Trial Outcomes & Findings for A Study of BBI608 in Adult Patients With Advanced Colorectal Cancer (NCT NCT01776307)

NCT ID: NCT01776307

Last Updated: 2023-11-15

Results Overview

Assessment of Disease Control Rate, defined as the proportion of patients with a documented complete response, partial response and stable disease based on RECIST 1.1, in patients with advanced colorectal cancer given napabucasin in combination with cetuximab, panitumumab or capecitabine

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 200 participants
• Primary outcome timeframe: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months
• Results posted on: 2023-11-15

Participant Flow

200 participants were enrolled between March 2012 and July 2017.

Patients who died, withdrew consent to survival follow up or were lost to follow up were considered to have completed the study.

Participant milestones

Measure	Napabucasin Plus Cetuximab All participants who were enrolled to Arm A to receive napabucasin administered orally, twice daily in combination with weekly cetuximab administered intravenously	Napabucasin Plus Panitumumab All participants who were enrolled to Arm B to receive napabucasin administered orally, twice daily in combination with panitumumab administered intravenously on day 8 and 22 of each 28 day cycle	Napabucasin Plus Capecitabine All participants who were enrolled to Arm C to receive napabucasin administered orally, twice daily in combination with capecitabine administered twice daily on days 8-21 every three weeks
Overall Study STARTED	49	75	76
Overall Study COMPLETED	49	75	75
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Measure	Napabucasin Plus Cetuximab All participants who were enrolled to Arm A to receive napabucasin administered orally, twice daily in combination with weekly cetuximab administered intravenously	Napabucasin Plus Panitumumab All participants who were enrolled to Arm B to receive napabucasin administered orally, twice daily in combination with panitumumab administered intravenously on day 8 and 22 of each 28 day cycle	Napabucasin Plus Capecitabine All participants who were enrolled to Arm C to receive napabucasin administered orally, twice daily in combination with capecitabine administered twice daily on days 8-21 every three weeks
Overall Study Not dosed	0	0	1

Baseline Characteristics

A Study of BBI608 in Adult Patients With Advanced Colorectal Cancer

Baseline characteristics by cohort

Measure	Napabucasin Plus Cetuximab n=49 Participants All participants who were enrolled to Arm A to receive napabucasin administered orally, twice daily in combination with weekly cetuximab administered intravenously	Napabucasin Plus Panitumumab n=75 Participants All participants who were enrolled to Arm B to receive napabucasin administered orally, twice daily in combination with panitumumab administered intravenously on day 8 and 22 of each 28 day cycle	Napabucasin Plus Capecitabine n=75 Participants All participants who were enrolled to Arm C to receive napabucasin administered orally, twice daily in combination with capecitabine administered twice daily on days 8-21 every three weeks	Total n=199 Participants Total of all reporting groups
Age, Customized	56.3 years STANDARD_DEVIATION 10.37 • n=5 Participants	59.7 years STANDARD_DEVIATION 11.94 • n=7 Participants	58.1 years STANDARD_DEVIATION 11.20 • n=5 Participants	58.3 years STANDARD_DEVIATION 11.31 • n=4 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	35 Participants n=7 Participants	24 Participants n=5 Participants	86 Participants n=4 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	40 Participants n=7 Participants	51 Participants n=5 Participants	113 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	14 Participants n=4 Participants
Race (NIH/OMB) White	39 Participants n=5 Participants	69 Participants n=7 Participants	64 Participants n=5 Participants	172 Participants n=4 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months

Population: Patients who received at least 1 cycle of study treatment and had at least 1 disease assessment following the initiation of therapy. Patients missing imaging assessment following the initiation of treatment are not included in the assessment for DCR.

Assessment of Disease Control Rate, defined as the proportion of patients with a documented complete response, partial response and stable disease based on RECIST 1.1, in patients with advanced colorectal cancer given napabucasin in combination with cetuximab, panitumumab or capecitabine

Outcome measures

Measure	Napabucasin Plus Cetuximab n=29 Participants Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab n=41 Participants Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine n=39 Participants Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Disease Control Rate	34.5 Percentage of participants Interval 17.9 to 54.3	36.6 Percentage of participants Interval 22.1 to 53.1	25.6 Percentage of participants Interval 13.0 to 42.1

SECONDARY outcome

Timeframe: The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause, up to 24 months

The effect of napabucasin given in combination with cetuximab, panitumumab or capecitabine on Progression Free Survival (PFS) of patients with advanced colorectal cancer.

