Trial Outcomes & Findings for Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer (mCRC): (NCT NCT04607668)

NCT ID: NCT04607668

Last Updated: 2024-11-26

Results Overview

The DSN was defined as the number of days for the first severe neutropenia (SN) event in Cycles 1, 2, 3, or 4 for participants who had at least one SN event in the first 4 cycles of Induction. It was calculated as the days from the date of the first absolute neutrophil count (ANC) value of \< 0.5 × 10\^9/L to the date of the first ANC value ≥ 0.5 × 10\^9/L where no additional ANC values \< 0.5 × 10\^9/L were observed for the remainder of that cycle.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 326 participants
• Primary outcome timeframe: Cycles 1 to 4 (14-day cycles up to 56 days)
• Results posted on: 2024-11-26

Participant Flow

89 study centers in 8 countries consented at least 1 participant. The first participant was enrolled on January 6, 2021 and the last visit of the last participant occurred on March 31, 2023.

A total of 458 participants were screened in this study. 326 participants were randomized in a double-blind manner to receive either trilaciclib or placebo, administered on Days 1 and 2 of each cycle of FOLFOXIRI and bevacizumab therapy. A total of 319 participants received at least 1 dose of study drug.

Participant milestones

Measure	Trilaciclib + FOLFOXIRI/Bevacizumab During Induction the following study drugs were administered on Day 1: Trilaciclib - IV infusion prior to chemotherapy Irinotecan- IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil (5-FU) - continuous infusion (CI) over 46-48 hours beginning on Day 1, Bevacizumab - IV The Induction Day 1 administration of trilaciclib was repeated on Induction Day 2. Following completion of Induction, patients continued in Maintenance, where they continued to receive trilaciclib per randomization allocation. Trilaciclib was administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Placebo + FOLFOXIRI/Bevacizumab The subjects in the placebo arm followed the same schedule as the trilaciclib arm, but received placebo instead of trilaciclib Placebo: dextrose 5% in water or normal saline (sodium chloride solution 0.9%)
Overall Study STARTED	164	162
Overall Study Patients With ≥ 1 Dose of Study Drug, n (%)	159	160
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	164	162

Reasons for withdrawal

Measure	Trilaciclib + FOLFOXIRI/Bevacizumab During Induction the following study drugs were administered on Day 1: Trilaciclib - IV infusion prior to chemotherapy Irinotecan- IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil (5-FU) - continuous infusion (CI) over 46-48 hours beginning on Day 1, Bevacizumab - IV The Induction Day 1 administration of trilaciclib was repeated on Induction Day 2. Following completion of Induction, patients continued in Maintenance, where they continued to receive trilaciclib per randomization allocation. Trilaciclib was administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Placebo + FOLFOXIRI/Bevacizumab The subjects in the placebo arm followed the same schedule as the trilaciclib arm, but received placebo instead of trilaciclib Placebo: dextrose 5% in water or normal saline (sodium chloride solution 0.9%)
Overall Study Other, unspecified	8	7
Overall Study Death	49	26
Overall Study Lost to Follow-up	3	4
Overall Study Study terminated by Sponsor	92	114
Overall Study Withdrawal by Subject	12	11

Baseline Characteristics

Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving FOLFOXIRI/Bevacizumab for Metastatic Colorectal Cancer (mCRC):

Baseline characteristics by cohort

Measure	Trilaciclib + FOLFOXIRI/Bevacizumab n=164 Participants During Induction the following study drugs were administered on Day 1: Trilaciclib - IV infusion prior to chemotherapy Irinotecan- IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil (5-FU) - continuous infusion (CI) over 46-48 hours beginning on Day 1, Bevacizumab - IV The Induction Day 1 administration of trilaciclib was repeated on Induction Day 2. Following completion of Induction, patients continued in Maintenance, where they continued to receive trilaciclib per randomization allocation. Trilaciclib was administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Placebo + FOLFOXIRI/Bevacizumab n=162 Participants The subjects in the placebo arm followed the same schedule as the trilaciclib arm, but received placebo instead of trilaciclib Placebo: dextrose 5% in water or normal saline (sodium chloride solution 0.9%)	Total n=326 Participants Total of all reporting groups
Age, Continuous	56.2 Years STANDARD_DEVIATION 11.80 • n=5 Participants	55.5 Years STANDARD_DEVIATION 10.60 • n=7 Participants	55.8 Years STANDARD_DEVIATION 11.21 • n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	61 Participants n=7 Participants	119 Participants n=5 Participants
Sex: Female, Male Male	106 Participants n=5 Participants	101 Participants n=7 Participants	207 Participants n=5 Participants
Race/Ethnicity, Customized White	119 Participants n=5 Participants	112 Participants n=7 Participants	231 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Asian	32 Participants n=5 Participants	33 Participants n=7 Participants	65 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycles 1 to 4 (14-day cycles up to 56 days)

