Early Identification and Treatment of Occult Metastatic Disease in Stage III Colon Cancer

Inclusion Criteria

• PRE-SCREENING: Participants must have histologically confirmed resected stage III adenocarcinoma of colon. Any T [Tx, T1, T2, T3, or T4-], N1-2M0
• PRE-SCREENING: Participants plan to receive or have initiated/received standard adjuvant chemotherapy per the discretion of the treating physician. Standard therapy includes leucovorin calcium (calcium folinate), 5-fluorouracil and oxaliplatin (FOLFOX), capecitabine and oxaliplatin (CAPOX), or therapy with fluorouracil (5FU) analog alone will be permitted if it constitutes appropriate standard therapy in the opinion of the treating physician
• PRE-SCREENING: Participants must have sufficient tumor tissue available for molecular profiling
• PRE-SCREENING: Age >= 18 years
• PRE-SCREENING: Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• PRE-SCREENING: Ability to understand and the willingness to sign a written informed consent document
• PRE-SCREENING: Participants must not have received prior neoadjuvant chemotherapy or immunotherapy
• SCREENING: Participants must have histologically confirmed resected stage III adenocarcinoma of colon. Any T [Tx, T1, T2, T3, or T4-], N1-2M0
• SCREENING: Participants must have completely resected disease. In patients with tumor adherent to adjacent structures, en block RO resection must be documented
• SCREENING: Entire tumor must be in the colon (rectal involvement is excluded)
• SCREENING: Participants must have completed standard adjuvant chemotherapy per the discretion of the treating physician. Standard therapy includes FOLFOX, CAPOX, or therapy with 5FU analog alone will be permitted if it constitutes appropriate standard therapy in the opinion of the treating physician
• SCREENING: Participants must not have received prior neoadjuvant chemotherapy or immunotherapy
• SCREENING: Age ≥ 18 years
• SCREENING: ECOG performance status =< 1
• SCREENING: Life expectancy of greater than 3 months
• SCREENING: Leukocytes >= 3,000/mcL
• SCREENING: Absolute neutrophil count >= 1,500/mcL
• SCREENING: Platelets >= 100,000/ mcL
• SCREENING: Total bilirubin within normal institutional limits. For patients with Gilbert’s syndrome, total bilirubin must be =< 2 and documented as elevated indirect bilirubin
• SCREENING: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) =< 3 and alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional upper limit of normal
• SCREENING: Creatinine =< institutional upper limit of normal OR creatinine clearance >= 40 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal by Cockcroft-Gault formula
• SCREENING: In order to be eligible for the ctDNA positive cohort, women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG])
• SCREENING: The effects on the developing human fetus are unknown. For this reason and because 5FU, capecitabine, oxaliplatin, irinotecan, leucovorin, and cetuximab are known to be teratogenic, in order to be eligible for one of these ctDNA positive cohort, females of child-bearing potential (FOCBP) and males must be willing to abstain from heterosexual activity or use 2 forms of effective contraception (e.g., hormonal or barrier method of birth control with a failure rate of less than 1% per year) from time of informed consent until 5 months (FOCBP) and 7 months (males) after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women who are not of childbearing potential, i.e., who are postmenopausal or surgically sterile as well as azoospermic men, do not require contraception
• SCREENING: Participants must have documentation of microsatellite instability status. Testing by NGS, PCR based assessment and Immunohistochemistry (IHC) are acceptable. Presence of deficient (d) DNA mismatch repair (dMMR) may be assessed by IHC for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicated dMMR. This may be done locally
• SCREENING: Participants circulating tumor DNA (ctDNA) assay (Guardant Health) must satisfy assay specific quality control metrics to generate a result
• SCREENING: In order to be eligible for the ctDNA positive cohort, patient must be ctDNA positive following adjuvant therapy using the Clinical Laboratory Improvement Act (CLIA) certified Guardant Reveal assay. A commercially available Guardant Reveal, trademark, may be used with sponsor investigator review and approval. ctDNA positive will be defined as positive based on having a tumor derived signal in the cfDNA that passes calling threshold (“ctDNA detected”)
• SCREENING: Ability to understand and the willingness to sign a written informed consent document
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Must have documentation of one of the following: * Microsatellite instability status. NGS, PCR based assessment and Immunohistochemistry (IHC) are acceptable. Presence of deficient (d) DNA mismatch repair (dMMR) may be assessed by IHC for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicated dMMR. This may be done locally. OR * Pathogenic mutations in polymerase ε (POLE) or polymerase δ1 (POLD1)