Outcome measures

Measure	Napabucasin Plus Cetuximab n=49 Participants Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab n=75 Participants Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine n=75 Participants Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Progression Free Survival	1.87 months Interval 1.81 to 3.65	2.27 months Interval 2.04 to 3.58	1.94 months Interval 1.71 to 2.73

SECONDARY outcome

Timeframe: 4 weeks after the patient has been off study treatment, every 3 months thereafter until death, up to 60 months.

The effect of napabucasin given in combination with cetuximab, panitumumab or capecitabine on the Overall Survival of patients with advanced colorectal cancer

Outcome measures

Measure	Napabucasin Plus Cetuximab n=49 Participants Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab n=75 Participants Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine n=75 Participants Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Overall Survival	7.79 Months Interval 5.49 to 8.54	9.10 Months Interval 5.88 to 12.48	6.34 Months Interval 5.13 to 11.33

SECONDARY outcome

Timeframe: Blood samples drawn on day 5 during the first study cycle

Population: Napabucasin plus capecitabine: No evaluable patients dosed at 480mg twice daily.

To determine the maximum concentration of napabucasin when given at 480mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.

Outcome measures

Measure	Napabucasin Plus Cetuximab n=6 Participants Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab n=1 Participants Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 480mg, Twice Daily, on Day 5 of the First Study Cycle	661 ng/mL Geometric Coefficient of Variation 77.9	468 ng/mL Geometric Coefficient of Variation NA Not calculated	—

SECONDARY outcome

Timeframe: Blood samples drawn on day 21 during the first study cycle

Population: Napabucasin plus capecitabine: No evaluable patients dosed at 480mg twice daily.

To determine the maximum concentration of napabucasin when given at 480mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.

Outcome measures

Measure	Napabucasin Plus Cetuximab n=5 Participants Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab n=1 Participants Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 480mg, Twice Daily, on Day 21 of the First Study Cycle	627 ng/mL Geometric Coefficient of Variation 77.3	398 ng/mL Geometric Coefficient of Variation NA Not calculated	—

SECONDARY outcome

Timeframe: Blood samples drawn on day 21 during the first study cycle

Population: Napabucasin plus panitumumab \& Napabucasin plus capecitabine: No evaluable patients dosed at 240mg twice daily.

To determine the maximum concentration of napabucasin when given at 240mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.

Outcome measures

Measure	Napabucasin Plus Cetuximab n=1 Participants Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 240mg, Twice Daily, on Day 21 of the First Study Cycle	494 ng/mL Geometric Coefficient of Variation NA Not calculated	—	—

SECONDARY outcome

Timeframe: Blood samples drawn on day 5 during the first study cycle

Population: Napabucasin plus cetuximab: No evaluable patients dosed at 500mg twice daily.

To determine the maximum concentration of napabucasin when given at 500mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.

Outcome measures

Measure	Napabucasin Plus Cetuximab Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab n=4 Participants Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine n=6 Participants Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 500mg, Twice Daily, on Day 5 of the First Study Cycle	—	1020 ng/mL Geometric Coefficient of Variation 50.6	858 ng/mL Geometric Coefficient of Variation 34.5

SECONDARY outcome

Timeframe: Blood samples drawn on day 21 during the first study cycle

Population: Napabucasin plus cetuximab: No evaluable patients dosed at 500mg twice daily.

To determine the maximum concentration of napabucasin when given at 500mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.

Outcome measures

Measure	Napabucasin Plus Cetuximab Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab n=3 Participants Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine n=5 Participants Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 500mg, Twice Daily, on Day 21 of the First Study Cycle	—	1060 ng/mL Geometric Coefficient of Variation 23.0	789 ng/mL Geometric Coefficient of Variation 72.0

SECONDARY outcome

Timeframe: Blood samples drawn on day 5 during the first study cycle

Population: Napabucasin plus capecitabine: No evaluable patients dosed at 480mg twice daily.

To determine the area under the plasma concentration vs. time curve of napabucasin when given at 480mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.

