Metastatic Colorectal Cancer
Conditions
Brief 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.The same analysis will be performed for the additional cohort to the Phase II part, consisting of patients with metastatic CMS 1 or 4, MMS, CRC not responsive to or intolerant of standard chemotherapy.
Interventions
DRUGNapabucasin
1 cycle is 21days. BBI608: Oral administration at a dose of 240mg or 480 mg twice daily (BID), every day. \[Additional cohort to the Phase II part\] Oral administration at a dose of 240mg mg BID, every day The therapy will be repeated until meeting the discontinuation criteria.
DRUGPembrolizumab
1 cycle is 21days. Pembrolizumab: Administration at a dose of 200 mg/body on Day 1 of each cycle \[Additional cohort to the Phase II part\] Administration at a dose of 200 mg/body on Day 1 of each cycle. The therapy will be repeated until meeting the discontinuation criteria.
Sponsors
Sumitomo Pharma Co., Ltd.
Takayuki Yoshino
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
\[Phase Ib\] 6 to 9 patients \[Phase II\] Cohort A (MSI-H): 10 patients Cohort B (MSS): 40 patients Including patients with metastatic CRC treated at the recommended dose (RD) level in the Phase Ib part who meet criteria for the full analysis set (FAS) \[Additional cohort to the Phase II part\] 1. st stage: CMS 1 or 4, MSS right-side colon cancers\*: 10 patients 2. nd stage: 1. : If no patient shows a partial or complete response in the 1st stage, the study will be prematurely terminated. 2. : If 1 or 2 patients show a partial or complete response in the 1st stage, 19 patients with CMS 1 or 4, MSS right-side colon cancers will be enrolled additionally. 3. : If 3 or more patients show a partial or complete response in the 1st stage, 19 patients with CMS 1 or 4, MSS right-side colon cancers and 10 patients with CMS 1 or 4, MSS left-side colon cancers\* will be enrolled additionally.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For the additional cohort to the Phase II part, screening tests will be performed to identify CMS 1 or 4 and MSS before obtaining informed consent. Patients, who meet all of the following inclusion criteria and none of the
Exclusion criteria
, are eligible for enrollment in the study. 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. \[Additional cohort to the Phase II part\] Histologically confirmed colon or rectal cancer that is adenocarcinoma, and identification of RAS mutation status. Identification of CMS 1 or 4 and MSS by screening tests. 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 \[Additional cohort to the Phase II part\] In accordance with Cohort B in the Phase II part. 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 and the additional cohort to the Phase II part) 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 1 year | Objective response rate determined by RECIST version 1.1: for additional cohort to the Phase II part |
| irORR | 2 years | Immune-related objective response rate determined by their Response Evaluation Criteria In Solid Tumors (RESIST): for the Phase II part |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 2 years | Objective response rate determined by RECIST version 1.1: for the Phase II part |
| irORR | 1 year | Immune-related objective response rate determined by their Response Evaluation Criteria In Solid Tumors (RESIST): for additional cohort to the Phase II part |
| Progression free survival rate at week 12 determined by the RECIST version 1.1 | 12 weeks | PFS |
| OS | 4 years | Overall survival |
| DCR | 2 years | Disease Control rate |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 4 years | Incidence of adverse events |
| Pharmacokinetic | 2 months | Area under the blood concentration-time curve (AUC) |
| PFS | 3 years | Progression free survival |
| irPFS | 12 weeks | Immune-related progression free survival rate at week 12 determined by the irRECIST |
Other
| Measure | Time frame | Description |
|---|---|---|
| efficacy according to immune status - Immune status will be analyzed using biopsy and blood samples by flow cytometry, RNA seq, whole exome sequencing, and immunohistochemistry etc. | 3 years | Efficacy evaluations according to immune status |
| safety according to immune status | 3 years | Safety evaluations according to immune status |
Countries
Japan
Outcome results
None listed