A Phase 2 Study of CTX-009 in Adult Patients with Metastatic Colorectal Cancer who have received Two or Three Prior Systemic Chemotherapy Regimens.

Inclusion Criteria

1. 18 years of age or older

2. Histologically or cytologically confirmed metastatic or recurrent colorectal cancers

3. The primary tumor must have been resected > 3 months prior to planned C1D1.

4. Patients who experienced progressive disease or relapse after receiving two or three

prior lines of systemic therapy in the locally advanced or metastatic setting. Prior

lines of systemic treatment must have included at least one fluoropyrimidine,

oxaliplatin, irinotecan, and bevacizumab containing chemotherapy regimen (in any

combination and may have been administered in the neoadjuvant setting).

1. Patients whose tumor is not right sided and RAS wild type must also have received

an anti-epidermal growth factor receptor (EGFR) therapy.

2. Patients with tumors harboring mutations or other alterations for which there are

available targeted therapies (e.g. BRAF V600E, HER2-positive, MSI-H/dMMR, etc.)

must have also received the relevant approved targeted therapies.

3. If patient received peri-operative treatment (neoadjuvant and/or adjuvant),

please consult the Sponsor Medical Monitor for review of prior treatment lines.

5. At least one lesion measurable as defined by RECIST v1.1

6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

7. Predicted life expectancy of at least 12 weeks

8. Adequate hepatic and renal function within 14 days of C1D1 as described below:

1. Total bilirubin ≤ 1.5 X upper limit of normal (ULN)

2. Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤ 3.0 X ULN (≤

5x ULN in case of hepatic metastasis)

3. Estimated creatinine clearance ≥ 30 mL/min based on Cockcroft-Gault estimated

creatinine clearance

4. Urine protein ≤ 1+ by spot urinalysis (or, if > 1+ then 24 hr urine protein <1.0

g/24 hr)

9. Female patients who are women of childbearing potential (WCBP) must have a negative

pregnancy test (serum-human chorionic gonadotropin [hCG] or urine-hCG) at Screening

within 14 days of C1D1

10. Female patients must be surgically sterile (or have a monogamous partner who is

surgically sterile) or be at least 2 years postmenopausal or commit to use 2

acceptable forms of birth control (defined as the use of an intrauterine device (IUD),

a barrier method with spermicide, condoms, any form of hormonal contraceptives, or

abstinence) for the duration of the study and for 4 months following the last dose of

study treatment. Male patients must be sterile (biologically or surgically) or commit

to the use of a reliable method of birth control (condoms with spermicide) for the

duration of the study and for 4 months following the last dose of study treatment

11. Signed and dated Institutional Review Board (IRB)/Independent Ethics Committee (IEC)

approved Informed Consent Form (ICF) before any protocol-directed screening procedures

are performed

Exclusion Criteria

1. From the time point of signed informed consent,

1. Less than 4 weeks have elapsed since patients had a surgery or major procedure

2. Less than 2 weeks have elapsed from the last treatment date since patients had

any radiation therapy

2. Prior to planned C1D1,

1. Less than 4 weeks have elapsed since patients had chemotherapy or targeted

therapy for colorectal cancer

2. Less than 4 weeks have elapsed since patients had anticancer immunotherapy or

investigational drug treatment

3. A history of the following cardiovascular diseases in past 5 years may be

exclusionary, as determined by the Sponsor Medical Monitor:

1. Congestive heart failure that corresponds to Class II or a higher class under New

York Heart Association (NYHA) classification or less than 50% of left ventricular

ejection fraction (LVEF)

2. Uncontrolled hypertension (systolic blood pressure [SBP]/diastolic blood pressure

[DBP] > 140/90 mmHg) (e.g., patient with SBP/DBP > 140/90 mmHg despite the best

care including anti-hypertensive medications)

3. Patients with a history of hypertensive crisis or pre-existing hypertensive

encephalopathy

4. Pulmonary hypertension

5. Myocardial infarction

6. Uncontrolled arrhythmia

7. Unstable angina

8. Patients with any significant vascular diseases (e.g., aortic aneurysm requiring

surgery or recent peripheral artery thrombosis) within 6 months prior to the

initial treatment of the investigational product

4. Symptomatic or uncontrolled central nervous system (CNS) metastasis (However, patients

with asymptomatic CNS metastasis can participate provided that systemic corticosteroid

treatment was discontinued at least 4 weeks prior to screening and that the patient is

radiologically and neurologically stable or improving)

5. A history of the following hemorrhage-related or gastroenterological disease:

1. Active hemorrhage, hemorrhagic diathesis, coagulopathy or tumor invasion into

great arteries

2. History of clinically significant and active (within 6 months)

gastroenterological disease, such as peptic ulcer, gastrointestinal (GI)

bleeding, GI or non-GI fistula, perforation, abdominal abscess, clinical symptoms

and signs of GI obstruction, need for parenteral hydration or nutrition, or

inflammatory bowel disease.

6. Patients who received antiplatelet drugs (aspirin, clopidogrel, etc.) or anticoagulant

drugs (warfarin, heparin, direct thrombin inhibitors, etc.) within 2 weeks prior to

C1D1, or are expected to need those drugs during the clinical study.

7. Patients requiring continuous treatment with systemic non-steroidal anti-inflammatory

drugs (NSAIDs) or systemic corticosteroids (the following cases are permitted):

1. NSAIDs: Up to 3 consecutive days' use is permitted

2. Corticosteroids: Topical use of corticosteroid, such as topical intra-articular

injection, intranasal administration, eye drops, inhaler, etc., or temporary

systemic corticosteroid use for treatment and prevention of patient's contrast

media allergy, or adverse event, is permitted

8. Severe infection requiring systemic antibiotics, antivirus drugs, etc., or other

uncontrolled acute active infectious diseases

9. Patients with evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV)

infection. Inactive hepatitis B carriers who tested HBsAg positive may enroll provided

that the patient's liver function values are normal. Also, patients with chronic HBV

infection which has been controlled by the site's treatment guideline may enroll. HCV

patients showing sustained viral response or patients with immunity to HBV infection

may enroll

10. Patients with other severe diseases or uncontrolled illnesses that warrant the

exclusion from the study (permitted only if medically controlled) including but not

limited to:

1. Pre-existing hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within

28 days prior to screening

2. Major, unhealed injury, active ulcer or untreated fracture

3. History of cerebrovascular incident (ischemic or hemorrhagic stroke), transient

ischemic attack or subarachnoid hemorrhage within 6 months prior to screening

4. Moderate to severe ascites and/or pleural effusion

11. Clinically significant abnormal electrocardiography (ECG) findings or history

determined as clinically significant by the Investigator

12. QT interval (Fridericia's formula) (QTcF) interval > 450 msec at the time of screening