Population: A Modified Intent-to-Treat (mITT) population was utilized in order to account for potential data integrity issues resulting from the war in Ukraine. The criteria for patients to be included in the mITT population consisted of all patients being randomized in countries other than Ukraine and all patients in Ukraine being randomized prior to 09 September 2021.

The DSN was defined as the number of days for the first severe neutropenia (SN) event in Cycles 1, 2, 3, or 4 for participants who had at least one SN event in the first 4 cycles of Induction. It was calculated as the days from the date of the first absolute neutrophil count (ANC) value of < 0.5 × 10^9/L to the date of the first ANC value ≥ 0.5 × 10^9/L where no additional ANC values < 0.5 × 10^9/L were observed for the remainder of that cycle.

Outcome measures

Measure	Trilaciclib + FOLFOXIRI/Bevacizumab n=149 Participants During Induction the following study drugs were administered on Day 1: Trilaciclib - IV infusion prior to chemotherapy Irinotecan- IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil (5-FU) - continuous infusion (CI) over 46-48 hours beginning on Day 1, Bevacizumab - IV The Induction Day 1 administration of trilaciclib was repeated on Induction Day 2. Following completion of Induction, patients continued in Maintenance, where they continued to receive trilaciclib per randomization allocation. Trilaciclib was administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Placebo + FOLFOXIRI/Bevacizumab n=147 Participants The subjects in the placebo arm followed the same schedule as the trilaciclib arm, but received placebo instead of trilaciclib Placebo: dextrose 5% in water or normal saline (sodium chloride solution 0.9%)
Duration of Severe Neutropenia (DSN)	0.1 days Standard Deviation 0.84	1.3 days Standard Deviation 3.14

PRIMARY outcome

Timeframe: Induction Period, cycles 1-12 (14-day cycles up to 168 days)

Population: A Modified Intent-to-Treat (mITT) population was utilized in order to account for potential data integrity issues resulting from the war in Ukraine. The criteria for patients to be included in the mITT population consisted of all patients being randomized in countries other than Ukraine and all patients in Ukraine being randomized prior to 09 September 2021.

Severe neutropenia was defined as the absolute neutrophil count (ANC) laboratory value that met the Common Terminology Criteria for Adverse vents (CTCAE) criteria for ≥ Grade 4 toxicity (ie, ANC < 0.5 × 10^9/L in SI Unit)

Outcome measures

Measure	Trilaciclib + FOLFOXIRI/Bevacizumab n=149 Participants During Induction the following study drugs were administered on Day 1: Trilaciclib - IV infusion prior to chemotherapy Irinotecan- IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil (5-FU) - continuous infusion (CI) over 46-48 hours beginning on Day 1, Bevacizumab - IV The Induction Day 1 administration of trilaciclib was repeated on Induction Day 2. Following completion of Induction, patients continued in Maintenance, where they continued to receive trilaciclib per randomization allocation. Trilaciclib was administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Placebo + FOLFOXIRI/Bevacizumab n=147 Participants The subjects in the placebo arm followed the same schedule as the trilaciclib arm, but received placebo instead of trilaciclib Placebo: dextrose 5% in water or normal saline (sodium chloride solution 0.9%)
Occurrence of Severe Neutropenia (SN) During Induction	0.1 event per 100 cycles	3 event per 100 cycles

SECONDARY outcome

Timeframe: Up to 52 months

Population: Due to early study termination, data were not collected for this outcome measure.

Overall survival is defined as the time from the date of the first dose of study treatment to the date of death from any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through Induction Period - on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab

Population: Due to early study termination, data were not collected for this outcome measure.

