Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

Clinical trial: Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations

Summary: Infigratinib is an oral medication which selectively binds to fibroblast grown factor receptor (FGFR)-2 and is being developed to treat participants with FGFR-2 mutated cholangiocarcinoma. The purpose of the study is to evaluate the efficacy and safety of the investigational agent oral Infigratinib vs standard of care chemotherapy (gemcitabine plus cisplatin) in first-line treatment of participants with unresectable or metastatic cholangiocarcinoma with FGFR-2 gene fusions/translocations.


Eligibility: Inclusion Criteria:
  -  Histologically or cytologically confirmed non-resectable, recurrent or metastatic cholangiocarcinoma. Participants with gallbladder cancer or ampulla of Vater carcinoma are not eligible
  -  Documented FGFR-2 gene fusions/translocations
  -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  -  Able to swallow and retain oral medication
  -  Willingness to avoid pregnancy or father children
  Exclusion Criteria:
  -  Received treatment with any systemic anti-cancer therapy for unresectable, recurrent, or metastatic cholangiocarcinoma. Prior neoadjuvant or adjuvant therapy is permitted if completed > 6 months prior to first dose of study drug.
  -  History of a liver transplant
  -  Received prior or current treatment with a mitogen activated protein kinase kinase (MEK) or selective FGFR inhibitor
  -  Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (such as, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection.
  -  Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc.
  -  History and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vascular system and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification
  -  Current evidence of corneal or retinal disorder/keratopathy
  -  Receiving and continued treatment with agents or consuming foods that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration
  -  Receiving and continued treatment with therapeutic doses of certain anticoagulants that are primarily metabolized by CYP3A4. (Alternative medications that are not metabolized by CYP3A4 (e.g., dabigatran, edoxaban) are allowed)
  -  Clinically significant or uncontrolled cardiac disease
  -  Recent (≤ 3 months prior to first dose of study drug) transient ischemic attack or stroke
  -  Severe hearing loss
  -  Severe neuropathy
  -  History of another primary malignancy within 3 years except adequately treated in-situ carcinoma of the cervix or non-melanoma skin cancer or other curatively treated malignancy that is not expected to require treatment
  -  Pregnant or breastfeeding
  -  Have known microsatellite instability-high (MSI-H) disease and the decision is made by the treating investigator that an alternative, non-study therapy is warranted according to standard of care.

Relevance to patient case: not relevant