Trial Outcomes & Findings for Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients (NCT NCT04737187)

NCT ID: NCT04737187

Last Updated: 2024-09-24

Results Overview

Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 492 participants
• Primary outcome timeframe: From date of randomization to the death due to any cause or cut-off date, whichever comes first (maximum duration: up to 20 months)
• Results posted on: 2024-09-24

Participant Flow

The study was conducted at 99 active sites in 13 countries. A total of 659 participants were screened, of which 492 participants were randomized and treated.

Randomization (1:1 ratio): stratified by geographic region (North America, European Union, Rest of the World), time since 1st metastasis diagnosis (less than [<] 18 months, greater than or equal to [>=] 18 months) and rat sarcoma virus status (wild-type, mutant). Primary analysis of overall survival as primary outcome measure was completed with cutoff date of July 19, 2022; no efficacy analysis was conducted after this cutoff and participants were continued to be followed for safety analysis.

Participant milestones

Measure	Trifluridine/Tipiracil + Bevacizumab Participants were administered 35 milligrams per square meter per dose (mg/m²/dose) trifluridine/tipiracil (FTD/TPI) orally twice a day (BID), within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab (5 milligrams per kilogram \[mg/kg\], intravenous \[IV\] infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Overall Study STARTED	246	246
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	246	246

Reasons for withdrawal

Measure	Trifluridine/Tipiracil + Bevacizumab Participants were administered 35 milligrams per square meter per dose (mg/m²/dose) trifluridine/tipiracil (FTD/TPI) orally twice a day (BID), within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab (5 milligrams per kilogram \[mg/kg\], intravenous \[IV\] infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Overall Study Switched to marketed drug	32	4
Overall Study Radiological Progressive Disease	145	146
Overall Study Clinical Progressive Disease	20	20
Overall Study Radiological And Clinical Progressive Disease	26	52
Overall Study Adverse Event	16	16
Overall Study Physician Decision	2	0
Overall Study Withdrawal by Subject	5	8

Baseline Characteristics

Phase III Study of Trifluridine/Tipiracil With and Without Bevacizumab in Refractory Metastatic Colorectal Cancer Patients

Baseline characteristics by cohort

Measure	Trifluridine/Tipiracil + Bevacizumab n=246 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=246 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.	Total n=492 Participants Total of all reporting groups
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	26 Participants n=93 Participants	22 Participants n=4 Participants	48 Participants n=27 Participants
Age, Continuous	62.00 years n=93 Participants	64.00 years n=4 Participants	63.00 years n=27 Participants
Age, Customized Adults (18-64 years)	146 Participants n=93 Participants	129 Participants n=4 Participants	275 Participants n=27 Participants
Age, Customized From 65-84 years	100 Participants n=93 Participants	116 Participants n=4 Participants	216 Participants n=27 Participants
Age, Customized 85 years and over	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Sex: Female, Male Female	124 Participants n=93 Participants	112 Participants n=4 Participants	236 Participants n=27 Participants
Sex: Female, Male Male	122 Participants n=93 Participants	134 Participants n=4 Participants	256 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	4 Participants n=93 Participants	3 Participants n=4 Participants	7 Participants n=27 Participants
Race (NIH/OMB) White	215 Participants n=93 Participants	220 Participants n=4 Participants	435 Participants n=27 Participants

PRIMARY outcome

Timeframe: From date of randomization to the death due to any cause or cut-off date, whichever comes first (maximum duration: up to 20 months)

Population: Analysis was performed on FAS population.

Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=246 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=246 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Overall Survival (OS)	10.78 months Interval 9.36 to 11.83	7.46 months Interval 6.34 to 8.57

PRIMARY outcome

Timeframe: From date of randomization until 6 months post treatment

Population: Analysis was performed on FAS population.

Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 6 months was reported.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=246 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=246 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Survival Probability at 6 Months	0.77 probability of participants Interval 0.72 to 0.82	0.61 probability of participants Interval 0.55 to 0.67

PRIMARY outcome

Timeframe: From date of randomization until 12 months post treatment

Population: Analysis was performed on FAS population.

Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 12 months was reported.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=246 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=246 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Survival Probability at 12 Months	0.43 probability of participants Interval 0.36 to 0.49	0.30 probability of participants Interval 0.24 to 0.36

PRIMARY outcome

Timeframe: From date of randomization until 18 months post treatment

Population: Analysis was performed on FAS population.

Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause. The primary estimand of interest was defined to assess the effect of the randomized treatments on the survival duration in all participants regardless of whether or not intercurrent events had occurred (treatment policy strategy). Analysis was performed using Kaplan- Meier method. In this outcome measure, data of survival probability at 18 months was reported.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=246 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=246 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Survival Probability at 18 Months	0.28 probability of participants Interval 0.19 to 0.37	0.15 probability of participants Interval 0.09 to 0.22

SECONDARY outcome

Timeframe: From randomization to the date of radiological tumour progression or death due to any cause or data cut-off date whichever comes first (i.e., up to 20 months)

Population: Analysis was performed on FAS population.

PFS was defined as the time elapsed between the date of randomisation and the date of radiological tumour progression as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by investigator, or death (from any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=246 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=246 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Progression Free Survival (PFS)	5.55 months Interval 4.5 to 5.88	2.40 months Interval 2.07 to 3.22

SECONDARY outcome

Timeframe: From randomization until 3, 6, 9, and 12 months post treatment

Population: Analysis was performed on FAS population.

PFS was defined as the time elapsed between the date of randomisation and the date of radiological tumour progression as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) assessed by investigator, or death (from any cause), whichever comes first. Progressive Disease (PD) as per RECIST 1.1: at least a 20 percent (%) increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions. Analysis was performed by Kaplan-Meier method. In this outcome measure, data of PFS at 3 months was reported.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=246 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=246 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Probability of Participants With Progression Free Survival at 3, 6, 9 and 12 Months At 3 Months	0.73 probability of participants Interval 0.67 to 0.78	0.45 probability of participants Interval 0.39 to 0.51
Probability of Participants With Progression Free Survival at 3, 6, 9 and 12 Months At 6 Months	0.43 probability of participants Interval 0.37 to 0.49	0.16 probability of participants Interval 0.11 to 0.21
Probability of Participants With Progression Free Survival at 3, 6, 9 and 12 Months At 9 Months	0.28 probability of participants Interval 0.22 to 0.34	0.05 probability of participants Interval 0.03 to 0.09
Probability of Participants With Progression Free Survival at 3, 6, 9 and 12 Months At 12 Months	0.16 probability of participants Interval 0.12 to 0.21	0.01 probability of participants Interval 0.0 to 0.03

SECONDARY outcome

Timeframe: From the date of randomization to the date of documentation of progression or death due to any cause or data cut-off, whichever occurred first (i.e., up to 20 months)

Population: Analysis was performed on FAS population.

Objective response was defined as percentage of participants who achieved complete response (CR) or partial response (PR) according to the RECIST version 1.1 and using investigator's tumour assessment. As per RECIST 1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=246 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=246 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Overall Response Rate (ORR)	6.10 percentage of participants Interval 3.45 to 9.86	1.22 percentage of participants Interval 0.25 to 3.52

SECONDARY outcome

Timeframe: From randomization to the date of first documented tumor progression, death due to any cause or data cut-off date whichever comes first (i.e., up to 20 months)

Population: Analysis was performed on FAS population.

Disease control is defined as percentage of participants who achieved CR or PR, or stable disease (SD) as per RECIST 1.1 and using investigator's tumour assessment from the date of randomization to until disease progression or death due to any cause. As per RECIST 1.1, CR: disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters. PD: at least 20% increase in sum of diameters of target lesions, unequivocal progression of existing non-target lesions.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=246 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=246 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Percentage of Participants With Disease Control	69.51 percentage of participants Interval 63.35 to 75.2	41.87 percentage of participants Interval 35.63 to 48.31

SECONDARY outcome

Timeframe: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months)

Population: Analysis was performed on safety set which included all participants who had taken at least one dose of investigational medicinal products and were analyzed according to the treatment they actually received.