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Patients must have detectable ctDNA (Guardant Reveal assay) post standard adjuvant therapy in order to be in this cohort
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/L (1500/uL) without granulocyte colony-stimulating factor support
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Lymphocyte count ≥ 500/mcL
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Hemoglobin ≥ 90 g/L (9 g/dL; patients may be transfused to meet this criterion
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 x institutional upper limit of normal (ULN)
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Serum albumin ≥ 25 g/L (2.5 g/dL)
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: For patients not receiving therapeutic anticoagulation: International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 x institutional ULN
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Participants receiving therapeutic anticoagulation must have a stable anticoagulant regimen
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Negative HIV test at screening; patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/mcL and have an undetectable viral load
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Negative hepatitis B surface antigen (HBsAg) test at screening
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening; The HCV RNA test must be performed for patients who have a positive HCV antibody test
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Because atezolizumab is not recommended during pregnancy in most circumstances, females of child-bearing potential (FOCBP) must be willing to abstain from heterosexual activity or use 2 forms of effective contraception (e.g., hormonal or barrier method of birth control with a failure rate of less than 1% per year) from time of informed consent until 5 months after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. Women who are not of childbearing potential, i.e., who are postmenopausal or surgically sterile, do not require contraception
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Females of childbearing potential must agree to refrain from donating eggs from time of informed consent until 5 months after the last dose of study treatment
• ATEZOLIZUMAB SPECIFIC INCLUSION CRITERIA FOR MSI-H/POLE/POL-D COHORT: Patients requiring pain medication must be on a stable regimen at the time of registration
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC INCLUSION CRITERIA FOR BRAF MUTANT COHORT: Presence of BRAFV600E in tumor tissue previously determined mutational testing at any time prior to screening
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC INCLUSION CRITERIA FOR BRAF MUTANT COHORT: Participants must have detectable ctDNA (Guardant Reveal assay) post standard adjuvant therapy in order to be in this cohort
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC INCLUSION CRITERIA FOR BRAF MUTANT COHORT: Hemoglobin >= 9 g/dL (5.58 mmol/L)
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC INCLUSION CRITERIA FOR BRAF MUTANT COHORT: Total bilirubin =< 1.5 (25.65 umol/L)
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC INCLUSION CRITERIA FOR BRAF MUTANT COHORT: Platelets >= 100,000/uL
• TRASTUZUMAB AND PERTUZUMAB SPECIFIC INCLUSION CRITERIA FOR HER2 COHORT: HER2 overexpression/amplification as shown by NGS sequencing, IHC/FISH or Tumor with 3+ by IHC or 2+ by IHC and HER2/cep17 ratio > 2 by FISH
• TRASTUZUMAB AND PERTUZUMAB SPECIFIC INCLUSION CRITERIA FOR HER2 COHORT: AST(SGOT) =< 1.25 and ALT(SGPT) =< 1.25 × institutional upper limit of normal
• TRASTUZUMAB AND PERTUZUMAB SPECIFIC INCLUSION CRITERIA FOR HER2 COHORT: For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs, as defined below: * Females must remain abstinent or use non-hormonal contraceptive methods with a failure rate of < 1% per year, or 2 effective non-hormonal contraceptive methods during the study treatment period participants of childbearing potential must use effective contraceptive methods during and for 7 months after the last dose of HER2-targeted therapy. Women must refrain from donating eggs during this same period
• TRASTUZUMAB AND PERTUZUMAB SPECIFIC INCLUSION CRITERIA FOR HER2 COHORT: Males must agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the study treatment periods and for 7 months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period
• TRASTUZUMAB AND PERTUZUMAB SPECIFIC INCLUSION CRITERIA FOR HER2 COHORT: History of other malignancies within the 5 years prior to study registration, except for the following: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin (malignancies occurring more than 5 years prior to study entry are permitted if curatively treated with surgery alone)
• TRASTUZUMAB AND PERTUZUMAB SPECIFIC INCLUSION CRITERIA FOR HER2 COHORT: LVEF >= 55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) within 12 weeks of treatment start.

