Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Gemcitabine and Carboplatin in Metastatic Triple Negative Breast Cancer (mTNBC)

Phase 2

Terminated

Conditions: Breast Cancer
Triple-Negative Breast Cancer
Triple-Negative Breast Neoplasms
Breast Neoplasm

Interventions: Drug: Gemcitabine
Drug: Trilaciclib
Drug: Carboplatin

Registration Number: NCT02978716

Lead Sponsor: G1 Therapeutics, Inc.

Brief Summary: This was a study to investigate the potential clinical benefit of trilaciclib (G1T28) in preserving the bone marrow and the immune system, and enhancing chemotherapy antitumor efficacy when administered prior to carboplatin and gemcitabine (GC therapy) for participants with metastatic triple negative breast cancer.

The study was an open-label and 102 participants were randomly assigned (1:1:1 fashion) to 1 of the 3 following treatment groups:

* Group 1: GC therapy (Days 1 and 8 of 21-day cycles) only (n=34)

* Group 2: GC therapy (Days 1 and 8) plus trilaciclib (G1T28) on Days 1 and 8 of 21-day cycles (n=33)

* Group 3: GC therapy (Days 2 and 9) plus trilaciclib (G1T28) on Days 1, 2, 8, and 9 of 21-day cycles (n=35)

The study included 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit.

Detailed Description: The posted results represent the final results of Study G1T28-04, a Phase 2 study of the safety, efficacy and pharmacokinetics of trilaciclib (G1T28) in patients with locally recurrent/metastatic triple negative breast cancer receiving gemcitabine and carboplatin chemotherapy.

The final myelopreservation efficacy results are reported from database lock 1 (\[DBL1\], data cut-off \[DCO\] date of 30 July 2018). Final anti-tumor efficacy (ORR, PFS), and final summary exposure and safety data are reported from database lock 2 (\[DBL2\], DCO 28 June 2019) which occurred to support filing of the trilaciclib New Drug Application (NDA). Final overall survival (OS) data are reported from the final database lock which occurred on 17 July 2020 (with a last patient last visit date of 28 February 2020).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 102

Inclusion Criteria

Confirmed diagnosis of hormone receptor (HR)-negative, human epidermal growth factor receptor 2 (HER2)-negative (locally recurrent or metastatic TNBC) breast cancer
Available TNBC diagnostic tumor tissue (archived tissue allowed)
Evaluable disease
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Adequate organ function
Predicted life expectancy of 3 or more months

Exclusion Criteria

More than 2 prior chemotherapy regimens for locally recurrent or metastatic TNBC. If > 12 months have elapsed between the date of last adjuvant/neoadjuvant chemotherapy administration and first documented local or distant disease recurrence the therapy will not be considered a line of therapy in the locally recurrent or metastatic TNBC setting.
CNS metastases or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
Investigational drug within 30 days of first trilaciclib (G1T28) dose
Concurrent radiotherapy, radiotherapy within 14 days of first trilaciclib (G1T28) dose
Cytotoxic chemotherapy within 3 weeks of first trilaciclib (G1T28) dose
Prior hematopoietic stem cell or bone marrow transplantation

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 2: Trilaciclib + Gemcitabine/ Carboplatin (Days 1 and 8)	Carboplatin	Participants received IV infusion of trilaciclib 240 mg/m\^2 plus GC chemotherapy (gemcitabine 1000 mg/m\^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycle. Trilaciclib was administered prior to chemotherapy.
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Gemcitabine	Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square \[mg/m\^2\] and carboplatin area under the curve \[AUC\] 2) on Days 1 and 8 of 21-day cycle. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)	Trilaciclib	Participants received IV infusion of trilaciclib 240 mg/m\^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m\^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day Cycle. Trilaciclib was administered prior to chemotherapy.
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)	Carboplatin	Participants received Intravenous (IV) infusion of standard GC chemotherapy (gemcitabine 1000 milligrams per meter square \[mg/m\^2\] and carboplatin area under the curve \[AUC\] 2) on Days 1 and 8 of 21-day cycle. The carboplatin dose was calculated using the Calvert formula, with a target AUC 2 (maximum 300 mg).
Group 2: Trilaciclib + Gemcitabine/ Carboplatin (Days 1 and 8)	Trilaciclib	Participants received IV infusion of trilaciclib 240 mg/m\^2 plus GC chemotherapy (gemcitabine 1000 mg/m\^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycle. Trilaciclib was administered prior to chemotherapy.
Group 2: Trilaciclib + Gemcitabine/ Carboplatin (Days 1 and 8)	Gemcitabine	Participants received IV infusion of trilaciclib 240 mg/m\^2 plus GC chemotherapy (gemcitabine 1000 mg/m\^2 and carboplatin AUC 2) IV infusion on Days 1 and 8 of 21-day cycle. Trilaciclib was administered prior to chemotherapy.
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)	Carboplatin	Participants received IV infusion of trilaciclib 240 mg/m\^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m\^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day Cycle. Trilaciclib was administered prior to chemotherapy.
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)	Gemcitabine	Participants received IV infusion of trilaciclib 240 mg/m\^2 on Days 1, 2, 8, and 9 plus GC chemotherapy (gemcitabine 1000 mg/m\^2 and carboplatin AUC 2) IV infusion on Day 2 and 9 of 21-day Cycle. Trilaciclib was administered prior to chemotherapy.