To assess the effects of trilaciclib on additional measures of the neutrophil lineage compared with placebo in patients receiving FOLFOXIRI/bevacizumab for pMMR/MSS mCRC as measured by the number of SN events, granulocyte-colony stimulating factor (G-CSF) administration and febrile neutropenia (FN) adverse events (AE)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through Induction Period - on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab

Population: Due to early study termination, data were not collected for this outcome measure.

To assess the effects of trilaciclib on the red blood cell (RBC) lineage compared with placebo in patients receiving FOLFOXIRI/bevacizumab for pMMR/MSS mCRC by measure of Grade 3 or 4 decreased hemoglobin laboratory values, RBC transfusions on or after Week 5, and erythropoiesis-stimulating agents (ESA) administration

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through Induction Period - on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab

Population: Due to early study termination, data were not collected for this outcome measure.

To assess the effects of trilaciclib on the platelet lineage compared with placebo in patients receiving FOLFOXIRI/bevacizumab for pMMR/MSS mCR by measure of Grade 3 or 4 decreased platelet count laboratory values and Platelet transfusions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through Induction Period - on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab

Population: Due to early study termination, data were not collected for this outcome measure.

To assess the effects of trilaciclib on multiple lineages compared with placebo in patients receiving FOLFOXIRI/bevacizumab for pMMR/MSS mCRC by measure of Grade 3 or 4 hematologic lab values.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through Induction Period - on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab

Population: Due to early study termination, data were not collected for this outcome measure.

To assess the effects of trilaciclib on standard of care dosing compared with placebo in patients receiving FOLFOXIRI/ bevacizumab for pMMR/MSS mCRC by measure of all-cause dose reductions or cycle delays and relative dose intensity for FOLFOXIRI/bevacizumab

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through Induction Period - on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab

Population: Due to early study termination, data were not collected for this outcome measure.

To assess the effects of trilaciclib on healthcare utilization compared with placebo in patients receiving FOLFOXIRI/ bevacizumab for pMMR/MSS mCRC by measure of hospitalizations and antibiotic use.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Through Induction Period - on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab

Population: The Response Evaluable (RE) population included those patients in the mITT population who received at least 1 dose of any study drug and had measurable (target) tumor lesion(s) at the baseline tumor assessment. The patients also had at least 1 post-baseline tumor assessment, discontinued treatment because of clinical progression prior to their first post-baseline tumor scan, or died due to disease progression prior to their first post-baseline tumor scan.

Best overall response (BOR) will be determined using all visit responses prior to or on the date of (i) radiographic disease progression; (ii) withdrawal of consent to obtain scans; (iii) death; (iv) lost to follow-up; or (v) initiation of subsequent anti-cancer therapy other than the study drugs, whichever is earlier will be based on RECIST v1.1.

Outcome measures

Measure	Trilaciclib + FOLFOXIRI/Bevacizumab n=137 Participants During Induction the following study drugs were administered on Day 1: Trilaciclib - IV infusion prior to chemotherapy Irinotecan- IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil (5-FU) - continuous infusion (CI) over 46-48 hours beginning on Day 1, Bevacizumab - IV The Induction Day 1 administration of trilaciclib was repeated on Induction Day 2. Following completion of Induction, patients continued in Maintenance, where they continued to receive trilaciclib per randomization allocation. Trilaciclib was administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Placebo + FOLFOXIRI/Bevacizumab n=140 Participants The subjects in the placebo arm followed the same schedule as the trilaciclib arm, but received placebo instead of trilaciclib Placebo: dextrose 5% in water or normal saline (sodium chloride solution 0.9%)
Best Overall Response (BOR) Complete response	0 percentage of participants	3 percentage of participants
Best Overall Response (BOR) Partial response	75 percentage of participants	91 percentage of participants
Best Overall Response (BOR) Stable disease	50 percentage of participants	36 percentage of participants
Best Overall Response (BOR) Progressive disease	5 percentage of participants	7 percentage of participants
Best Overall Response (BOR) Not evaluable	7 percentage of participants	3 percentage of participants

SECONDARY outcome

Timeframe: Assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks

Population: The Response Evaluable (RE) population included those patients in the mITT population who received at least 1 dose of any study drug and had measurable (target) tumor lesion(s) at the baseline tumor assessment. The patients also had at least 1 post-baseline tumor assessment, discontinued treatment because of clinical progression prior to their first post-baseline tumor scan, or died due to disease progression prior to their first post-baseline tumor scan.

