Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving F... | NCT04607668

Label	Type	Description	Intervention Names
trilaciclib + FOLFOXIRI/bevacizumab	Experimental	During Induction the following study drugs are administered on Day 1: Irinotecan - IV, Oxaliplatin - IV, Leucovorin- IV, Fluorouracil - continuous infusion (CI) over 46 to 48 hours beginning on Day 1, Bevacizumab - IV Following completion of Induction, patients will continue in Maintenance, where they will continue to receive trilaciclib per randomization allocation at study entry. Trilaciclib will be administered prior to infusional- 5FU/leucovorin/bevacizumab at the same dose and schedule used during Induction.	Drug: Trilaciclib
placebo + FOLFOXIRI/bevacizumab	Placebo Comparator	The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Trilaciclib	Drug	Trilaciclib diluted in dextrose 5% in water or normal saline (sodium chloride solution 0.9%) administered by IV infusion over approximately 30 (±10) minutes no more than 4 hours prior to each Day 1 chemotherapy administration. Second dose of trilaciclib was administered on Day 2.

Measure	Description	Time Frame
Duration of Severe Neutropenia (DSN)	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.	Cycles 1 to 4 (14-day cycles up to 56 days)
Occurrence of Severe Neutropenia (SN) During Induction	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)	Induction Period, cycles 1-12 (14-day cycles up to 168 days)

Measure	Description	Time Frame
Overall Survival (OS)	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.	Up to 52 months
Additional Myelopreservation Measures

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥ 18 years of age at the time of signing the informed consent. Patients > 70 years of age must have a G8 Health State Screening Tool (geriatric screening tool) score > 14.
Proficient mismatch repair/microsatellite stable (pMMR/MSS), histologically or cytologically-confirmed adenocarcinoma of the colon or rectum. Patients with any BRAF or KRAS mutation status (wild type or mutant) are eligible. If historical pMMR/MSS and/or BRAF V600E mutational status are not known, a tumor specimen (archival or fresh biopsy) must be sent for testing and results must be available at the time of randomization in interactive web response system (IWRS). If testing cannot be completed using a standard clinical assay performed institutionally/locally, the tumor specimen may be sent to the Sponsor's designated central laboratory for analysis; only historical KRAS mutational status will be collected (ie, no testing required prior to study entry). Note: Any sample sent for MSS/BRAF analysis will be in addition to that required per Inclusion Criterion 5.
Unresectable and measurable or metastatic colorectal cancer per RECIST v1.1
ECOG performance status of 0 to 1
A formalin-fixed paraffin-embedded (FFPE) tumor specimen (from archival or fresh biopsy) with an associated pathology report documenting pMMR/MSS mCRC must be confirmed to be available to send to the Sponsor for planned retrospective biomarker analyses (tissue requirements are provided in the associated laboratory manual).
Hemoglobin ≥ 9.0 g/dL in the absence of RBC transfusion or ESA administration within 14 days prior to first dose of trilaciclib/placebo
Absolute neutrophil count (ANC) ≥ 1.5 × 10^9 /L
Platelet count ≥ 100 × 10^9 /L
Estimated glomerular filtration rate (eGFR) ≥ 30 mL/minute/1.73m^2
Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
AST, ALT, and alkaline phosphatase ≤ 3 × ULN for patients without liver or bone metastases; AST, ALT and alkaline phosphatase ≤ 5 × ULN in the presence of liver metastases; AST and ALT ≤ 3 x ULN and alkaline phosphatase ≤ 5 × ULN in the presence of bone metastases
Resolution of nonhematologic toxicities from prior therapy or surgical procedures to ≤ Grade 1 or baseline (except alopecia)
Urine dipstick protein < 2+. If ≥ 2+ at Screening, then a 24-hour urine collection must be done to demonstrate ≤ 1 g of protein/24 hours
Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Please see Section 17.4 for detailed instructions on methods of contraception requirements.
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