Outcome measures

Measure	Napabucasin Plus Cetuximab n=6 Participants Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab n=1 Participants Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 480mg, Twice Daily, on Day 5 of the First Study Cycle	3380 h*ng/mL Geometric Coefficient of Variation 83.3	2730 h*ng/mL Geometric Coefficient of Variation NA Not calculated	—

SECONDARY outcome

Timeframe: Blood samples drawn on day 21 during the first study cycle

Population: Napabucasin plus capecitabine: No evaluable patients dosed at 480mg twice daily.

To determine the area under the plasma concentration vs. time curve of napabucasin when given at 480mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.

Outcome measures

Measure	Napabucasin Plus Cetuximab n=5 Participants Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab n=1 Participants Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 480mg, Twice Daily, on Day 21 of the First Study Cycle	2930 h*ng/mL Geometric Coefficient of Variation 137	2630 h*ng/mL Geometric Coefficient of Variation NA Not calculated	—

SECONDARY outcome

Timeframe: Blood samples drawn on day 21 during the first study cycle

Population: Napabucasin plus panitumumab and Napabucasin plus capecitabine: No evaluable patients dosed at 240mg twice daily.

To determine the area under the plasma concentration vs. time curve of napabucasin when given at 240mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.

Outcome measures

Measure	Napabucasin Plus Cetuximab n=1 Participants Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 240mg, Twice Daily, on Day 21 of the First Study Cycle	2870 h*ng/mL Geometric Coefficient of Variation NA Not calculated	—	—

SECONDARY outcome

Timeframe: Blood samples drawn on day 5 during the first study cycle

Population: Napabucasin plus cetuximab: No evaluable patients dosed at 500mg twice daily.

To determine the area under the plasma concentration vs. time curve of napabucasin when given at 500mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.

Outcome measures

Measure	Napabucasin Plus Cetuximab Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab n=4 Participants Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine n=6 Participants Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 500mg, Twice Daily, on Day 5 of the First Study Cycle	—	5420 h*ng/mL Geometric Coefficient of Variation 36.3	5350 h*ng/mL Geometric Coefficient of Variation 38.7

SECONDARY outcome

Timeframe: Blood samples drawn on day 21 during the first study cycle

Population: Napabucasin plus cetuximab: No evaluable patients dosed at 500mg twice daily.

To determine the area under the plasma concentration vs. time curve of napabucasin when given at 500mg, twice daily, in combination with cetuximab, panitumumab, or capecitabine in patients with advanced colorectal cancer.

Outcome measures

Measure	Napabucasin Plus Cetuximab Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab n=3 Participants Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine n=5 Participants Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 500mg, Twice Daily, on Day 21 of the First Study Cycle	—	6290 h*ng/mL Geometric Coefficient of Variation 6.71	4720 h*ng/mL Geometric Coefficient of Variation 48.2

SECONDARY outcome

Timeframe: During the first 28 days of the study cycle

Population: No on-treatment biopsies were performed therefore no pharmacodynamic testing on tumor tissue was conducted.

To determine the response (increase or decrease) of biomarkers from biopsied tumors following the administration of napabucasin

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: The time from the date of first treatment, while the patient is taking napabucasin, and for 30 days after stopping therapy, an average of 4 months.

Assessment of safety of napabucasin given in combination with cetuximab, panitumumab or capecitabine to patients with advanced colorectal cancer by reporting of adverse events and serious adverse events

Outcome measures

Measure	Napabucasin Plus Cetuximab n=49 Participants Napabucasin administered orally, twice daily, in combination with weekly cetuximab administered intravenously on Days 5, 12, 19, and 26 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Panitumumab n=75 Participants Napabucasin administered orally, twice daily, in combination with panitumumab administered intravenously on Days 8 and 22 of each 28 day study cycle. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.	Napabucasin Plus Capecitabine n=75 Participants Napabucasin administered orally, twice daily, in combination with capecitabine administered twice daily on Days 8-21 every three weeks. Patients in this group had a baseline scan and at least one assessment approximately 8 weeks from baseline.
Number of Patients With Adverse Events and Serious Adverse Events	49 Participants	75 Participants	75 Participants