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR) defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to <10 mm or Partial Response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference based on RECIST v1.1.

Outcome measures

Measure	Trilaciclib + FOLFOXIRI/Bevacizumab n=137 Participants During Induction the following study drugs were administered on Day 1: Trilaciclib - IV infusion prior to chemotherapy Irinotecan- IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil (5-FU) - continuous infusion (CI) over 46-48 hours beginning on Day 1, Bevacizumab - IV The Induction Day 1 administration of trilaciclib was repeated on Induction Day 2. Following completion of Induction, patients continued in Maintenance, where they continued to receive trilaciclib per randomization allocation. Trilaciclib was administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Placebo + FOLFOXIRI/Bevacizumab n=140 Participants The subjects in the placebo arm followed the same schedule as the trilaciclib arm, but received placebo instead of trilaciclib Placebo: dextrose 5% in water or normal saline (sodium chloride solution 0.9%)
Objective Response Rate (ORR)	41.6 percentage of participants Interval 33.3 to 50.3	57.1 percentage of participants Interval 48.5 to 65.5

SECONDARY outcome

Timeframe: Assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks

Population: The Response Evaluable (RE) population included those patients in the mITT population who received at least 1 dose of any study drug and had measurable (target) tumor lesion(s) at the baseline tumor assessment. The patients also had at least 1 post-baseline tumor assessment, discontinued treatment because of clinical progression prior to their first post-baseline tumor scan, or died due to disease progression prior to their first post-baseline tumor scan.

DOR is the time between first objective response of CR or PR and the first date that progressive disease is objectively documented or death, whichever comes first.

Outcome measures

Measure	Trilaciclib + FOLFOXIRI/Bevacizumab n=137 Participants During Induction the following study drugs were administered on Day 1: Trilaciclib - IV infusion prior to chemotherapy Irinotecan- IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil (5-FU) - continuous infusion (CI) over 46-48 hours beginning on Day 1, Bevacizumab - IV The Induction Day 1 administration of trilaciclib was repeated on Induction Day 2. Following completion of Induction, patients continued in Maintenance, where they continued to receive trilaciclib per randomization allocation. Trilaciclib was administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Placebo + FOLFOXIRI/Bevacizumab n=140 Participants The subjects in the placebo arm followed the same schedule as the trilaciclib arm, but received placebo instead of trilaciclib Placebo: dextrose 5% in water or normal saline (sodium chloride solution 0.9%)
Duration of Objective Response (DOR)	9.1 months Interval 7.9 to 10.2	12.7 months Interval 9.5 to The upper limit of the 95% Confidence Interval was not estimable due to insufficient participants with events.

SECONDARY outcome

Timeframe: Assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks

Population: Modified Intent-to-Treat (mITT) population was utilized in order to account for potential data integrity issues resulting from the war in Ukraine. The criteria for patients to be included in the mITT population consisted of all patients being randomized in countries other than Ukraine and all patients in Ukraine being randomized prior to 09 September 2021.

PFS is defined as the time from the date of randomization until the date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever comes first.

Outcome measures

Measure	Trilaciclib + FOLFOXIRI/Bevacizumab n=149 Participants During Induction the following study drugs were administered on Day 1: Trilaciclib - IV infusion prior to chemotherapy Irinotecan- IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil (5-FU) - continuous infusion (CI) over 46-48 hours beginning on Day 1, Bevacizumab - IV The Induction Day 1 administration of trilaciclib was repeated on Induction Day 2. Following completion of Induction, patients continued in Maintenance, where they continued to receive trilaciclib per randomization allocation. Trilaciclib was administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Placebo + FOLFOXIRI/Bevacizumab n=147 Participants The subjects in the placebo arm followed the same schedule as the trilaciclib arm, but received placebo instead of trilaciclib Placebo: dextrose 5% in water or normal saline (sodium chloride solution 0.9%)
Progression Free Survival (PFS)	10.3 months Interval 8.6 to 11.0	13.1 months Interval 11.0 to 18.5

SECONDARY outcome

Timeframe: Through Induction Period- on average 24 weeks (up to 12 cycles) of FOLFOXIRI/bevacizumab

Population: Due to early study termination, data were not collected for this outcome measure.