Exclusion Criteria

• Patients who are receiving additional investigational therapy or on another investigational protocol
• Patients who have confirmed metastatic disease per imaging
• Patients who are unable to get any standard adjuvant therapy
• Patients who have received more than 6 months of standard adjuvant therapy at the time of study entry
• With the exception of standard of care adjuvant therapy, patient received anticancer therapy including chemotherapy, immunotherapy, or antineoplastic biologic therapy (e.g., cetuximab, bevacizumab etc.), within 30 days prior to start of study treatment
• Patients who are MSI-high or have a BRAF V600E mutation are excluded from Arm 1 (FOLFIRI)
• Patients with a BRAFV600E mutation and who are MSI-high are excluded from Arm 5 (encorafenib [ENCO]/binimetinib [BINI]/cetuximab [CETUX])
• Has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 6 months for woman and 6 months for men, after the last dose of trial treatment. (ctDNA positive cohort only).
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has an active infection requiring systemic therapy
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Has active or history of immune deficiency or is receiving systemic steroid therapy or any other forms of immunosuppressive therapy within 2 weeks prior to the first dose of atezolizumab treatment. Subject requiring systemic steroids or anticipated need for systemic immunosuppressive medication during study treatment are excluded from the trial. The use of physiologic doses of corticosteroids may be approved after discussion with the sponsor. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study * Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Has active or history of autoimmune disease with the following exceptions: * Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study * Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study * Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: ** Rash must cover < 10% of body surface area ** Disease is well controlled at baseline and requires only low-potency topical corticosteroids ** There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Has any of the following conditions: * Uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage ( ≥ monthly). Patients with indwelling catheters are allowed * Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12mg/dL or corrected serum calcium > institutional ULN * Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at study entry
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: History of leptomeningeal disease
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Has active or a known history of active TB (Bacillus tuberculosis)
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Hypersensitivity to atezolizumab or any of its excipients
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Has significant cardiovascular disease (such as New York Heart Association class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Has had a major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could impact patient safety
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Patients that require supplemental oxygen are excluded
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Prior allogeneic stem cell or solid organ transplantation
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment; patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Current treatment with anti-viral therapy for HBV
• ATEZOLIZUMAB SPECIFIC EXCLUSION CRITERIA FOR MSI-H/POL-D COHORT: Has received a live vaccine within 4 weeks of planned start of study therapy, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab * Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Patients with a BRAFV600E mutation and who are MSI-H are excluded from Arm 5 (ENCO/BINI/CETUX)
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Prior therapy with a BRAF inhibitor (e.g., encorafenib, dabrafenib, vemurafenib) and/or a MEK inhibitor (e.g., binimetinib, trametinib, cobimetinib)
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Known hypersensitivity or contraindication to any component of binimetinib or encorafenib or their excipients
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: The patient has a history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab, or has red meat allergy or tick bite history
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Inability to swallow and retain study drug
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Patients who have undergone major surgery (e.g., in-patient procedures) =< 6 weeks prior to start of study treatment or who have not recovered from side effects of such procedure
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Patients who have had radiotherapy =< 14 days prior to start of study treatment or who have not recovered from side effects of such procedure. * Note: Palliative radiation therapy must be complete 7 days prior to the first dose of study treatment
