metastatic colorectal cancer
Conditions
Interventions
1 cycle is 21days. BBI608: Oral administration at a dose of 240mg or 480 mg BID, every day Pembrolizumab: Administration at a dose of 200 mg/body on Day 1 of each cycle The therapy will be repeated
Sponsors
National Cancer Center Hospital East
Eligibility
Sex/Gender
All
Inclusion criteria
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. 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 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. 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
Exclusion criteria
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 ECG abnormalities 16. Patients with a history of HIV 17. Patients with active hepatitis B or C
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Immune-related objective response rate (irORR) determined by their Response Evaluation Criteria In Solid Tumors (irRECIST) [Additional cohort to the Phase II part] Objective response rate determined by the RECIST version 1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Immune-related progression free survival (irPFS) rate at Week 12 determined by the irRECIST Objective response rate determined by the RECIST version 1.1 Progression free survival rate at Week 12 determined by the RECIST version 1.1 PFS Overall survival Disease control rate Incidence of adverse events Pharmacokinetic parameters [Additional cohort to the Phase II part] Immune-related objective response rate by irRECIST Progression free survival, Overall Survival, Disease Control Rate The incidence of adverse events | — |
Countries
Japan
Contacts
Public ContactYasutoshi Kuboki, Akihito Kawazoe
National Cancer Center Hospital East Department of Experimental Therapeutics and GI Oncology
Outcome results
None listed