A Study of VS-6766 and Cetuximab in Patients With Advanced Colorectal Cancer

Exclusion Criteria

• •Participants with uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring systemic treatment, symptomatic congestive heart failure, cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements, hypertension, defined as systolic blood pressure \> 160 mmHg despite medical management, myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting \< 12 months prior to screening.
• •Participants with clinically relevant coronary artery disease or history of myocardial infarction in last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency, or those with uncontrolled or poorly controlled hypertension (\>180 millimeters of mercury (mmHg) systolic or \>130 mmHG diastolic pressures) may not receive cetuximab.
• •Participants with history of corrected QT interval (QTc) prolongation, Brugada syndrome, known history of QTc prolongation, or Torsades de Pointes.
• •Participants with known COVID-19 infection within 28 days prior to first dose of therapy are excluded. History of Gilbert's syndrome.
• •Participants with history of recent rhabdomyolysis within last 3 months.
• •Participants with active skin disorder that has requested systemic therapy within past 12 months.
• •Participants with a history of neuromuscular disorders that are associated with elevated creatine phosphokinase (CPK) (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
• •History of other malignancy which could affect compliance with the protocol or interpretation of results.
• •History of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are allowed. Subjects with a malignancy that has been treated with curative intent will also be allowed if the malignancy has been in remission without treatment for ≥ 2 years prior to Cycle 1, Day 1. Subjects with localized prostate cancer that has been treated with curative intent will be allowed.
• •Participants planning to embark on a new strenuous exercise regimen after the first dose of study treatment (e.g. running or bicycling \> 10 mph) due to risk of CPK elevation.
• •Participants with history of a malabsorption syndrome or uncontrolled nausea, vomiting, or diarrhea that may interfere with the absorption of oral study medication in the opinion of the treating study doctor.
• •Participants with evidence of visible retinal pathology or retinal degenerative disease on screening ophthalmologic examination that places the participant at an unacceptable risk for ocular events. Related to their vision and eye health, patients must also:
• •* Not have history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes.
• •* Not have history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO
• •* Patients must not have history of corneal erosion (instability of corneal epithelium), corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions.
• •* Patients must not have history of retinal degenerative disease.
• •* Patient must not have presence of neurosensory retinal detachment, or neovascular macular degeneration on screening ophthalmologic exam.
• •Patients with Impairment of gastrointestinal function or gastrointestinal disease (e.g., active ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) are excluded.
• •Participants should not have history of bowel perforation or intestinal fistulas in the last 6 months.
• •Participants with current Grade 3 or higher neuropathy are excluded.
• •No prior allogeneic stem cell or solid organ transplantation. Patients may not have had prior stem cell or solid organ transplantation. Women who are pregnant or breastfeeding are excluded.
• •History of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab, or if the patient had red meat allergy/tick bite history.
• •The participant is on any medications that conflict with the drugs administered in study.
• •Participants with known or suspected allergy or hypersensitivity to VS-6766 or any of the inactive ingredients which include, but is not limited to, hydroxypropylmethylcellulose, mannitol, magnesium stearate.
• •If the participant has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab, or if the participant had red meat allergy/tick bite history they must be excluded.
• •Chronic concomitant treatment with strong inhibitors of Cytochrome P450 3A4 (CYP3A4) is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study. See Section 8.1.9 for more information.
• •Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.
• •Participants must avoid grapefruit, grapefruit juice, St. John's Wort and other medications (with or without prescriptions), supplements, herbal remedies or foods that are strong inhibitors or inducers of CYP3A4 while on VS-6766.