Study of the Safety and Pharmacokinetics of BGB-283 (Lifirafenib) and PD-0325901 (Mirdametinib) in Participants With Advanced or Refractory Solid Tumors

Key Inclusion Criteria:

• Able to provide informed consent
• Age 18 on day of signing informed consent form (ICF) or of the legal age of consent in the jurisdiction in which the study is taking place
• Advanced or metastatic, unresectable tumors (other than patients with tumors of the brain or central nervous system) who have experienced disease progression

• Part A: NSCLC, CRC, ovarian cancer, endometrial cancer, thyroid cancer, melanoma, pancreatic cancer, and other)
• Part B: NRAS mutated solid tumors must have a known mutation status and a histologically or cytologically confirmed advanced or refractory solid tumor. Up to 40% Melanoma and Up to 20% CRC.
• Must have archival tumor tissue or agree to tumor biopsy
• Measurable disease per RECIST 1.1
• Eastern Cooperative Oncology Group performance status of less than or equal to 1
• Life expectancy is greater than 12 weeks of the signing of ICF.
• Adequate organ function and no transfusion within 14 days of first dose.
• Females are of non-child bearing potential or willing to use contraception.
• Males vasectomized or agree to use contraception.

Key Exclusion Criteria:

• Central Nervous System metastasis
• Any retinal pathology considered to be a risk factor for central serous retinopathy
• History of glaucoma
• Active parathyroid disorder or history of malignancy associated hypercalcemia
• Clinically significant cardiac disease within the past 6 months of signing ICF.
• LVEF less than 50%
• Abnormal QT interval at Screening
• Severe uncontrolled systemic disease
• HIV
• Clinically significant active or known history of liver disease. (Hepatitis B and Hepatitis C)
• Hemorrhage or bleeding event at NCI-CTCAE v5.0 Grade 3 or higher within 28 days of first dose.
• history of or ongoing Von Willebrand disease and/or other past or present bleeding disorders
• Increased serum calcium
• Inability to swallow oral medications
• Ongoing radiation therapy or radio-cytotoxic therapy within prior 4 weeks. No chemotherapy, immunotherapy, biologic therapy, hormonal, or molecular targeted therapy within prior 2 weeks
• Concomitant systemic or glucocorticoid therapy within 2 weeks
• Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose or anticipates need for major surgery while on study
• Concomitant medicines that are strong CYP3A inhibitors
• History of toxicity from another RAF, MEK, ERK inhibitor requiring discontinuation of treatment from these drugs
• Underlying medical conditions in investigator's opinion to be unfavorable to be a part of the study
• Has been administered a live vaccine within 4 weeks (28 days) of initiation of study treatment. NOTE: injectable seasonal vaccines for influenza and COVID-19 are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.