Trial Outcomes & Findings for A Study of Napabucasin (BBI-608) in Combination With FOLFIRI in Adult Patients With Previously Treated Metastatic Colorectal Cancer (NCT NCT02753127)

Last Updated: 2023-11-15

Results Overview

Overall survival was defined as the time from randomization until death from any cause. Patients who are alive at the time of the interim or the final analyses or who have become lost to follow-up will be censored on the date the patient was last known to be alive.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1253 participants

Primary outcome timeframe

Randomization to Date of Death from any cause or database cutoff date (28 Apr 2020) (Approximately 43 months)

Results posted on

2023-11-15

Participant Flow

1253 participants were randomized between October 2016 and March 2019.

Completers included patients who died, withdrew consent to survival follow up or were lost to follow up.

Participant milestones

Participant milestones
Measure	Napabucasin + FOLFIRI ± Bevacizumab Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose). Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle	FOLFIRI ± Bevacizumab Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle.
Overall Study STARTED	624	629
Overall Study Discontinued Due to Death	507	499
Overall Study Completion of Survival Follow-Up Due to Study Completion	64	62
Overall Study COMPLETED	571	561
Overall Study NOT COMPLETED	53	68

Reasons for withdrawal

Reasons for withdrawal
Measure	Napabucasin + FOLFIRI ± Bevacizumab Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose). Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle	FOLFIRI ± Bevacizumab Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle.
Overall Study Lost to Follow-up	13	11
Overall Study Withdrawal by Subject	37	47
Overall Study Other	3	8
Overall Study Hospice	0	2

Baseline Characteristics

A Study of Napabucasin (BBI-608) in Combination With FOLFIRI in Adult Patients With Previously Treated Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Napabucasin + FOLFIRI ± Bevacizumab n=624 Participants Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose). Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle.	FOLFIRI ± Bevacizumab n=629 Participants Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle	Total n=1253 Participants Total of all reporting groups
Age, Continuous	60.1 years STANDARD_DEVIATION 11.17 • n=5 Participants	59.6 years STANDARD_DEVIATION 11.14 • n=7 Participants	59.8 years STANDARD_DEVIATION 11.16 • n=5 Participants
Sex: Female, Male Female	240 Participants n=5 Participants	254 Participants n=7 Participants	494 Participants n=5 Participants
Sex: Female, Male Male	384 Participants n=5 Participants	375 Participants n=7 Participants	759 Participants n=5 Participants
Race/Ethnicity, Customized White	375 participants n=5 Participants	370 participants n=7 Participants	745 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	29 participants n=5 Participants	38 participants n=7 Participants	67 participants n=5 Participants
Race/Ethnicity, Customized Asian	197 participants n=5 Participants	194 participants n=7 Participants	391 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	9 participants n=5 Participants	12 participants n=7 Participants	21 participants n=5 Participants
Race/Ethnicity, Customized Missing	13 participants n=5 Participants	14 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment Singapore	8 participants n=5 Participants	9 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment Hong Kong	1 participants n=5 Participants	11 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment United States	203 participants n=5 Participants	209 participants n=7 Participants	412 participants n=5 Participants
Region of Enrollment Czechia	18 participants n=5 Participants	19 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment Japan	63 participants n=5 Participants	63 participants n=7 Participants	126 participants n=5 Participants
Region of Enrollment Spain	74 participants n=5 Participants	62 participants n=7 Participants	136 participants n=5 Participants
Region of Enrollment Canada	21 participants n=5 Participants	15 participants n=7 Participants	36 participants n=5 Participants
Region of Enrollment Netherlands	16 participants n=5 Participants	21 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment South Korea	44 participants n=5 Participants	39 participants n=7 Participants	83 participants n=5 Participants
Region of Enrollment Belgium	16 participants n=5 Participants	24 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment China	62 participants n=5 Participants	59 participants n=7 Participants	121 participants n=5 Participants
Region of Enrollment Italy	22 participants n=5 Participants	29 participants n=7 Participants	51 participants n=5 Participants
Region of Enrollment Israel	8 participants n=5 Participants	10 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Australia	36 participants n=5 Participants	24 participants n=7 Participants	60 participants n=5 Participants
Region of Enrollment France	20 participants n=5 Participants	21 participants n=7 Participants	41 participants n=5 Participants
Region of Enrollment Germany	12 participants n=5 Participants	14 participants n=7 Participants	26 participants n=5 Participants
ECOG Performance Status ECOG: 0	333 Participants n=5 Participants	332 Participants n=7 Participants	665 Participants n=5 Participants
ECOG Performance Status ECOG: 1	291 Participants n=5 Participants	297 Participants n=7 Participants	588 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to Date of Death from any cause or database cutoff date (28 Apr 2020) (Approximately 43 months)

Population: The pSTAT3 subpopulations will be defined by the results of a Clinical Trial Assay (CTA) for a specimen with an age within a defined cut-section stability (CSS) window. A patient with positive pSTAT3 status within a defined CSS window is the one with pSTAT3 positive designated by CTA with specimen age up to 6 months at interim analysis or up to the final CSS window at final analysis.