An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TEAE period (time from the first dose of study treatment up to 30 days after the last dose of study treatment). TEAEs included both SAEs and non-SAEs.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=246 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=246 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs) TEAE	241 Participants	241 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAE) and Treatment-emergent Serious Adverse Events (TESAEs) TESAE	66 Participants	79 Participants

SECONDARY outcome

Timeframe: Date of randomization to first deterioration in QoL score >=10 points or death due to any cause, which ever occurred first (i.e., up to 20 months)

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

EORTC QLQ-C30: 30 item questionnaires with 5 multi-item functional subscales (physical, role, cognitive, emotional, social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), global health/quality of life (QOL) subscale and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4-point Likert scales with responses from "not at all" to "very much" and GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional & GHS/QoL = higher level of functioning, & higher score for symptoms scales = higher symptom burden. Time to definitive >=10 points deterioration: time from date of randomization to first deterioration in QoL score >=10 points compared to baseline with no later improvement or death due to any cause. Kaplan-Meier method was used.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=121 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=155 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Appetite loss	8.34 months Interval 6.7 to 10.94	4.66 months Interval 3.94 to 6.04
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Constipation	9.46 months Interval 8.34 to 12.12	5.55 months Interval 4.63 to 6.67
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Physical functioning	8.97 months Interval 8.15 to 11.83	4.50 months Interval 3.71 to 5.62
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Role functioning	8.57 months Interval 7.49 to 10.94	4.40 months Interval 3.78 to 5.06
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Emotional functioning	9.95 months Interval 8.51 to 12.12	5.85 months Interval 4.7 to 6.6
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Cognitive functioning	9.36 months Interval 8.34 to 12.25	4.73 months Interval 4.07 to 6.11
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Social functioning	8.97 months Interval 7.85 to 11.86	4.93 months Interval 4.14 to 5.88
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Fatigue	8.21 months Interval 6.11 to 9.95	4.04 months Interval 3.19 to 4.83
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Nausea and vomiting	9.36 months Interval 8.51 to 11.86	5.06 months Interval 4.27 to 6.31
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Pain	8.57 months Interval 6.96 to 10.41	4.34 months Interval 3.29 to 5.16
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Dyspnoea	9.36 months Interval 8.54 to 12.25	5.65 months Interval 4.4 to 6.6
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Insomnia	9.36 months Interval 8.54 to 12.25	5.75 months Interval 4.7 to 6.8
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Diarrhoea	10.41 months Interval 8.84 to 14.49	5.52 months Interval 4.7 to 6.6
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in Sub-scale Scores - Kaplan-Meier Analysis Financial difficulties	9.36 months Interval 8.34 to 12.12	6.11 months Interval 5.06 to 6.93

SECONDARY outcome

Timeframe: Date of randomization to first deterioration in QoL score >=10 points or death due to any cause, which ever occurred first (i.e., up to 20 months)

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

EORTC QLQ-C30: 30 item questionnaires composed of 5 multi-item functional subscales (physical, role, cognitive, emotional, social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), global health/QOL subscale and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4-point Likert scales with responses from "not at all" to "very much" and GHS/QoL, scored on scale of 1 (very poor) to 7 (excellent). All scales are transformed from raw scores to linear scales ranging 0 to 100. Higher score for functional & GHS/QoL = higher level of functioning, & higher score for symptoms scales = higher symptom burden. Time to definitive >=10 points deterioration: time from date of randomization to the first deterioration in QoL score >=10 points compared to baseline with no later improvement or death due to any cause. Kaplan-Meier method was used.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=120 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=141 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30): Time to Definitive Deterioration of >=10 Points in the Global Health Status Score - Kaplan-Meier Analysis	8.54 months Interval 7.49 to 10.94	4.70 months Interval 4.01 to 5.78

SECONDARY outcome

Timeframe: Baseline, Cycle 1, Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11, Cycle 12, Cycle 13 and Cycle 14