Primary Outcome Measures

Name	Time	Method
Duration of Severe (Grade 4) Neutropenia (DSN) During Cycle 1	From randomization to the end of Cycle 1 (Each cycle= 21 days)	DSN was defined as the number of days from the date of the first absolute neutrophil count (ANC) value of less than (\<) 0.5 × 10\^9 cells/liter (L) observed between Day 1 Cycle 1 and the end of Cycle 1 to the date of the first ANC value greater than or equal to (\>=) 0.5 × 10\^9/L that met the following: (1) occurred after the ANC value of \< 0.5 × 10\^9 cells/L and (2) no other ANC values \< 0.5 × 10\^9 cells/L occurred between this day and the end of Cycle 1. Severe neutropenia (SN) was set to zero for participants who did not experience severe (Grade 4) neutropenia in Cycle 1, including those who were randomized but never treated.
Number of Participants With Severe (Grade 4) Neutropenia (SN)	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days	Number of participants with Grade 4 SN was a binary variable. If a participants had at least 1 ANC value \< 0.5 ×10\^9/L during the treatment period, the participants was assigned as "yes" to the occurrence of SN. Otherwise, it was "no".

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Grade 3 and 4 Hematologic Toxicities	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days	Hematologic toxicities events were defined as any cycle where any hematologic lab value occurs that meets the CTCAE toxicity grade criteria for \>= Grade 3 and the value is treatment emergent. The occurrence of Grade 3 and 4 hematologic toxicities was a binary endpoint. If a participant had at least 1 cycle with at least one Grade 3 or 4 hematologic toxicities during the treatment period, the participant was assigned as Yes to the occurrence of Grade 3 and 4 hematologic toxicities; otherwise, it was No. If a participant did not have an event, the value of 0 was assigned to that participant.
Number of Participants With Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days	BOR was defined as the best response across all time points (RECIST v1.1). The best overall response was determined once all the data for the participant is known. Each participant has been assigned one of the following categories (RECIST 1.1): complete response (CR): disappearance of all target lesions; partial response (PR): \>= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; progression disease (PD): \>= 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study); stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD); NE: not evaluable and missing.
Duration of Objective Response (DOR) as Per RECIST v1.1 as Determined by Investigator	From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days	DOR is the time between first response by RECIST Version 1.1 of CR or PR and the first date that progressive disease is documented by RECIST Version 1.1, or death. Participants who do not experience PD or death was censored at the last tumor assessment date. 95% Confidence Interval (CI) was calculated using the Kaplan-Meier method.
Duration of Exposure	During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days	Duration of exposure (days) = First dose date of study drug from the last cycle - first dose date of study drug + 21.
Progression Free Survival (PFS) as Per RECIST v1.1 as Determined by Investigator	From date of randomization until the occurrence of disease progression, death due to any cause or a censoring event, assessed up to a maximum of 875 days	PFS was defined as the time (months) from date of randomization until date of documented PD or death due to any cause, whichever comes first. PD: \>= 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study). The PFS was calculated using Kaplan-Meier method.
Relative Dose Intensity of Gemcitabine and Carboplatin	During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days	Relative dose intensity was defined as 100% times the actual dose intensity divided by the planned dose intensity. The planned dose intensity was defined as the cumulative planned dose through the study divided by (number of cycles × 3 weeks). Relative dose intensity (%) was calculated as: for gemcitabine (100 \* \[Dose intensity (mg/m2/week) / (2000/3 (mg/m2/week)\]); for carboplatin (100 \* \[Dose intensity (AUC/week)/ (4/3) (AUC/week)\]) and for trilaciclib (100 \* \[Dose intensity (mg/m2/week)/ (480 /3 (mg/m2/week)\] for Group 2 and 100 \* \[Dose intensity (mg/m2/week) / (960 /3 (mg/m2/week)\] for Group 3).
Number of Cycles Participants Received Treatment in Each Treatment Arm	During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days	Participants were considered to have started a cycle if they have received at least 1 dose of any study drug.
