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

Open to people ages 18 years and up

1. Able to provide informed consent
2. 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
3. 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.
4. Must have archival tumor tissue or agree to tumor biopsy
5. Measurable disease per RECIST 1.1
6. Eastern Cooperative Oncology Group performance status of less than or equal to 1
7. Life expectancy is greater than 12 weeks of the signing of ICF.
8. Adequate organ function and no transfusion within 14 days of first dose.

9. Females are of non-child bearing potential or willing to use contraception.

   10. Males vasectomized or agree to use contraception.

1. Central Nervous System metastasis
2. Any retinal pathology considered to be a risk factor for central serous retinopathy
3. History of glaucoma
4. Active parathyroid disorder or history of malignancy associated hypercalcemia
5. Clinically significant cardiac disease within the past 6 months of signing ICF.
6. LVEF less than 50%
7. Abnormal QT interval at Screening
8. Severe uncontrolled systemic disease

9. HIV

   10. Clinically significant active or known history of liver disease. (Hepatitis B and

   Hepatitis C)

   11. Hemorrhage or bleeding event at NCI-CTCAE v5.0 Grade 3 or higher within 28 days of

   first dose.

   12. history of or ongoing Von Willebrand disease and/or other past or present bleeding

   disorders

   13. Increased serum calcium 14. Inability to swallow oral medications 15. 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

   16. Concomitant systemic or glucocorticoid therapy within 2 weeks 17. Major surgical procedure or significant traumatic injury within 4 weeks prior to first

   dose or anticipates need for major surgery while on study

   18. Concomitant medicines that are strong CYP3A inhibitors 19. History of toxicity from another RAF, MEK, ERK inhibitor requiring discontinuation of

   treatment from these drugs

   20. Underlying medical conditions in investigator's opinion to be unfavorable to be a part

   of the study

   21. 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.