To assess the effects of trilaciclib on chemotherapy-induced fatigue compared with placebo in patients receiving FOLFOXIRI/bevacizumab for pMMR/MSS mCRC, as measured by Time To First Confirmed Deterioration of Fatigue (TTCD-fatigue) during Induction, as measured by the FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks

Population: The Safety population included all randomized patients who received at least 1 dose of any study drug.

To assess the safety and tolerability of trilaciclib compared with placebo in patients receiving FOLFOXIRI/ bevacizumab for pMMR/MSS mCRC by measure of occurrence and severity of AEs by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, changes in laboratory parameters, vital signs and electrocardiogram (ECG) parameters, grade 3 or 4 abnormalities in chemistry laboratory parameters, and study treatment discontinuation due to AEs.

Outcome measures

Measure	Trilaciclib + FOLFOXIRI/Bevacizumab n=159 Participants During Induction the following study drugs were administered on Day 1: Trilaciclib - IV infusion prior to chemotherapy Irinotecan- IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil (5-FU) - continuous infusion (CI) over 46-48 hours beginning on Day 1, Bevacizumab - IV The Induction Day 1 administration of trilaciclib was repeated on Induction Day 2. Following completion of Induction, patients continued in Maintenance, where they continued to receive trilaciclib per randomization allocation. Trilaciclib was administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Placebo + FOLFOXIRI/Bevacizumab n=160 Participants The subjects in the placebo arm followed the same schedule as the trilaciclib arm, but received placebo instead of trilaciclib Placebo: dextrose 5% in water or normal saline (sodium chloride solution 0.9%)
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Number of patients with any AE	157 Participants	159 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Number of patients with any AE of CTCAE Grade ≥ 3	106 Participants	117 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Number of patients with any AE of CTCAE Grade ≥ 4	18 Participants	35 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Number of patients with any study drug-related AE	154 Participants	155 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Trilaciclib/Placebo-Related AE	109 Participants	103 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Fluorouracil-related AE	139 Participants	151 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Leucovorin-related AE	103 Participants	122 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Oxaliplatin-related AE	143 Participants	151 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Irinotecan-related AE	143 Participants	151 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Bevacizumab-related AE	127 Participants	128 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Patients with any serious AE	47 Participants	47 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Patients with AE leading to discontinuation of any study drug	50 Participants	47 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Leading to trilaciclib/placebo discontinuation	19 Participants	13 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Leading to fluorouracil discontinuation	19 Participants	14 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Leading to leucovorin discontinuation	20 Participants	13 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Leading to oxaliplatin discontinuation	38 Participants	30 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Leading to irinotecan discontinuation	20 Participants	20 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Leading to bevacizumab discontinuation	31 Participants	26 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Patients with trilaciclib/placebo-related AE leading to discontinuation of any study drug	10 Participants	9 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Patients with AE leading to death	8 Participants	3 Participants
Number of Participants With Reported Adverse Events to Measure Safety and Tolerability Patients with AESI for trilaciclib	33 Participants	28 Participants