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Patient has not recovered to =< Grade 1 from toxic effects of prior therapy before starting study treatment. * Note: Stable chronic conditions (=< Grade 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies) are exceptions and may enroll
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, any of the following: * History of myocardial infarction < 12 months of screening or history of other acute coronary syndromes (including unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) < 6 months prior to Screening; * Congestive heart failure requiring treatment (New York Heart Association class >= 2); * History of documented heart failure or systolic dysfunction (left ventricular ejection fraction [LVEF] <50%); * Uncontrolled hypertension defined as persistent systolic blood pressure >= 150 mmHg or diastolic blood pressure >= 100 mmHg despite current therapy; * History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia); * Baseline corrected QT (QTc) interval >= 480 ms
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Impairment of gastrointestinal function or disease which may significantly alter the absorption of study drug (e.g., active ulcerative disease, uncontrolled vomiting or diarrhea, malabsorption syndrome, small bowel resection with decreased intestinal absorption), or recent (=< 3 months) history of a partial or complete bowel obstruction, or other conditions that will interfere significantly with the absorption of oral drugs
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Known history of acute or chronic pancreatitis
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Concurrent neuromuscular disorder that is associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Current use of a prohibited medication (including herbal medications, supplements, or foods), or use of a prohibited medication =< 1 week prior to the start of study treatment
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: History of thromboembolic or cerebrovascular events =< 12 weeks prior to the first dose of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli * Note: Patients with either deep vein thrombosis or pulmonary emboli that does not result in hemodynamic instability are allowed to enroll as long as they are on a stable dose of anticoagulants for at least 4 weeks * Note: Patients with thromboembolic events related to indwelling catheters or other procedures may be enrolled
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Concurrent or previous other malignancy within 2 years of study entry, except adequately treated basal or squamous cell skin cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, Bowen’s disease and Gleason 6 prostate cancer
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• ENCORAFENIB, BINIMETINIB, AND CETUXIMAB SPECIFIC EXCLUSION CRITERIA FOR BRAF MUTANT COHORT: Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection * Note: Patients with laboratory evidence of cleared HBV or HCV infection may be enrolled * Note: Patients with no prior history of HBV infection who have been vaccinated against HBV and who have a positive antibody against hepatitis B surface antigen as the only evidence of prior exposure may be enrolled
• TRASTUZUMAB AND PERTUZUMAB SPECIFIC EXCLUSION CRITERIA FOR HER2 COHORT: Serious cardiac illness or medical conditions including but not confined to: * History of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 Grade >= 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class >= II * High-risk uncontrolled arrhythmias ie, atrial tachycardia with a heart rate >= 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block (second degree AV-block Type 2 [Mobitz 2] or third degree AV-block) * Serious cardiac arrhythmia or severe conduction abnormality not controlled by adequate medication * Angina pectoris requiring anti-anginal medication. * Evidence of myocardial infarction within 12 months prior to enrollment * Clinically significant valvular heart disease * Evidence of transmural infarction on electrocardiogram (ECG) * Poorly controlled hypertension (eg, systolic > 180 mm Hg or diastolic >100 mm Hg). * History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction [LVSD], left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia,hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
• TRASTUZUMAB AND PERTUZUMAB SPECIFIC EXCLUSION CRITERIA FOR HER2 COHORT: High risk patients who have received chemoprevention drugs in the past are not allowed to enroll in the study
• TRASTUZUMAB AND PERTUZUMAB SPECIFIC EXCLUSION CRITERIA FOR HER2 COHORT: Concurrent anti-cancer treatment in another investigational trial, including hormone therapy, bisphosphonate therapy and immunotherapy
• TRASTUZUMAB AND PERTUZUMAB SPECIFIC EXCLUSION CRITERIA FOR HER2 COHORT: Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness (e.g., infections or poorly controlled diabetes)