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

The EQ-5D-5L is a standardized measure of health status that provides a general assessment of health utility and consist in 2 sections a descriptive system comprising 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and Visual Analog Scale (VAS). Each dimension has a 5-level response: no problems, slight problems, moderate problems, severe problems, and extreme problems. Response options are measured with a 5-point Likert scale. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state and lower score indicate worse health state.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=201 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=207 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 6	-0.010 score on a scale Standard Deviation 0.112	-0.003 score on a scale Standard Deviation 0.094
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 5	-0.003 score on a scale Standard Deviation 0.101	0.004 score on a scale Standard Deviation 0.120
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 1	0.004 score on a scale Standard Deviation 0.125	0.001 score on a scale Standard Deviation 0.163
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 2	-0.003 score on a scale Standard Deviation 0.114	-0.030 score on a scale Standard Deviation 0.153
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 3	-0.014 score on a scale Standard Deviation 0.107	0.002 score on a scale Standard Deviation 0.188
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 4	-0.016 score on a scale Standard Deviation 0.111	-0.014 score on a scale Standard Deviation 0.209
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 7	-0.007 score on a scale Standard Deviation 0.078	0.002 score on a scale Standard Deviation 0.105
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 8	-0.016 score on a scale Standard Deviation 0.097	-0.028 score on a scale Standard Deviation 0.109
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 9	-0.024 score on a scale Standard Deviation 0.149	0.032 score on a scale Standard Deviation 0.085
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 10	-0.003 score on a scale Standard Deviation 0.094	0.018 score on a scale Standard Deviation 0.106
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 11	-0.008 score on a scale Standard Deviation 0.105	0.008 score on a scale Standard Deviation 0.104
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 12	-0.025 score on a scale Standard Deviation 0.113	0.030 score on a scale Standard Deviation 0.039
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 13	-0.037 score on a scale Standard Deviation 0.112	0.015 score on a scale
Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints Cycle 14	-0.034 score on a scale Standard Deviation 0.062	0.016 score on a scale

SECONDARY outcome

Timeframe: Baseline, Cycle 1, Cycle 2, Cycle 3, Cycle 4, Cycle 5, Cycle 6, Cycle 7, Cycle 8, Cycle 9, Cycle 10, Cycle 11, Cycle 12, Cycle 13 and Cycle 14

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

The EQ-5D-5L is a standardized measure of health status that provides a general assessment of health utility and consist of 2 sections; descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and a VAS. The VAS records the respondent's self-rated health on a 20 centimeter (cm) vertical VAS; the scale went from 0 (worst imaginable health state) to 100 (best imaginable health state). This information can be used as a quantitative measure of health as judged by the individual respondents.

Outcome measures

Measure	Trifluridine/Tipiracil + Bevacizumab n=201 Participants Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=207 Participants Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 1	2.095 score on a scale Standard Deviation 16.256	0.058 score on a scale Standard Deviation 15.749
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 2	0.852 score on a scale Standard Deviation 15.696	-4.242 score on a scale Standard Deviation 18.302
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 3	0.297 score on a scale Standard Deviation 17.618	-1.604 score on a scale Standard Deviation 15.729
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 4	-0.521 score on a scale Standard Deviation 18.177	-3.247 score on a scale Standard Deviation 17.769
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 5	1.904 score on a scale Standard Deviation 16.908	-1.271 score on a scale Standard Deviation 16.738
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 6	2.786 score on a scale Standard Deviation 16.162	-3.513 score on a scale Standard Deviation 18.602
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 7	1.500 score on a scale Standard Deviation 16.730	-2.708 score on a scale Standard Deviation 16.573
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 8	0.221 score on a scale Standard Deviation 15.635	-0.353 score on a scale Standard Deviation 16.328
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 9	-1.745 score on a scale Standard Deviation 14.085	3.400 score on a scale Standard Deviation 11.928
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 10	-1.953 score on a scale Standard Deviation 13.991	-4.500 score on a scale Standard Deviation 25.785
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 11	-1.212 score on a scale Standard Deviation 16.328	2.833 score on a scale Standard Deviation 16.388
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 12	2.385 score on a scale Standard Deviation 13.674	8.000 score on a scale Standard Deviation 15.188
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 13	-2.056 score on a scale Standard Deviation 15.757	13.000 score on a scale
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints Cycle 14	0.545 score on a scale Standard Deviation 15.952	13.000 score on a scale

