This Phase I trial is trying to determine how safe and tolerable a targeted therapy (BGB-3245) is in people with solid cancers with B-RAF genetic mutations.A First-in-Human, Phase 1a/1b, Open Label, Dose-Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, and Antitumor Activity of the RAF Dimer Inhibitor BGB-3245 in Patients With Advanced or Refractory Tumors

Inclusion

1. Participants with histologically confirmed advanced or metastatic solid tumor who had disease progression during or after systemic anticancer therapies that previously demonstrated clinical benefit (eg, improved survival) in a representative population, or are unable to receive standard therapy(ies). In addition, participants must meet the following eligibility criteria for the corresponding phase of the study:

   1. Phase 1a: participants with a known mutation status and tumor harboring an oncogenic mutation of the v-RAF murine sarcoma viral oncogene homolog B (BRAF) gene (the mutations of primary interest are the BRAF Class II mutation, Class III mutation or BRAF fusion). In addition, participants with tumors harboring the mutation of the neuroblastoma RAS viral oncogene homolog (NRAS) gene or the Kirsten rat sarcoma virus oncogene homolog (KRAS) are eligible for Part 1a. For participants with KRAS mutations, tumor types of colorectal cancer (CRC) and pancreatic cancer are excluded.
   2. Phase 1b: participants must have a known mutation status and meet one of the following criteria according to the group they are enrolled into:

   I. Group 1: participants with tumor types other than CRC that harbor BRAF V600 mutations who have been treated and progressed on prior BRAF and/or mitogen activated protein kinase (MEK) inhibition.

   a. Participants must have received the last dose of prior BRAF and/or MEK inhibitor therapy within 90 days of initiation of BGB-3245 study treatment (Cycle 1 Day 1)

   II. Group 2: participants with advanced solid tumors harboring a BRAF Class II mutation or a BRAF fusion mutation.

2. Participants must provide archival tumor tissue or agree to a fresh tumor biopsy for mutation and biomarkers analysis (fresh tumor biopsies are strongly recommended)
3. Participants must have radiologically measurable disease as defined by RECIST v1.1
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
5. Adequate organ function and no transfusions within 14 days of first dose