Outcome measures

Outcome measures
Measure	Napabucasin + FOLFIRI ± Bevacizumab n=624 Participants Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose). Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle.	FOLFIRI ± Bevacizumab n=629 Participants Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle
Overall Survival (OS) Overall Survival (OS), General Population(GP)	14.29 months Interval 13.34 to 15.7	13.83 months Interval 12.42 to 15.28
Overall Survival (OS) Overall Survival (OS), ITT-pSTAT3(+)	13.17 months Interval 11.3 to 15.31	12.12 months Interval 11.24 to 14.06

SECONDARY outcome

Timeframe: Randomization to Date of Death or until the date of first documented objective disease progression or database cutoff date (28 Apr 2020) (Approximately 43 months)

PFS is defined as the time from randomization to the first objective documentation of disease progression per RECIST 1.1 (PD) or death, whichever comes first.

Outcome measures

Outcome measures
Measure	Napabucasin + FOLFIRI ± Bevacizumab n=624 Participants Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose). Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle.	FOLFIRI ± Bevacizumab n=629 Participants Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle
Progression-Free Survival (PFS) Progression-Free Survival (PFS), General Population(GP)	5.55 months Interval 5.39 to 5.78	5.62 months Interval 5.45 to 6.34
Progression-Free Survival (PFS) Progression-Free Survival (PFS) , ITT-pSTAT3(+)	5.39 months Interval 4.14 to 5.62	5.55 months Interval 4.44 to 5.91

SECONDARY outcome

Timeframe: Randomization to Date of Death or until the date of first documented objective disease progression or database cutoff date (28 Apr 2020) (Approximately 43 months)

Population: Analysis population of DCR will be based on patients with measurable disease by RECIST 1.1 at randomization. A patient with positive pSTAT3 status within a defined CSS window is the one with pSTAT3 positive designated by CTA with specimen age up to 6 months at interim analysis or up to the final CSS window at final analysis.

DCR is defined as the percentage of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1. The primary estimate of DCR will be based on patients with measurable disease by RECIST 1.1 at randomization

Outcome measures

Outcome measures
Measure	Napabucasin + FOLFIRI ± Bevacizumab n=593 Participants Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose). Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle.	FOLFIRI ± Bevacizumab n=609 Participants Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle
Disease Control Rate (DCR) Disease Control Rate (DCR), General Population(GP)	69.6 percentage of participants Interval 65.8 to 73.3	69.1 percentage of participants Interval 65.3 to 72.8
Disease Control Rate (DCR) Disease Control Rate (DCR), ITT-pSTAT3(+)	67.2 percentage of participants Interval 61.2 to 72.8	70.3 percentage of participants Interval 64.4 to 75.7

SECONDARY outcome

Timeframe: Randomization to Date of Death or until the date of first documented objective disease progression or database cutoff date (28 Apr 2020) (Approximately 43 months)

Population: Analysis set for ORR will be based on patients with measurable disease by RECIST 1.1 at randomization.

ORR is defined as the proportion of patients with a documented complete response and partial response (CR + PR) based on RECIST 1.1. The primary estimate for ORR will be based on patients with measurable disease by RECIST 1.1 at randomization.

Outcome measures

Outcome measures
Measure	Napabucasin + FOLFIRI ± Bevacizumab n=593 Participants Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose). Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle.	FOLFIRI ± Bevacizumab n=609 Participants Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle
Objective Response Rate (ORR) Objective Response Rate (ORR), General Population(GP)	13.8 percentage of participants Interval 11.2 to 16.9	14.6 percentage of participants Interval 11.9 to 17.7
Objective Response Rate (ORR) Objective Response Rate (ORR), ITT-pSTAT3(+)	11.9 percentage of participants Interval 8.3 to 16.4	13.9 percentage of participants Interval 10.0 to 18.7

SECONDARY outcome

Timeframe: From baseline at Time 2 (Cycle 5 Day 1), approximately 57 days and Time 4 (Cycle 9 Day 1), approximately 113 days

Population: The number of patients is with at least one valid assessment at each analysis window

The Quality of Life (QoL) of patients will be assessed using European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC-QLQ-C30) (EORTC QLQ-30) while the patient remains on study treatment (FOLFIRI with or without BBI-608). EORTC QLQ-30 is used to assess the overall quality of life in cancer patients using 28 questions with a 4 point scale. (1 'Not at all' to 4'Very Much'); 2 questions use a 7-point sale (1 'Very Poor' to 7 'Excellent'). Scores are averaged and transformed to 0-100 scale; higher overall score = better quality of life.

