro-esophageal junction squamous cell or adenocarcinoma or gastric adenocarcinoma
with Wnt Signaling Alterations

- Participants must be refractory or intolerant to at least one prior therapy(ies) for
metastatic or locally advanced disease

- If prior therapy consisted of palliative chemoradiation therapy, it will be
considered one line of therapy

- Prior treatment with paclitaxel as part of a definitive therapy regimen is
acceptable. Patients who are unable to receive paclitaxel for any reason will be
allowed to receive DKN-01 as a single agent.

- Prior treatment anti- programmed death-1 (PD-1)/ anti-PD-ligand 1 (PD-L1)
monoclonal antibody (mAb) is permitted in patients provided the patient's disease
is primary refractory, and the patient is not intolerant of pembrolizumab.
Patients who are not eligible to receive pembrolizumab will be allowed to receive
single agent DKN-01

- Tumor tissue for mandatory evaluation

- Must have one or more tumors measurable on radiographic imaging as defined by the
Response Evaluation Criteria in Solid Tumors (RECIST). Patients with evaluable but not
measurable disease per RECIST criteria may be enrolled with the approval of the
medical monitor.

- Must be ≥18 years of age

- Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale. A
performance status of 2 on the ECOG scale may be entered upon the review and approval
of the medical monitor

- Disease-free of active second/secondary or prior malignancies for equal to or over 2
years with the exception of currently treated basal cell, squamous cell carcinoma of
the skin, or carcinoma "in-situ" of the cervix or breast

- Acceptable liver, renal, hematologic and coagulation function

- For men and women of child-producing potential, the use of effective contraceptive
methods during the study and for 6 months following the last dose of study drug

Exclusion Criteria:

- New York Heart Association Class III or IV, cardiac disease, myocardial infarction
within the past 6 months, unstable arrhythmia

- Fridericia-corrected QT interval (QTcF) > 470 msec (female) or > 450 (male), or
history of congenital long QT syndrome.

- Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study
entry requiring systemic therapy

- Known to be human immunodeficiency virus (HIV) positive, have hepatitis B surface
antigen (HBSAg), or hepatitis C antibodies (HCAb) unless HCV RNA is
undetected/negative.

- Serious nonmalignant disease

- Pregnant or nursing women

- History of osteonecrosis of the hip or have evidence of structural bone abnormalities
in the proximal femur on MRI scan that are symptomatic and clinically significant.

- Systemic central nervous system (CNS) malignancy or metastasis.

- Clinically significant peripheral neuropathy at the time of study entry. Patients with
pre-existing peripheral neuropathy will be allowed to receive single agent DKN-01

- Known osteoblastic bony metastasis

- History of known or suspected autoimmune disease with the specific exceptions of
vitiligo, atopic dermatitis, or psoriasis not requiring systemic treatment.

- Clinically-significant gastrointestinal disorders, such as perforation,
gastrointestinal bleeding, or diverticulitis.

- Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (thyroxine, insulin, or physiologic corticosteroid replacement
therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of
systemic treatment.

- Treatment with surgery or chemotherapy within 21 days prior to study entry (42 days
for nitrosoureas or mitomycin C)

- Treatment with low dose chemotherapy concurrent with radiation within 14 days prior to
study entry

- Treatment with radiation therapy within 14 days prior to study entry

- Treatment with any other investigational agent within 30 days prior to study entry

- Previously treated with an anti-DKK-1 therapy

- Participants who have a history of hypersensitivity reactions to TAXOL® or other drugs
formulated in Cremophor® EL (polyoxyethylated castor oil). Patients who exhibit these
hypersensitivities will be eligible to receive single agent DKN-01.

- Significant allergy to a pharmaceutical therapy that, in the opinion of the
investigator, poses an increased risk to the participant

- Treatment with corticosteroids (≥ 10 mg per day prednisone or equivalent) or other
immune suppressive drugs within the 14 days prior to study entry

- Active substance abuse

- Receipt of any live vaccines within 30 days before the first dose of study treatment
and while participating in the study

- History of (non-infectious) pneumonitis that required steroids or current pneumonitis

- History of interstitial lung disease

- Intolerance or severe hypersensitivity (≥Grade 3) to pembrolizumab and/or of its
excipients