Prior systemic therapy for mCRC. Patients who received adjuvant/neoadjuvant therapy (ie, treatment with curative intent) for colorectal cancer are eligible if it has been ≥ 6 months between the last dose of systemic chemotherapy and the date of informed consent.
Any radiotherapy, chemotherapy, immunotherapy, biologic, investigational, or hormonal therapy for cancer treatment (except for adjuvant hormonal therapy for breast cancer or prostate cancer defined as M0 disease or PSA persistence/recurrence without metastatic disease) within 3 weeks prior to the first dose of trilaciclib/placebo.
Receipt of any low-dose systemic chemotherapeutic agent (e.g., low-dose methotrexate for rheumatoid arthritis) administered for a nononcologic purpose within 3 weeks prior to the first dose of trilaciclib/placebo.
Presence of central nervous system (CNS) metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids (i.e., patient must be off steroids administered for brain metastases for at least 14 days prior to the first dose of trilaciclib/placebo).
QTcF interval > 450 msec (males) or > 470 msec (females) at screening. For patients with ventricular pacemakers, QTcF > 500 msec.
Personal or family history of long QT syndrome
Symptomatic peripheral neuropathy
History of interstitial lung disease (ILD)
Uncontrolled hypertension (blood pressure ≥ 150/90mm Hg)
Clinically significant (i.e., active) cardiovascular disease at the time of signing the informed consent; for example cerebrovascular accidents (≤ 6 months before the first dose of trilaciclib/placebo), myocardial infarction (≤ 6 months before the first dose of trilaciclib/placebo), unstable angina, serious cardiac arrhythmia requiring medication, or uncontrolled symptomatic congestive heart failure [Class II or higher as defined by the New York Heart Association [NYHA] functional classification system])
Serious, non-healing wound, ulcer, or bone fracture
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
Known serious active infection (e.g., human immunodeficiency virus [HIV], hepatitis B or C, tuberculosis, etc.)
Known Gilbert's Syndrome or homozygous for the UGT1A1*28 allele. UGT1A1 genotyping is not required for this study.
Chronic inflammatory bowel disease and/or active intestinal obstruction. Patients should not be treated until the intestinal obstruction has resolved.
Previous history of significant/severe hemorrhage, within 1 month before randomization. History of previous abdominal fistula or gastrointestinal perforation within 6 months before randomization
Known history of bleeding diathesis or coagulopathy
INR > 1.5 within 14 days prior to starting study treatment. EXEMPTION: patients on full anticoagulation must have an in-range INR (usually between 2 to 3) if INR is used for monitoring. Any anticoagulation therapy must be at stable dosing prior to enrollment.
Ongoing or anticipated treatment with potent cytochrome inhibitors CYP450 3A4 (such as ketoconazole) or inducers (such as rifampicin, carbamazepine, phenobarbital, phenytoin or St. John's wort). Irinotecan should not be delivered concurrently.
Patients with ongoing or anticipated treatment with sorivudine or its chemically related analogues, such as brivudine.
Chronic, daily treatment with high-dose aspirin (> 325 mg/day)
Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation
Receipt of any live attenuated vaccines within 4 weeks prior to first dose of study treatment
Known hypersensitivity to any of the drugs used in this study
Pregnant or lactating women
Legal incapacity or limited legal capacity
Other uncontrolled serious chronic disease or psychiatric condition that in the Investigator's opinion could affect patient safety, compliance, or follow-up in the protocol
Any contraindications to the administration of FOLFOXIRI and bevacizumab at the discretion of the investigator.

Name	Affiliation	Role
Clinical Contact	G1 Therapeutics, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
AZ Oncology Associates - HOPE		Tucson	Arizona	85711	United States
Beverly Hills Cancer Center

PubMed Identifier	Type	Citation	Retractions
39579142	Derived	Lenz HJ, Liu T, Chen EY, Horvath Z, Bondarenko I, Danielewicz I, Ghidini M, Garcia-Alfonso P, Jones R, Aapro M, Zhang Y, Wang J, Wang W, Adeleye J, Beelen A, Hubbard J. Trilaciclib prior to FOLFOXIRI/bevacizumab for patients with untreated metastatic colorectal cancer: phase 3 PRESERVE 1 trial. JNCI Cancer Spectr. 2025 Jan 3;9(1):pkae116. doi: 10.1093/jncics/pkae116.

ID	Title	Description
FG000	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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 15, 2022	Apr 29, 2024

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Duration of Severe Neutropenia (DSN)

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.

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.

Posted

Mean

Standard Deviation

days

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

ID	Title	Description
OG000	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.
OG001	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%)

Units	Counts
Participants	OG000149 OG001147

Title

Denominators

Categories

Title	Measurements
	OG0000.1± 0.84 OG0011.3± 3.14

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		<0.001	Two-sided p-value for treatment effect was generated from a nonparametric ANCOVA controlling for stratification factors of Region and Prior chemotherapy with study baseline ANC value as a covariate.	Mean Difference (Final Values)	-1.2			2-Sided	95	-1.7	-0.6					Other

Primary

Occurrence of Severe Neutropenia (SN) During Induction

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)

Posted

Number

event per 100 cycles

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

ID	Title	Description
OG000	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.
OG001	Placebo + FOLFOXIRI/Bevacizumab

Secondary

Overall Survival (OS)

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.

