Patient case: 14-year-old female with Li-Fraumeni syndrome; genetic feature: TP53

Clinical trial: Special Combination of BBI608 and Pembrolizumab

Summary: the efficacy and safety of BBI608 in combination with pembrolizumab

Detailed description: This is a multicenter, open-label Phase Ib/II study to exploratively evaluate the efficacy and safety of BBI608 in combination with pembrolizumab in patients with metastatic colorectal cancer (CRC) not responded to or intolerant of standard chemotherapy.

Eligibility: Inclusion Criteria
  1. Patients who personally provided written consent to be the subjects of the study
  2. Age of 20 years or older on the day of informed consent
  3. [Phase Ib] Histologically confirmed gastrointestinal cancer [Phase II] Histologically confirmed colon or rectal cancer that is adenocarcinoma , and identification of at least the KRAS codon 12 and 13 mutation status determined by RAS gene testing. Confirmation of the microsatellite instability (MSI) status.
  4. [Phase Ib] Gastrointestinal cancer not responded to or intolerant of standard chemotherapy [Phase II]A history of treatment with one or more regimens of the following standard chemotherapies for metastatic CRC, and being not responded to or tolerated the chemotherapies
  5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1
  6. Patients with evaluable lesions (Cohort A in Phase II and Phase Ib) or measurable lesions (Cohort B in Phase II) specified in the RECIST version 1.1
  7. Patients with adequate organ function based on the following laboratory values measured within 7 days before enrollment
  8. Women of childbearing potential who are negative in a pregnancy test within 7 days before enrollment. Both male and female patients who consent to practice appropriate contraception during the study and for 4 months after the discontinuation of the protocol treatment
  9. Patients with an expected survival of at least 3 months
  Exclusion criteria
  1. Patients who received chemotherapy, molecular-targeted agents and/or palliative radiotherapy within 2 weeks before the start of the protocol treatment or have not recovered from toxicity caused by previous treatment
  2. Patients who underwent general anesthesia, surgery requiring hospitalization and extensive radiotherapy within 4 weeks before the start of the protocol treatment or minor surgery such as implantation of a central venous access device within two weeks before the start of the protocol treatment
  3. Patients with active central nervous system metastases or carcinomatous meningitis.
  4. Pregnant or lactating women
  5. Patients who are unable or not willing to take BBI608 capsules every day
  6. Patients with gastrointestinal disease markedly interfering with the absorption of oral formulations as judged by the investigator
  7. Patients with active autoimmune disease requiring systemic treatment within 2 years before the start of the protocol treatment.
  8. Patients with a history or signs of interstitial lung disease or active non-infectious pneumonitis
  9. Patients who underwent organ or bone marrow transplantation
  10. Patients who received a live vaccine within 30 days before the start of the protocol treatment
  11. Patients who participated in another clinical study within 4 weeks before the start of the protocol treatment and used or using an investigational drug or device
  12. Patients who previously received immunotherapy with drugs targeting PD-1, PD-L1 and/or PD-L2 or BBI608 therapy, or took part in a clinical study of pembrolizumab or BBI608
  13. Patients with uncontrollable complications
  14. Patients with a history of other malignancies within 3 years before the start of the protocol treatment.
  15. Patients with clinically significant Electrocardiogram (ECG) abnormalities
  16. Patients with a history of Human Immunodeficiency Virus (HIV)
  17. Patients with active hepatitis B or C

Relevance to patient case: not relevant