Adverse Events

Trifluridine/Tipiracil + Bevacizumab

Serious events: 66 serious events

Other events: 241 other events

Deaths: 208 deaths

Trifluridine/Tipiracil

Serious events: 79 serious events

Other events: 241 other events

Deaths: 224 deaths

Serious adverse events

Measure	Trifluridine/Tipiracil + Bevacizumab n=246 participants at risk Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=246 participants at risk Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	2.4% 6/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	4.5% 11/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	1.6% 4/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to ovary	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Vascular disorders Deep vein thrombosis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Vascular disorders Hypertension	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
General disorders Asthenia	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
General disorders Pain	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
General disorders Fatigue	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	1.2% 3/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
General disorders Multiple organ dysfunction syndrome	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
General disorders Pyrexia	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
General disorders Death	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
General disorders General physical health deterioration	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
General disorders Malaise	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Immune system disorders Anaphylactic reaction	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Reproductive system and breast disorders Prostatitis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	1.6% 4/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea at rest	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Psychiatric disorders Confusional state	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Psychiatric disorders Psychomotor retardation	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Investigations Blood bilirubin increased	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Investigations Blood alkaline phosphatase increased	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Investigations C-reactive protein increased	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Investigations Gastrointestinal stoma output decreased	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Investigations Neutrophil count decreased	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Injury, poisoning and procedural complications Stoma site haemorrhage	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Injury, poisoning and procedural complications Spinal compression fracture	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Injury, poisoning and procedural complications Humerus fracture	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Injury, poisoning and procedural complications Gastrointestinal stoma complication	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Cardiac disorders Angina pectoris	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Cardiac disorders Atrial fibrillation	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Cardiac disorders Cardiac failure	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Cardiac disorders Cardiac failure congestive	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Cardiac disorders Pericardial effusion	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Cardiac disorders Pericarditis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Cardiac disorders Cardiac failure acute	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Nervous system disorders Balance disorder	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Nervous system disorders Dizziness	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Nervous system disorders Haemorrhagic stroke	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Nervous system disorders Headache	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Nervous system disorders Hypoaesthesia	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Nervous system disorders Cerebrovascular accident	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Nervous system disorders Diplegia	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Nervous system disorders Hepatic encephalopathy	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Blood and lymphatic system disorders Neutropenia	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Blood and lymphatic system disorders Anaemia	1.2% 3/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	3.7% 9/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Blood and lymphatic system disorders Febrile neutropenia	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	2.4% 6/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Blood and lymphatic system disorders Iron deficiency anaemia	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Blood and lymphatic system disorders Abdominal lymphadenopathy	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Eye disorders Glaucoma	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Intestinal obstruction	3.7% 9/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	2.0% 5/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Vomiting	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Abdominal pain	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Large intestinal obstruction	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Nausea	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Abdominal pain upper	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Ascites	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Ileus	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Subileus	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Abdominal hernia	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Anal fistula	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Abdominal tenderness	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Colitis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Gastrointestinal fistula	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Gastrointestinal perforation	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Intestinal perforation	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Large intestinal stenosis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	1.2% 3/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Constipation	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Gastritis haemorrhagic	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Hepatobiliary disorders Jaundice cholestatic	1.2% 3/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Hepatobiliary disorders Jaundice	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	2.0% 5/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Hepatobiliary disorders Cholangitis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Hepatobiliary disorders Bile duct stenosis	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Hepatobiliary disorders Biliary dilatation	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Hepatobiliary disorders Hyperbilirubinaemia	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Hepatobiliary disorders Bile duct stone	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Hepatobiliary disorders Cholecystitis acute	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Hepatobiliary disorders Hepatic failure	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	2.0% 5/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Hepatobiliary disorders Cholestasis	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Hepatobiliary disorders Hepatomegaly	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Renal and urinary disorders Acute kidney injury	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Renal and urinary disorders Pyelocaliectasis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Renal and urinary disorders Urinary incontinence	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Renal and urinary disorders Haematuria	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Renal and urinary disorders Prerenal failure	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Musculoskeletal and connective tissue disorders Muscular weakness	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations COVID-19	2.0% 5/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	2.4% 6/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Septic shock	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Pneumonia	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Urinary tract infection pseudomonal	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Vascular device infection	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Abdominal sepsis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations COVID-19 pneumonia	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Intestinal sepsis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Paracancerous pneumonia	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Peritonitis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Pneumonia streptococcal	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Postoperative abscess	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Pyelonephritis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Staphylococcal sepsis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Urinary tract infection bacterial	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Bacterial pyelonephritis	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Infection	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Abdominal infection	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Bacterial prostatitis	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Bronchitis	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Klebsiella sepsis	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Nasopharyngitis	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Pelvic abscess	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Sepsis	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Urinary tract infection	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations Urosepsis	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Metabolism and nutrition disorders Dehydration	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Metabolism and nutrition disorders Hypernatraemia	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Metabolism and nutrition disorders Cachexia	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.81% 2/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Gastrointestinal ischaemia	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Small intestinal stenosis	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Neutropenic colitis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Congenital, familial and genetic disorders Phimosis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Faecaloma	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Mechanical ileus	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Investigations Neutrophil count increased	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Duodenal stenosis	0.41% 1/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	0.00% 0/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.

