1. Signed written informed consent must be obtained and documented according to
International Conference on Harmonisation (ICH) and local regulatory requirements
2. A histologically or cytologically confirmed cancer that is metastatic, unresectable,
or recurrent and for which treatment with ipilimumab, or nivolumab, or pembrolizumab
is a reasonable therapeutic option in the opinion of the investigator.
3. ≥ 18 years of age
4. Measurable disease as defined by Immune-Related Response Evaluation Criteria in Solid
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Male or female patients of child-producing potential must agree to use contraception
or avoidance of pregnancy measures during the study and for 30 days after the last
7. Females of childbearing potential must have a negative serum pregnancy test
8. Aspartate transaminase (AST) < 2.5 x upper limit of normal (ULN) and alanine
transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN).
9. Hemoglobin (Hgb) ≥ 9 g/dl
10. Total bilirubin ≤ 1.5 × ULN. Patients with liver lesions who do not have
hepatocellular carcinoma and who have a total bilirubin < 2.0 x ULN may be eligible if
agreed upon by the investigator and medical monitor for the sponsor.
11. Creatinine ≤ 1.5 × ULN or, for patients with creatinine levels above institutional
upper limit of normal, creatinine clearance must be > 60 mL/min/1.73 m^2.
12. Absolute neutrophil count ≥ 1.5 x 10^9/L
13. Platelets ≥ 100 x 10^9/L; patients with hepatocellular carcinoma may enroll provided
they have a platelet count ≥ 75 x 10^9/L.
14. Life expectancy ≥ 3 months
1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents
within 7 days of first dose of BBI608. Patients may begin BBI608 on a date determined
by the investigator and medical monitor for the sponsor after a minimum of 7 days
since last receiving anti-cancer treatment, provided that all treatment-related
adverse events (AEs) have resolved or have been deemed irreversible
2. Had a surgical procedure requiring general anesthesia or inpatient hospitalization for
recovery less than 4 weeks prior to beginning protocol therapy.
3. Any known, untreated, brain metastases. Treated subjects must be stable 4 weeks after
completion of treatment for brain metastases and image documented stability is
required. Patients must have no clinical symptoms from brain metastases and have not
required systemic corticosteroids >10 mg/day prednisone or equivalent for at least 2
weeks prior to first dose of study drug.
4. Pregnant or breastfeeding
5. Unable or unwilling to swallow BBI608 capsules daily
6. Significant gastrointestinal disorder(s) (e.g., active Crohn's disease or ulcerative
colitis, or a history of extensive gastric resection and/or small intestinal
resection) such that absorption of oral medications is impaired.
7. Has an active autoimmune disease requiring immunosuppression with the exception of
subjects with isolated vitiligo, resolved childhood asthma or atopic dermatitis,
controlled hypoadrenalism or hypopituitarism, and euthyroid patients with a history of
8. Has interstitial lung disease or active, non-infectious pneumonitis
9. Has a transplanted organ or has undergone allogeneic bone marrow transplant
10. Has received a live vaccine within 30 days prior to first dose.
11. Known hypersensitivity to a component of protocol therapy
12. Uncontrolled concurrent illness including, but not limited to ongoing or active
infection, clinically significant non-healing or healing wounds, symptomatic
congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant
pulmonary disease (shortness of breath at rest or on mild exertion), uncontrolled
infection or psychiatric illness/social situations that would limit compliance with
13. Subjects with a history of another primary cancer, with the exception of: a)
curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma
in situ; c) localized prostate cancer not requiring systemic therapy; and c) other
primary tumors with no known active disease present that, in the opinion of the
investigator and medical monitor for the sponsor, will not affect patient outcome in
the setting of the current diagnosis.
14. Abnormal ECGs that are clinically significant such as QT prolongation (QTc > 480
msec), clinically significant cardiac enlargement or hypertrophy, new bundle branch
block or existing left bundle branch block, or signs of new, active ischemia.