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

Posted

Up to 52 months

ID	Title	Description
OG000	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.
OG001	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%)

Units

Secondary

Additional Myelopreservation Measures

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)

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

Posted

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

ID	Title	Description
OG000	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.
OG001	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%)

Secondary

Red Blood Cell Lineage

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

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

Posted

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

ID	Title	Description
OG000	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.
OG001	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%)

Secondary

Platelet Lineage

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.

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

Posted

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

ID	Title	Description
OG000	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.
OG001	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%)

Secondary

Multiple Lineage

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.

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

Posted

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

ID	Title	Description
OG000	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.
OG001	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%)

Secondary

Standard of Care Dosing

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

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

Posted

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

ID	Title	Description
OG000	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.
OG001	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%)

Secondary

Healthcare Utilization

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.

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

Posted

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

ID	Title	Description
OG000	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.
OG001	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%)

Secondary

Best Overall Response (BOR)

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.

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.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	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.

Secondary

Objective Response Rate (ORR)

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.

Posted

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	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.

Secondary

Duration of Objective Response (DOR)

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.

Posted

Median

95% Confidence Interval

months

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

ID	Title	Description
OG000	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.
OG001	Placebo + FOLFOXIRI/Bevacizumab

Secondary

Progression Free Survival (PFS)

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.

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.

Posted

Mean

95% Confidence Interval

months

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

ID	Title	Description
OG000	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.
OG001	Placebo + FOLFOXIRI/Bevacizumab

Secondary

Quality of Life/ Effects on Chemotherapy-Induced Fatigue

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).

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

Posted

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

ID	Title	Description
OG000	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.
OG001	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%)

Secondary

Number of Participants With Reported Adverse Events to Measure Safety and Tolerability

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.

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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.
OG001	Placebo + FOLFOXIRI/Bevacizumab