Adverse Events

Trilaciclib + FOLFOXIRI/Bevacizumab

Serious events: 47 serious events

Other events: 155 other events

Deaths: 49 deaths

Placebo + FOLFOXIRI/Bevacizumab

Serious events: 47 serious events

Other events: 159 other events

Deaths: 26 deaths

Serious adverse events

Measure	Trilaciclib + FOLFOXIRI/Bevacizumab n=159 participants at risk During Induction the following study drugs were administered on Day 1: Trilaciclib - IV infusion prior to chemotherapy Irinotecan- IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil (5-FU) - continuous infusion (CI) over 46-48 hours beginning on Day 1, Bevacizumab - IV The Induction Day 1 administration of trilaciclib was repeated on Induction Day 2. Following completion of Induction, patients continued in Maintenance, where they continued to receive trilaciclib per randomization allocation. Trilaciclib was administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Placebo + FOLFOXIRI/Bevacizumab n=160 participants at risk The subjects in the placebo arm followed the same schedule as the trilaciclib arm, but received placebo instead of trilaciclib Placebo: dextrose 5% in water or normal saline (sodium chloride solution 0.9%)
Blood and lymphatic system disorders Anaemia	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	1.2% 2/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	3.1% 5/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Blood and lymphatic system disorders Leukopenia	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Blood and lymphatic system disorders Neutropenia	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	3.1% 5/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Blood and lymphatic system disorders Pancytopenia	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Cardiac disorders Acute myocardial infarction	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Cardiac disorders Cardiac failure acute	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Cardiac disorders Left ventricular dysfunction	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Cardiac disorders Myocardial injury	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Cardiac disorders Ventricular tachycardia	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Abdominal adhesions	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Abdominal pain	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	1.9% 3/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Anal fistula	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Colitis	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Constipation	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Diarrhoea	1.3% 2/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	1.9% 3/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Enterocutaneous fistula	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Gastrointestinal obstruction	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Ileus	1.3% 2/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Ileus paralytic	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Intestinal obstruction	2.5% 4/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	1.9% 3/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Intestinal perforation	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Large intestine perforation	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Nausea	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Oesophageal rupture	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Rectal haemorrhage	1.3% 2/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Rectal perforation	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Small intestinal obstruction	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Subileus	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Vomiting	1.9% 3/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	1.2% 2/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
General disorders Death	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
General disorders Device related thrombosis	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
General disorders Pain	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
General disorders Pyrexia	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	1.9% 3/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Immune system disorders Drug hypersensitivity	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Abdominal abscess	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Abscess limb	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Anal abscess	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Anorectal infection	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Appendicitis	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations COVID-19	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations COVID-19 pneumonia	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Cellulitis	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	1.2% 2/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Device related infection	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Infectious pleural effusion	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Intestinal sepsis	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Neutropenic sepsis	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Pelvic abscess	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Pneumonia	1.9% 3/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Pyelonephritis	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Sepsis	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	1.9% 3/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Injury, poisoning and procedural complications Drain site complication	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Investigations Alanine aminotransferase increased	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	1.2% 2/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Investigations Aspartate aminotransferase increased	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Investigations Blood bilirubin increased	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Investigations Gamma-glutamyltransferase increased	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Hyperglycaemia	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Hypocalcaemia	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Hypokalaemia	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Hypomagnesaemia	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Myopathy	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal carcinoma	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Dizziness	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Ischaemic stroke	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Lumbar radiculopathy	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Myoclonic epilepsy	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Seizure	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Syncope	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Psychiatric disorders Anxiety	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Psychiatric disorders Completed suicide	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Renal and urinary disorders Acute kidney injury	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Renal and urinary disorders Urinary retention	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	1.2% 2/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.5% 4/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	2.5% 4/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary thrombosis	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.3% 2/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Vascular disorders Aortic embolus	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.00% 0/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Vascular disorders Embolism	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Vascular disorders Hypertension	0.63% 1/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Vascular disorders Jugular vein thrombosis	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Vascular disorders Superior vena cava syndrome	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Vascular disorders Thrombosis	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Vascular disorders Venous thrombosis	0.00% 0/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	1.2% 2/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.

