Special Combination of BBI608 and Pembrolizumab

NCT02851004 | Terminated Phase 1 DMC

• 1 other identifier: EPOC1503
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

the efficacy and safety of BBI608 in combination with pembrolizumab

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• irORR

  Immune-related objective response rate determined by their Response Evaluation Criteria In Solid Tumors (RESIST): for the Phase II part

  2 years

• ORR

  Objective response rate determined by RECIST version 1.1: for additional cohort to the Phase II part

  1 year

Secondary Outcomes (10)

• irPFS

  12 weeks

• ORR

  2 years

• irORR

  1 year

• Progression free survival rate at week 12 determined by the RECIST version 1.1

  12 weeks

• PFS

  3 years

Other Outcomes (2)

• 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

• safety according to immune status

  3 years

Study Arms (1)

BBI608 + Pembrolizumab

EXPERIMENTAL

BBI608 and Pembrolizumab

Drug: Napabucasin; Drug: Pembrolizumab

Interventions

Napabucasin DRUG

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.

BBI608 + Pembrolizumab

Pembrolizumab DRUG

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.

BBI608 + Pembrolizumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Patients who personally provided written consent to be the subjects of the study
• Age of 20 years or older on the day of informed consent
• \[Phase Ib\] 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.
• \[Phase Ib\] 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.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1
• 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
• Patients with adequate organ function based on the following laboratory values measured within 7 days before enrollment
• 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
• Patients with an expected survival of at least 3 months
• 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
• 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

Sponsors & Collaborators

• Takayuki Yoshino: lead
• Sumitomo Pharma Co., Ltd.: collaborator

Study Sites (1)

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

napabucasin; pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Takayuki Yoshino, Dr

  National Cancer Center Hospital East

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Gastrointestinal Oncology Division

Model Details: \[Phase Ib\] 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.

Study Record Dates

• First Submitted: July 14, 2016
• First Posted: August 1, 2016
• Study Start: October 1, 2016
• Primary Completion: February 3, 2020
• Study Completion: August 23, 2021
• Last Updated: September 5, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)