Adverse Events

Napabucasin Plus Cetuximab

Serious events: 17 serious events

Other events: 49 other events

Deaths: 45 deaths

Napabucasin Plus Panitumumab

Serious events: 29 serious events

Other events: 75 other events

Deaths: 70 deaths

Napabucasin Plus Capecitabine

Serious events: 26 serious events

Other events: 75 other events

Deaths: 72 deaths

Serious adverse events

Measure	Napabucasin Plus Cetuximab n=49 participants at risk All participants who received at least 1 dose of napabucasin administered orally, twice daily in combination with weekly cetuximab administered intravenously	Napabucasin Plus Panitumumab n=75 participants at risk All participants who received at least 1 dose of napabucasin administered orally, twice daily in combination with panitumumab administered intravenously on day 8 and 22 of each 28 day cycle	Napabucasin Plus Capecitabine n=75 participants at risk All participants who received at least 1 dose of napabucasin administered orally, twice daily in combination with capecitabine administered twice daily on days 8-21 every three weeks
Gastrointestinal disorders Abdominal pain	8.2% 4/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	5.3% 4/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Diarrhoea	8.2% 4/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Nausea	4.1% 2/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Constipation	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Gastrointestinal haemorrhage	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Large intestine perforation	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Small intestinal obstruction	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Vomiting	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Ascites	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Colitis	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.1% 2/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Disease progression	6.1% 3/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Pyrexia	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Chest pain	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Device dislocation	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Oedema peripheral	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Asthenia	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Pain	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Hepatobiliary disorders Bile duct obstruction	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Hepatobiliary disorders Hepatic failure	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Hepatobiliary disorders Cholangitis	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Immune system disorders Anaphylactic reaction	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Infections and infestations Sepsis	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Infections and infestations Clostridium difficile infection	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Infections and infestations Urinary tract infection	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Infections and infestations Pneumonia	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Dehydration	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Renal and urinary disorders Acute kidney injury	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Renal and urinary disorders Haematuria	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Cardiac disorders Atrial fibrillation	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Cardiac disorders Pericardial effusion	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Investigations Blood bilirubin increased	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Investigations Blood creatinine increased	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Skin and subcutaneous tissue disorders Rash	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Skin and subcutaneous tissue disorders Skin disorder	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Blood and lymphatic system disorders Anaemia	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Injury, poisoning and procedural complications Renal haematoma	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Nervous system disorders Haemorrhage intracranial	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Nervous system disorders Hemiparesis	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Nervous system disorders Hepatic encephalopathy	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Vascular disorders Hypotension	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Vascular disorders Thrombosis	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.