Other adverse events

Measure	Trifluridine/Tipiracil + Bevacizumab n=246 participants at risk Participants were administered 35 mg/m²/dose FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest; with bevacizumab 5 mg/kg, IV infusion administered every 2 weeks (Day 1 and Day 15). This treatment cycle was repeated every 4 weeks.	Trifluridine/Tipiracil n=246 participants at risk Participants were administered 35 mg/m²/dose of FTD/TPI orally BID, within 1 hour after completion of morning and evening meals, 5 days on (Day 1 to 5 and Day 8 to 12) with 2 days off (Day 6 to 7 and Day 13 to 14), over 2 weeks, followed by a 14-day rest. This treatment cycle was repeated every 4 weeks.
Investigations Neutrophil count decreased	13.8% 34/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	7.3% 18/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Investigations Platelet count decreased	9.8% 24/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	2.4% 6/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Investigations Alanine aminotransferase increased	8.1% 20/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	5.7% 14/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Investigations Aspartate aminotransferase increased	8.1% 20/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	5.7% 14/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Investigations Weight decreased	9.3% 23/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	4.9% 12/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Investigations Blood bilirubin increased	6.5% 16/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	5.7% 14/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Vascular disorders Hypertension	10.6% 26/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	2.0% 5/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Nervous system disorders Headache	8.5% 21/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	3.7% 9/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Blood and lymphatic system disorders Neutropenia	62.2% 153/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	51.2% 126/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Blood and lymphatic system disorders Anaemia	32.1% 79/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	32.5% 80/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Blood and lymphatic system disorders Thrombocytopenia	17.9% 44/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	11.8% 29/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Blood and lymphatic system disorders Leukopenia	7.7% 19/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	8.5% 21/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
General disorders Asthenia	24.8% 61/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	23.6% 58/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
General disorders Fatigue	22.0% 54/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	16.7% 41/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
General disorders Pyrexia	6.1% 15/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	5.7% 14/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Nausea	38.6% 95/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	28.0% 69/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Diarrhoea	22.0% 54/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	19.1% 47/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Vomiting	20.7% 51/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	14.6% 36/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Abdominal pain	12.6% 31/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	11.0% 27/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Constipation	11.4% 28/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	11.4% 28/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Stomatitis	11.8% 29/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	4.1% 10/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Gastrointestinal disorders Abdominal pain upper	9.3% 23/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	4.5% 11/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Renal and urinary disorders Proteinuria	6.1% 15/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	1.6% 4/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Musculoskeletal and connective tissue disorders Arthralgia	7.3% 18/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	2.4% 6/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Musculoskeletal and connective tissue disorders Back pain	7.7% 19/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	5.3% 13/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Metabolism and nutrition disorders Decreased appetite	22.4% 55/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	15.9% 39/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.
Infections and infestations COVID-19	9.8% 24/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.	4.1% 10/246 • Serious AEs and Other AEs: From baseline (Cycle 1 Day 1) up to 30 days after the last dose of study drug (i.e., up to 30.7 months); All-cause mortality: from baseline (Cycle 1 Day 1) up to end of the study (i.e., up to 33.6 months) Analysis was performed on safety set population which included all participants who took at least one dose of FTD/TPI and were analyzed according to the treatment actually received. Reported serious AEs and other AEs were treatment-emergent AEs that developed, worsened or became serious from baseline (Cycle 1 Day 1) up to 30 days after the last dose of the study drug.

Additional Information

Taiho

Taiho Oncology, Inc.

Phone: +1-844-878-2446

Email: medicalinformation@taihooncology.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER