A Phase 3 Study to Evaluate Xilonix as an Anticancer Therapy in Patients With Symptomatic Colorectal Cancer

Inclusion Criteria:

1. Subjects with pathologically confirmed colorectal carcinoma that is metastatic or unresectable and which is refractory to standard therapy. To be considered refractory, a subject must have failed both an oxaliplatin (oxaliplatin may have been in the adjuvant setting) and an irinotecan based regimen.

2. Symptomatic Disease: One symptom from each domain (metabolic and functional) must be present.

   • Evidence of metabolic dysfunction, defined as the presence of one or more of the following:
   • Any degree (up to 20%) of unintentional total body weight loss in the previous 6 months
   • Serum Interleukin 6 levels ≥10 pg/ml
   • Evidence of reduced function or presence of cancer related symptoms as determined by EORTC QLQ-C30.
   • Appetite reduction, with a score of >10
   • Presence of fatigue, with a score of >10
   • Presence of Pain, with a score of >10
   • Decreased Role, Emotional and Social function, with a score of < 90.
3. Eastern Cooperative Oncology Group (ECOG) performance status 1 or 2.

Exclusion Criteria:

1. Mechanical obstruction that would prevent adequate oral nutritional intake.
2. >20% total body weight loss in the previous 6 months.
3. Serious uncontrolled medical disorder, or active infection, that would impair the ability of the patient to receive protocol therapy.

4. Uncontrolled or significant cardiovascular disease, including:

   • A myocardial infarction within the past 6 months.
   • Uncontrolled angina within the past 3 months.
   • Congestive heart failure within the past 3 months, if defined as NYHC-II.
   • Diagnosed or suspected congenital long QT syndrome.
   • Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, Wolff-Parkinson-White (WPW) syndrome, or torsade de pointes).
   • Any history of second or third degree heart block (may be eligible if currently have a pacemaker).
   • Heart rate < 50 beats per minute on pre-entry electrocardiogram.
   • Uncontrolled hypertension (blood pressure >150 mm Hg systolic and >95 mm Hg diastolic).
5. Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.
6. Subjects who have not recovered from the adverse effects of prior therapy at the time of enrollment to ≤ grade 1; excluding alopecia and grade 2 neuropathy.
7. Subjects who have received extensive prior radiation therapy to the bone marrow. Extensive radiation therapy is defined as treatment of more than one axial bony metastasis. However for subjects with rectal cancer pelvic irradiation, in addition to treatment of one axial bony metastasis, is acceptable.
8. Immunocompromised subjects, including subjects known to be infected with human immunodeficiency virus (HIV).
9. Known hepatitis B surface antigen and/or hepatitis C antibody or known history of infection.
10. History of tuberculosis (latent or active) or positive Interferon-gamma release assay (IGRA).
11. Receipt of a live (attenuated) vaccine within 1 month prior to Randomization
12. Subjects with history of hypersensitivity to compounds of similar chemical or biologic composition to Xilonix™ or any component of its formulations.
13. Women who are pregnant or breastfeeding.
14. WOCBP or men whose sexual partners are WOCBP who are unwilling or unable to use an acceptable method of contraception for at least 1 month prior to randomization, for the duration of the study, and for at least 3 months after the last dose of study medication.
15. History of progressive multifocal leukoencephalopathy or other demyelinating disease.
16. Subjects on immunosuppressive therapy, including transplant patients.
17. Subjects with known brain metastases. Subjects with symptoms of brain metastases during screening should undergo CT imaging prior to randomization.