A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers

• ClinicalTrials.gov Identifier: NCT02467361
• Recruitment Status: Completed
• First Posted: June 10, 2015
• Last Update Posted: July 21, 2020
• Sponsor: Sumitomo Dainippon Pharma Oncology, Inc
• Information provided by (Responsible Party): Sumitomo Dainippon Pharma Oncology, Inc

Tracking Information

• First Submitted Date: June 4, 2015
• First Posted Date: June 10, 2015
• Last Update Posted Date: July 21, 2020
• Study Start Date: August 2015
• Actual Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 5, 2015)

• Determination of the safety and tolerability of BBI608 administered in combination with selected immunotherapeutic agent by assessing dose-limiting toxicities (DLTs) [ Time Frame: 6 weeks ]
• Determination of the Recommended Phase 2 Dose (RP2D) by assessing dose-limiting toxicities (DLTs) [ Time Frame: 6 weeks ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 5, 2015)

• Assessment of the preliminary anti-tumor activity by performing tumor assessments every 8 weeks (Phase 2 portion) [ Time Frame: 6 months ]
  Evaluation of anti-tumor activity will be performed according to Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST).
• Pharmacokinetic profile of BBI608 administered in combination with the selected immunotherapeutic agent as assessed by maximum plasma concentration and area under the curve [ Time Frame: -5min, 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours on day 1, cycles 1 and 2 ]
• Pharmacodynamic activity of BBI608 administered in combination with the selected immunotherapeutic agent as assessed by biomarker analysis [ Time Frame: 6 months ]
  Histopathology and Cancer Stem Cell assays will be performed to provide information of the biomarkers on biopsied patient tumor tissue, and archival samples.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors in Adult Patients With Advanced Cancers
• Official Title: A Phase Ib/II Clinical Study of BBI608 Administered in Combination With Immune Checkpoint Inhibitors to Adult Patients With Advanced Cancers
• Brief Summary: This is an open label, multi-center, Phase 1/2 study of BBI608 administered in combination with immunotherapy in adult patients with advanced cancers. The goal of the study is to determine the RP2D of BBI608 in combination with each of the immunotherapeutic agents.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cancer

Intervention

• Drug: BBI608
  Patients in this trial will receive BBI608 at assigned dose-levels according to the study arm the patient is enrolled into. BBI608 Dose Level 1: 240 mg twice daily, Dose Level 2: 480 mg twice daily. The assigned dose of BBI608 will be administered twice daily with approximately 12 hours between doses.
  Other Names:

  • Napabucasin
  • BB608
  • BBI-608
• Drug: Ipilimumab
  Ipilimumab 3 mg/kg is administered intravenously over 90 minutes every 21 days for a total of 4 doses.
  Other Name: Yervoy
• Drug: Nivolumab
  Nivolumab 3 mg/kg is administered as an intravenous infusion over 60 minutes every 14 days.
  Other Name: Opdivo
• Drug: Pembrolizumab
  Pembrolizumab 2 mg/kg is administered as an intravenous infusion over 30 minutes once every 21 days.
  Other Name: Keytruda

Study Arms

• Experimental: Combo with Ipilimumab
  Interventions:

  • Drug: BBI608
  • Drug: Ipilimumab
• Experimental: Combo with Nivolumab
  Interventions:

  • Drug: BBI608
  • Drug: Nivolumab
• Experimental: Combo with Pembrolizumab
  Interventions:

  • Drug: BBI608
  • Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 12, 2018): 104
• Original Estimated Enrollment (submitted: June 5, 2015): 120
• Actual Study Completion Date: June 2020
• Actual Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

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 Tumors (irRECIST).
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 dose
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

Exclusion criteria:

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 Grave's disease.
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 study requirements
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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02467361
• Other Study ID Numbers: BBI608-201CIT
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Sumitomo Dainippon Pharma Oncology, Inc
• Study Sponsor: Sumitomo Dainippon Pharma Oncology, Inc
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Sumitomo Dainippon Pharma Oncology, Inc
• Verification Date: July 2020