CGX1321 in Subjects With Advanced Solid Tumors and CGX1321 With Pembrolizumab in Subjects With Advanced GI Tumors (Keynote 596)

The purpose of the Dose Escalation Phase is to examine the safety and determine the maximum
tolerated dose of CGX1321 when administered to subjects with advanced solid tumors.

The purpose of the Dose Expansion Phase and Phase 1b is to continue to examine the safety and
confirm the final Phase 2 dose of CGX1321 alone in subjects with advanced GI tumors (Dose
Expansion Phase) and evaluate the safety and tolerability of CGX1321 in combination with
pembrolizumab in subjects with colorectal tumors (Phase 1b)

Inclusion Criteria:

- Pathologically-confirmed, locally advanced or metastatic solid tumors that have
relapsed or are refractory to or are not considered medically suitable to receive
standard of care treatment (Dose Escalation Phase)

- Histologically-diagnosed, advanced Gl tumors that have relapsed or are refractory to
or are not considered medically suitable to receive standard of care treatment (Dose
Expansion Phase)

- Histologically-diagnosed advanced colorectal tumors that have relapsed or are
refractory to or are not considered medically suitable to receive standard of care
treatment (Phase 1b)

- Radiologically measurable disease

- Minimum life expectancy of 3 months

- Age 18 years or older

- Adequate organ function

- Recovery from prior treatment-related toxicities

Exclusion Criteria:

- Prior exposure to a WNT inhibitor

- Prior exposure to an anti-PD-1, anti-PD-L1 or anti-PD-L2

- Received previous therapy for malignancy within 21 days

- Major surgery within 4 weeks of first dose of study drug

- Radiotherapy within 2 weeks of first dose of study drug

- Significant GI or variceal bleeding or subdural hematoma within 3 months of the first
dose of study drug

- Known active central nervous system metastases and/or carcinomatous meningitis

- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
form of immunosuppressive therapy within 7 days prior to the first dose of study
treatment.

- Currently receiving medications known to be inhibitors of CYP3A4/5. Subjects currently
receiving medications of known inducers of CYP3A4/5 or substrates of CYP2C8/9 and
CYP1A2 may be excluded.

- Osteoporosis (T-score of less than -2.5 by DEXA scan)

- Bone metastases with prior history of pathologic fracture, lytic lesions requiring an
orthopedic intervention, or not receiving bisphosphonates or denosumab

- History of significant cardiac disease or uncontrolled hypertension

- Known history of human immunodeficiency virus (HIV)

- Known active hepatitis A, B or C

- Known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma that has
undergone potentially curative therapy or in situ cervical cancer

- Active systemic infection requiring intravenous antibiotics within 2 weeks of
treatment start

- Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the study

- Pregnancy or lactation