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0012 affected160 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0015 affected160 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0015 affected160 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Cardiac failure acute	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Myocardial injury	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Abdominal adhesions	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0013 affected160 at risk
Anal fistula	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Colitis	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Constipation	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0002 affected159 at risk EG0013 affected160 at risk
Enterocutaneous fistula	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Gastrointestinal obstruction	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0011 affected160 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Ileus	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0002 affected159 at risk EG0011 affected160 at risk
Ileus paralytic	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0004 affected159 at risk EG0013 affected160 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0011 affected160 at risk
Large intestinal obstruction	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Nausea	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0011 affected160 at risk
Oesophageal rupture	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0002 affected159 at risk EG0010 affected160 at risk
Rectal perforation	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Subileus	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Vomiting	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0003 affected159 at risk EG0012 affected160 at risk
Death	General disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Device related thrombosis	General disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Pain	General disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Pyrexia	General disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0013 affected160 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Drug hypersensitivity	Immune system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Abdominal abscess	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Abscess limb	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Anal abscess	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Anorectal infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Appendicitis	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
COVID-19	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0011 affected160 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Cellulitis	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0012 affected160 at risk
Device related infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Infectious pleural effusion	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Intestinal sepsis	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Neutropenic sepsis	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Pelvic abscess	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Pneumonia	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0003 affected159 at risk EG0011 affected160 at risk
Pyelonephritis	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Sepsis	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0013 affected160 at risk
Drain site complication	Injury, poisoning and procedural complications	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Alanine aminotransferase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0012 affected160 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Blood bilirubin increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0011 affected160 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Myopathy	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Gastrointestinal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Dizziness	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Lumbar radiculopathy	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Myoclonic epilepsy	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Seizure	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Syncope	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0011 affected160 at risk
Anxiety	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Completed suicide	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Urinary retention	Renal and urinary disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0012 affected160 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0004 affected159 at risk EG0014 affected160 at risk
Pulmonary thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0002 affected159 at risk EG0010 affected160 at risk
Aortic embolus	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0010 affected160 at risk
Embolism	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Hypertension	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0001 affected159 at risk EG0011 affected160 at risk
Jugular vein thrombosis	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Superior vena cava syndrome	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Thrombosis	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0011 affected160 at risk
Venous thrombosis	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0000 affected159 at risk EG0012 affected160 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG00057 affected159 at risk EG00161 affected160 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG00027 affected159 at risk EG00135 affected160 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG00061 affected159 at risk EG00192 affected160 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (24.1)	Systematic Assessment	EG00034 affected159 at risk EG00136 affected160 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0009 affected159 at risk EG0016 affected160 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG00034 affected159 at risk EG00136 affected160 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0009 affected159 at risk EG0018 affected160 at risk
Constipation	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG00038 affected159 at risk EG00129 affected160 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG00083 affected159 at risk EG001118 affected160 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG00011 affected159 at risk EG00110 affected160 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG00010 affected159 at risk EG0016 affected160 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected159 at risk EG00111 affected160 at risk
Nausea	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG00085 affected159 at risk EG001101 affected160 at risk
Oral dysaesthesia	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected159 at risk EG0018 affected160 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG0007 affected159 at risk EG0019 affected160 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG00025 affected159 at risk EG00142 affected160 at risk
Vomiting	Gastrointestinal disorders	MedDRA (24.1)	Systematic Assessment	EG00054 affected159 at risk EG00164 affected160 at risk
Asthenia	General disorders	MedDRA (24.1)	Systematic Assessment	EG00028 affected159 at risk EG00128 affected160 at risk
Fatigue	General disorders	MedDRA (24.1)	Systematic Assessment	EG00053 affected159 at risk EG00152 affected160 at risk
Mucosal inflammation	General disorders	MedDRA (24.1)	Systematic Assessment	EG00017 affected159 at risk EG00118 affected160 at risk
Pyrexia	General disorders	MedDRA (24.1)	Systematic Assessment	EG00017 affected159 at risk EG00122 affected160 at risk
Temperature intolerance	General disorders	MedDRA (24.1)	Systematic Assessment	EG00010 affected159 at risk EG0015 affected160 at risk
COVID-19	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG00018 affected159 at risk EG00122 affected160 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG0007 affected159 at risk EG00112 affected160 at risk
Urinary tract infection	Infections and infestations	MedDRA (24.1)	Systematic Assessment	EG00011 affected159 at risk EG00110 affected160 at risk
Alanine aminotransferase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG00020 affected159 at risk EG00124 affected160 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG00020 affected159 at risk EG00124 affected160 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG00013 affected159 at risk EG00111 affected160 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0009 affected159 at risk EG0019 affected160 at risk
Neutrophil count decreased	Investigations	MedDRA (24.1)	Systematic Assessment	EG00012 affected159 at risk EG00115 affected160 at risk
Platelet count decreased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0009 affected159 at risk EG0017 affected160 at risk
Weight decreased	Investigations	MedDRA (24.1)	Systematic Assessment	EG00020 affected159 at risk EG00129 affected160 at risk
White blood cell count decreased	Investigations	MedDRA (24.1)	Systematic Assessment	EG0008 affected159 at risk EG00112 affected160 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG00036 affected159 at risk EG00139 affected160 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG00012 affected159 at risk EG00111 affected160 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG00011 affected159 at risk EG0018 affected160 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0006 affected159 at risk EG00111 affected160 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG00021 affected159 at risk EG00121 affected160 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0009 affected159 at risk EG0013 affected160 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (24.1)	Systematic Assessment	EG0006 affected159 at risk EG00112 affected160 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0009 affected159 at risk EG00113 affected160 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0009 affected159 at risk EG00111 affected160 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG00020 affected159 at risk EG0019 affected160 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0008 affected159 at risk EG0016 affected160 at risk
Dizziness	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG00013 affected159 at risk EG00119 affected160 at risk
Dysgeusia	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG00012 affected159 at risk EG00110 affected160 at risk
Headache	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG00032 affected159 at risk EG00126 affected160 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG00036 affected159 at risk EG00126 affected160 at risk
Neurotoxicity	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG00010 affected159 at risk EG00113 affected160 at risk
Paraesthesia	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG00020 affected159 at risk EG00115 affected160 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG00037 affected159 at risk EG00134 affected160 at risk
Tremor	Nervous system disorders	MedDRA (24.1)	Systematic Assessment	EG0008 affected159 at risk EG0011 affected160 at risk
Anxiety	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG00013 affected159 at risk EG00112 affected160 at risk
Insomnia	Psychiatric disorders	MedDRA (24.1)	Systematic Assessment	EG00015 affected159 at risk EG00115 affected160 at risk
Proteinuria	Renal and urinary disorders	MedDRA (24.1)	Systematic Assessment	EG00019 affected159 at risk EG00125 affected160 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG00013 affected159 at risk EG00112 affected160 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG00011 affected159 at risk EG0018 affected160 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0007 affected159 at risk EG00128 affected160 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG00014 affected159 at risk EG0019 affected160 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG00010 affected159 at risk EG0016 affected160 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected159 at risk EG0018 affected160 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (24.1)	Systematic Assessment	EG0004 affected159 at risk EG00110 affected160 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG00023 affected159 at risk EG00125 affected160 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (24.1)	Systematic Assessment	EG0004 affected159 at risk EG0018 affected160 at risk
Hypertension	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG00034 affected159 at risk EG00135 affected160 at risk
Hypotension	Vascular disorders	MedDRA (24.1)	Systematic Assessment	EG0005 affected159 at risk EG0018 affected160 at risk

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases

ID	Title	Description
BG000	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.
BG001	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%)
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	49	159	47	159	155	159
EG001	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%)	26	160	47	160	159	160