Outcome measures

Outcome measures
Measure	Napabucasin + FOLFIRI ± Bevacizumab n=622 Participants Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose). Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle.	FOLFIRI ± Bevacizumab n=626 Participants Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle
Mean Change From Baseline for Global Health Status at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1). Mean Change From Baseline for Global Health status at Time 2 (Cycle 5 Day 1). General Population	-7.07 score on a scale Standard Deviation 21.936	-5.45 score on a scale Standard Deviation 20.607
Mean Change From Baseline for Global Health Status at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1). Mean Change From Baseline for Global Health status at Time 4 (Cycle 9 Day 1). General Population	-7.70 score on a scale Standard Deviation 21.932	-5.58 score on a scale Standard Deviation 21.590

SECONDARY outcome

Timeframe: From baseline at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1)

Population: The number of patients is with at least one valid assessment at each analysis window.

Outcome measures

Outcome measures
Measure	Napabucasin + FOLFIRI ± Bevacizumab n=622 Participants Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose). Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle.	FOLFIRI ± Bevacizumab n=626 Participants Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle
Mean Change From Baseline for Physical Functioning Status at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1). Mean Change From Baseline for Physical Functioning at Time 2 (Cycle 5 Day 1). General Population	-5.86 QOL score on a scale Standard Deviation 17.204	-3.94 QOL score on a scale Standard Deviation 14.472
Mean Change From Baseline for Physical Functioning Status at Time 2 (Cycle 5 Day 1) and Time 4 (Cycle 9 Day 1). Mean Change From Baseline for Physical Functioning at Time 4 (Cycle 9 Day 1). General Population	-6.37 QOL score on a scale Standard Deviation 15.095	-4.22 QOL score on a scale Standard Deviation 15.023

SECONDARY outcome

Timeframe: All adverse event are collected from date of signed informed consent until 30 days after protocol treatment discontinuation. Outcome followed until study discontinuation up to 4 years

Population: All patients who received at least 1 dose of study drug (BBI-608 and/or FOLFIRI) with treatment assignment designated according to the actual study treatment received. Adverse event is analyzed in the SAS population.

All patients who have received at least one dose of either BBI-608 or FOLFIRI will be included in the safety analysis according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.0. The incidence of adverse events will be summarized by type of adverse event and severity.

Outcome measures

Outcome measures
Measure	Napabucasin + FOLFIRI ± Bevacizumab n=622 Participants Napabucasin 240 mg will be administered orally, twice daily, with doses separated by approximately 12 hours (480 mg total daily dose). Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will start at least 2 hours following the first daily dose of napabucasin and will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion or at least 2 hours following the first daily dose of napabucasin if bevacizumab is not administered. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle.	FOLFIRI ± Bevacizumab n=610 Participants Addition of bevacizumab to the FOLFIRI regimen will be permissible. FOLFIRI chemotherapy infusion will be administered every 2 weeks. Irinotecan/leucovorin infusion will follow bevacizumab infusion in selected patients to receive standard dose of bevacizumab (5 mg/kg). Irinotecan 180 mg/m\^2 together with leucovorin 400 mg/m\^2 will be administered intravenously, over approximately 90 minutes and 2 hours, respectively, starting on Day 1 of Cycle 1, following bevacizumab infusion. 5-FU 400 mg/m\^2 bolus will be administered intravenously immediately following irinotecan/leucovorin infusion, followed by 5-FU 1200 mg/m\^2/day (total 2400 mg/m\^2) continuous infusion. This regimen will be repeated on Day 1 of every 14 day cycle
Number of Patients With Adverse Events in the General Population Number of Patients with Adverse Events in the General Population	619 Participants	602 Participants
Number of Patients With Adverse Events in the General Population Number of Patients with Adverse Events in the pSTAT3(+) Subpopulation	275 Participants	266 Participants

Adverse Events

Napabucasin + FOLFIRI ± Bevacizumab

Serious events: 234 serious events

Other events: 619 other events

Deaths: 507 deaths

FOLFIRI ± Bevacizumab

Serious events: 201 serious events

Other events: 602 other events

Deaths: 499 deaths

Serious adverse events

Other adverse events

Additional Information

Keiichi Saito

Sumitomo Dainippon Pharma Oncology

Phone: +1 (617)674-6800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place