Other adverse events

Measure	Trilaciclib + FOLFOXIRI/Bevacizumab n=159 participants at risk During Induction the following study drugs were administered on Day 1: Trilaciclib - IV infusion prior to chemotherapy Irinotecan- IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil (5-FU) - continuous infusion (CI) over 46-48 hours beginning on Day 1, Bevacizumab - IV The Induction Day 1 administration of trilaciclib was repeated on Induction Day 2. Following completion of Induction, patients continued in Maintenance, where they continued to receive trilaciclib per randomization allocation. Trilaciclib was administered prior to infusional-5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Placebo + FOLFOXIRI/Bevacizumab n=160 participants at risk The subjects in the placebo arm followed the same schedule as the trilaciclib arm, but received placebo instead of trilaciclib Placebo: dextrose 5% in water or normal saline (sodium chloride solution 0.9%)
Blood and lymphatic system disorders Anaemia	35.8% 57/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	38.1% 61/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Blood and lymphatic system disorders Leukopenia	17.0% 27/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	21.9% 35/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Blood and lymphatic system disorders Neutropenia	38.4% 61/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	57.5% 92/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Blood and lymphatic system disorders Thrombocytopenia	21.4% 34/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	22.5% 36/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Abdominal distension	5.7% 9/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	3.8% 6/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Abdominal pain	21.4% 34/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	22.5% 36/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Abdominal pain upper	5.7% 9/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	5.0% 8/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Constipation	23.9% 38/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	18.1% 29/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Diarrhoea	52.2% 83/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	73.8% 118/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Dyspepsia	6.9% 11/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	6.2% 10/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	6.3% 10/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	3.8% 6/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Haemorrhoids	3.1% 5/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	6.9% 11/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Nausea	53.5% 85/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	63.1% 101/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Oral dysaesthesia	3.1% 5/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	5.0% 8/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Rectal haemorrhage	4.4% 7/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	5.6% 9/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Stomatitis	15.7% 25/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	26.2% 42/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Gastrointestinal disorders Vomiting	34.0% 54/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	40.0% 64/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
General disorders Asthenia	17.6% 28/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	17.5% 28/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
General disorders Fatigue	33.3% 53/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	32.5% 52/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
General disorders Mucosal inflammation	10.7% 17/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	11.2% 18/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
General disorders Pyrexia	10.7% 17/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	13.8% 22/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
General disorders Temperature intolerance	6.3% 10/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	3.1% 5/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations COVID-19	11.3% 18/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	13.8% 22/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Upper respiratory tract infection	4.4% 7/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	7.5% 12/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Infections and infestations Urinary tract infection	6.9% 11/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	6.2% 10/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Investigations Alanine aminotransferase increased	12.6% 20/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	15.0% 24/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Investigations Aspartate aminotransferase increased	12.6% 20/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	15.0% 24/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Investigations Blood alkaline phosphatase increased	8.2% 13/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	6.9% 11/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Investigations Gamma-glutamyltransferase increased	5.7% 9/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	5.6% 9/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Investigations Neutrophil count decreased	7.5% 12/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	9.4% 15/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Investigations Platelet count decreased	5.7% 9/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	4.4% 7/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Investigations Weight decreased	12.6% 20/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	18.1% 29/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Investigations White blood cell count decreased	5.0% 8/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	7.5% 12/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Decreased appetite	22.6% 36/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	24.4% 39/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Dehydration	7.5% 12/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	6.9% 11/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Hyperglycaemia	6.9% 11/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	5.0% 8/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	3.8% 6/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	6.9% 11/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Hypokalaemia	13.2% 21/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	13.1% 21/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Hypomagnesaemia	5.7% 9/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	1.9% 3/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Hypophosphataemia	3.8% 6/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	7.5% 12/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Arthralgia	5.7% 9/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	8.1% 13/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Back pain	5.7% 9/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	6.9% 11/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	12.6% 20/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	5.6% 9/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	5.0% 8/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	3.8% 6/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Dizziness	8.2% 13/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	11.9% 19/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Dysgeusia	7.5% 12/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	6.2% 10/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Headache	20.1% 32/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	16.2% 26/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Neuropathy peripheral	22.6% 36/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	16.2% 26/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Neurotoxicity	6.3% 10/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	8.1% 13/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Paraesthesia	12.6% 20/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	9.4% 15/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Peripheral sensory neuropathy	23.3% 37/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	21.2% 34/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Nervous system disorders Tremor	5.0% 8/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	0.62% 1/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Psychiatric disorders Anxiety	8.2% 13/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	7.5% 12/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Psychiatric disorders Insomnia	9.4% 15/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	9.4% 15/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Renal and urinary disorders Proteinuria	11.9% 19/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	15.6% 25/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Cough	8.2% 13/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	7.5% 12/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.9% 11/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	5.0% 8/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	4.4% 7/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	17.5% 28/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Hiccups	8.8% 14/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	5.6% 9/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.3% 10/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	3.8% 6/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.1% 5/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	5.0% 8/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.5% 4/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	6.2% 10/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Skin and subcutaneous tissue disorders Alopecia	14.5% 23/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	15.6% 25/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	2.5% 4/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	5.0% 8/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Vascular disorders Hypertension	21.4% 34/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	21.9% 35/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.
Vascular disorders Hypotension	3.1% 5/159 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.	5.0% 8/160 • Safety was assessed from the day of the first dose of the study drug, through 30 days after the last dose of the study drug, up to 115 weeks. Analysis was performed on the Safety analysis set which included all randomized participants who received at least one dose of any study drug.

Additional Information

Clinical Trial Info

G1 Therapeutics, Inc

Phone: +1 9192139835

Email: clinicalinfo@g1therapeutics.com

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