Other adverse events

Measure	Napabucasin Plus Cetuximab n=49 participants at risk All participants who received at least 1 dose of napabucasin administered orally, twice daily in combination with weekly cetuximab administered intravenously	Napabucasin Plus Panitumumab n=75 participants at risk All participants who received at least 1 dose of napabucasin administered orally, twice daily in combination with panitumumab administered intravenously on day 8 and 22 of each 28 day cycle	Napabucasin Plus Capecitabine n=75 participants at risk All participants who received at least 1 dose of napabucasin administered orally, twice daily in combination with capecitabine administered twice daily on days 8-21 every three weeks
Gastrointestinal disorders Diarrhoea	75.5% 37/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	77.3% 58/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	81.3% 61/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Abdominal pain	51.0% 25/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	34.7% 26/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	40.0% 30/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Nausea	44.9% 22/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	52.0% 39/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	62.7% 47/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Vomiting	44.9% 22/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	36.0% 27/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	36.0% 27/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Constipation	30.6% 15/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	12.0% 9/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	13.3% 10/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Abdominal pain upper	12.2% 6/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	8.0% 6/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	9.3% 7/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Ascites	4.1% 2/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Abdominal distension	6.1% 3/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	8.0% 6/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Gastrointestinal disorders Stomatitis	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	5.3% 4/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Decreased appetite	30.6% 15/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	32.0% 24/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	30.7% 23/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Hypomagnesaemia	30.6% 15/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	30.7% 23/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	5.3% 4/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Hypokalaemia	24.5% 12/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	30.7% 23/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	20.0% 15/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Hypoalbuminaemia	16.3% 8/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	10.7% 8/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	24.0% 18/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Hypophosphataemia	14.3% 7/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Dehydration	12.2% 6/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	9.3% 7/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	13.3% 10/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Hyponatraemia	10.2% 5/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	16.0% 12/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Hyperglycaemia	8.2% 4/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	20.0% 15/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	29.3% 22/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Hypocalcaemia	4.1% 2/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Metabolism and nutrition disorders Hypouricaemia	20.4% 10/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	5.3% 4/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Skin and subcutaneous tissue disorders Dermatitis acneiform	20.4% 10/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	17.3% 13/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Skin and subcutaneous tissue disorders Dry skin	20.4% 10/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	8.0% 6/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Skin and subcutaneous tissue disorders Rash	18.4% 9/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	28.0% 21/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	12.2% 6/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	12.0% 9/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaethesia syndrome	4.1% 2/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	14.7% 11/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Fatigue	40.8% 20/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	57.3% 43/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	48.0% 36/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Oedema peripheral	12.2% 6/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	8.0% 6/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	10.7% 8/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Pyrexia	12.2% 6/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	9.3% 7/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Mucosal inflammation	10.2% 5/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Chills	6.1% 3/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	8.0% 6/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Disease progression	6.1% 3/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
General disorders Asthenia	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	9.3% 7/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Nervous system disorders Dizziness	14.3% 7/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	9.3% 7/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	12.0% 9/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Nervous system disorders Headache	10.2% 5/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	8.0% 6/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Renal and urinary disorders Chromaturia	22.4% 11/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	16.0% 12/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	13.3% 10/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Renal and urinary disorders Proteinuria	10.2% 5/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	14.7% 11/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	24.0% 18/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Renal and urinary disorders Ketonuria	6.1% 3/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	14.7% 11/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	22.7% 17/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Renal and urinary disorders Haematuria	4.1% 2/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	12.0% 9/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	13.3% 10/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Renal and urinary disorders Glycosuria	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	8.0% 6/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Blood and lymphatic system disorders Anaemia	18.4% 9/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	21.3% 16/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	21.3% 16/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Blood and lymphatic system disorders Lymphopenia	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	12.0% 9/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	24.0% 18/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Blood and lymphatic system disorders Thrombocytopenia	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	8.0% 6/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Blood and lymphatic system disorders Leukopenia	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	5.3% 4/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Investigations Blood alkaline phosphatase increased	14.3% 7/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	12.0% 9/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	16.0% 12/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Investigations Aspartate aminotransferase increased	12.2% 6/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	8.0% 6/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	17.3% 13/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Investigations Blood bilirubin increased	8.2% 4/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	8.0% 6/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Investigations Alanine aminotransferase increased	8.2% 4/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Investigations Blood lactate dehydrogenase increased	8.2% 4/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Investigations Blood creatinine increased	6.1% 3/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Investigations Weight decreased	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Investigations Protein total decreased	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.3% 7/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	17.3% 13/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	17.3% 13/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Respiratory, thoracic and mediastinal disorders Cough	4.1% 2/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	12.0% 9/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	13.3% 10/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	4.1% 2/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	5.3% 4/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Infections and infestations Urinary tract infection	8.2% 4/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	20.0% 15/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	8.0% 6/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Musculoskeletal and connective tissue disorders Back pain	8.2% 4/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	8.0% 6/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Musculoskeletal and connective tissue disorders Muscle spasms	8.2% 4/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	5.3% 4/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.2% 4/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Musculoskeletal and connective tissue disorders Muscular weakness	6.1% 3/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Musculoskeletal and connective tissue disorders Pain in extremity	6.1% 3/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Musculoskeletal and connective tissue disorders Arthralgia	4.1% 2/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	2.7% 2/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	5.3% 4/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Eye disorders Vision blurred	8.2% 4/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Psychiatric disorders Insomnia	8.2% 4/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Psychiatric disorders Anxiety	6.1% 3/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Psychiatric disorders Depression	2.0% 1/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	6.7% 5/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	5.3% 4/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Vascular disorders Hypotension	6.1% 3/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	5.3% 4/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	4.0% 3/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Injury, poisoning and procedural complications Infusion related reaction	6.1% 3/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	0.00% 0/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.
Hepatobiliary disorders Hyperbilirubinaemia	4.1% 2/49 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	1.3% 1/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.	9.3% 7/75 • Serious and Other Adverse Events were assessed from the date of first treatment through 30 days of the last administration of study drug, an average of 4 months. All-Cause Mortality was assessed from the date of first treatment until death, assessed up to 60 months.

Additional Information

Tegan Nguyen

Sumitomo Dainippon Pharma Oncology

Phone: 617-674-8745

Email: tnguyen@bostonbiomedical.com

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor can review results communications prior to public release and embargo communications of results up to 60 days.
• Publication restrictions are in place

Restriction type: OTHER