LY3214996 and Cetuximab Alone or in Combination With Abemaciclib for the Treatment of Unresectable or Metastatic Colorectal Cancer

Exclusion Criteria

• •History of a Grade 3 or 4 allergic reaction or intolerability attributed to cetuximab.
• •Right-sided or transverse colonic primary tumor.
• •Baseline tissue-based KRAS, NRAS, EGFR, BRAF and MEK1 mutated tumor
• •Active infection requiring concurrent antibiotic use.
• •Currently using concomitant medications that are strong inhibitors or inducers of CYP3A4.
• •Previously completed or withdrawn from this study or any other study investigating an ERK1/2 inhibitor.
• •Any known symptomatic brain metastasis. Note: Participants previously treated or untreated for this condition who are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed. Known brain metastases must be stable for ≥ 4 weeks, with imaging (e.g., magnetic resonance imaging \[MRI\] or computed tomography \[CT\]) demonstrating no current evidence of progressive brain metastases at screening.
• •Known leptomeningeal disease
• •Previous or concurrent malignancy within 3 years of study entry, with the following exceptions: adequately treated basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy; other solid tumors treated curatively without evidence of recurrence for at least 3 years prior to study entry.
• •Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
• •* History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) \<6 months prior to screening,
• •* Symptomatic chronic heart failure (i.e. Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality \<6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia;
• •* The participant has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• •Uncontrolled hypertension defined as persistent elevation of systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mm Hg, despite current therapy;
• •The participant has active systemic bacterial infection (requiring intravenous (IV) antibiotics at time of initiating study treatment,) fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C (for example, hepatitis B surface antigen positive.) Screening is not required for enrollment.; Known history of acute or chronic pancreatitis (history of acute pancreatitis with no recurrent events in the prior 24 months are permitted)
• •Impaired gastrointestinal function or disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption).
• •Any other condition that would, in the Investigator's judgment, contraindicate the participants participation in the clinical study due to safety concerns or compliance with clinical study procedures.
• •For participants receiving abemaciclib: The participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• •Major surgery ≤ 6 weeks prior to starting study drug or failure to recover from side effects of such procedure at the discretion of the treating investigator.
• •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• •Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study.