Study to Evaluate the Efficacy and Safety of Cetuximab in Combination with Encorafenib Plus Binimetinib As Induction Treatment in BRAF V600E Mutated MSS Initially Resectable or Potentially Resectable Advanced Colorectal Cancer

1\. Any medical or psychiatric condition including recent (within the past year) or current suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

2\. Leptomeningeal disease or brain metastases. 3. History of chronic inflammatory bowel disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to the start of study treatment.

4\. Known RAS-mutant colorectal adenocarcinoma. 5. Impaired gastrointestinal function (e.g., uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, small bowel resection) or disease which may significantly alter the absorption of oral study intervention or recent changes in bowel function suggesting current or impending bowel obstruction.

6\. Clinically significant cardiovascular diseases, including any of the following:

1. History of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft, coronary angioplasty or stenting) ≤6 months prior to the start of study treatment.

2. Congestive heart failure requiring treatment (New York Heart Association Grade ≥2).

3. History or presence of clinically significant cardiac arrhythmias (including uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia).

4. History of thromboembolic or cerebrovascular events ≤12 weeks prior to the start 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 1: Participants with either deep vein thrombosis or pulmonary emboli that do not result in hemodynamic instability are allowed to enroll as long as they have been on a stable dose of anticoagulants for at least 4 weeks.

Note 2: Participants with thromboembolic events related to indwelling catheters (including PICC lines) or other procedures may be enrolled.

5. Triplicate average QTcF interval ≥480 ms or a history of prolonged QT syndrome.

6. Congenital LQTS. 7. Evidence of active non-infectious pneumonitis. 8. Evidence of active and uncontrolled bacterial or viral infection, with certain exceptions, as noted below, for chronic infection with HIV, hepatitis B or hepatitis C (please see below), within 2 weeks prior to start of study treatment.

9\. Participants positive for HIV are ineligible unless they meet all of the following:

1. A stable regimen of highly active anti-retroviral therapy that is not contraindicated.

2. No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections.

3. A CD4 count \>250 cells/mcL, and an undetectable HIV viral load on standard PCR-based tests.

10\. Active hepatitis B or hepatitis C infection

a. Active HBV is defined as any of the following:

1. HBsAg (+), HBV DNA \>200 IU/mL (105 copies/mL);

2. HBsAg (+), HBV DNA ≤200 IU/mL and persistent or intermittent elevation of ALT/AST and/or liver biopsy showing chronic hepatitis with moderate or severe necroinflammation.

Note: Participants who are HBsAg (-), HBcAb (+) are eligible and should be monitored/treated as per local standard of care.

b. Active HCV is defined as:

1. HCV antibody positive; AND

2. Presence of HCV RNA. 11. Concurrent or previous other malignancy within 3 years of study entry, except curatively treated basal or squamous cell skin cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, Bowen's disease or prostate cancer with a Gleason score ≤6. Participants with other curatively treated malignancies with low risk of recurrence not listed may also be considered eligible after review and approval by the medical monitor.

12\. Residual CTCAE≥ Grade 2 toxicity from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 neuropathy.

13\. Previous treatment with any selective BRAF inhibitor (e.g., encorafenib, dabrafenib, vemurafenib, XL281/BMS-908662) and/or any selective MEK inhibitor prior to screening.

14\. Use of any prohibited medication (including herbal medication), supplement or food that is a moderate or strong inhibitor or inducer of CYP3A4/5 ≤1 week prior to the start of study intervention.

15\. Major surgery (e.g., inpatient procedure with regional or general anesthesia) or completion of radiation therapy ≤4 weeks prior to the start of study treatment.

16\. Previous systemic anticancer therapy for CRC, with the following exceptions:

• Patients with resected (R0 or R1 resections) metastasis of CRC treated with or without adjuvant or neoadjuvant chemotherapy (+/- antiEGFR or bevacizumab) would be includible if the time from the resection or from the end of the adjuvant treatment (the later) to the relapse of CRC were longer than 6 months

What this study is about