Maximum Observed Plasma Concentration (Cmax) of Trilaciclib	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)	The observed peak plasma concentration was determined from the plasma concentration-versus time data.
Cumulative Dose of Carboplatin	During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days	Cumulative dose: Sum of the total doses by cycle (AUC) administered to a participant in the duration of exposure, i.e. total number of cycles received (in total prescribed AUC).
Terminal Elimination Half-Life (t1/2) of Free Carboplatin	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)	t1/2 was calculated as 0.693 divided by lambda z. lambda z (terminal phase rate constant) was determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve.
Clearance (CL) of of Free Carboplatin	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)	Clearance after intravenous infusion administration was calculated as: CL=Dose/AUC0-inf. AUC0-inf was calculated as: AUC0-inf=AUClast+Clast/lambdaz where Clast is the last quantifiable concentration in the terminal elimination phase.
Major Adverse Hematologic Event (MAHE) Rate	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days	MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelosuppression into a single endpoint by summing of the total number of events across a set of pre-specified components.The individual components for MAHE were all-cause hospitalizations, all-cause dose reductions, febrile neutropenia, prolonged severe neutropenia (duration \> 5 days), RBC transfusion and platelet transfusion. Event rate for MAHE was calculated as the number of events/durations of treatment period divided by 7 days/1 week.
Terminal Elimination Half-Life (t1/2) of Trilaciclib	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)	t1/2 was calculated as 0.693 divided by lambda z. lambda z (terminal phase rate constant) was determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve, the actual body exposure to drug after administration of a dose of the drug ( in mg\*h/L).
Maximum Observed Plasma Concentration (Cmax) of Gemcitabine	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)	The observed peak plasma concentration was determined from the plasma concentration-versus time data.
Number of Participants With Febrile Neutropenia (FN)	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days	The criterion for identifying FN was if the PT was "FEBRILE NEUTROPENIA" the occurrence during the treatment period was defined as a binary variable (Yes or No); Yes if total number of events \>=1 was observed, No for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant.
Number of Participants With Infection SAEs	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days	Number of participants with infection SAEs during the treatment period was defined as a binary variable (Yes or No); Yes if total number of events \>=1 was observed, No for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant. The criterion for identifying the proper infection SAE records was as follows: If the system organ class (SOC) from Medical Dictionary for Regulatory Activities (MedDRA) takes value "INFECTIONS AND INFESTATIONS," and the AE was a serious event.
Number of Participants With Red Blood Cell (RBC) Transfusions On/After Week 5 (Day 35)	From Day 35 through the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 508 days	Each RBC transfusion with a unique start date on/after 5 weeks on study during the treatment period was defined as a separate event. Occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if the total number of events \>=1 was observed and "No" for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.
Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Gemcitabine	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)	AUC0-t was calculated with the linear/log-trapezoidal method.
Volume of Distribution at Steady State (Vss) of Free Carboplatin	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)	Vss was the volume of distribution at steady state of free carboplatin was reported.
Number of Participants With Grade 3 or 4 Thrombocytopenia	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days	Hematologic toxicities events are defined as any cycle where any hematologic lab value occurs that meets the CTCAE toxicity grade criteria for \>= Grade 3 and the value is treatment emergent. The occurrence of Grade 3 and 4 thrombocytopenia was a binary endpoint. If a participant had at least 1 cycle with at least one Grade 3 or 4 thrombocytopenia during the treatment period, the participant was assigned as "Yes" to the occurrence of Grade 3 and 4 thrombocytopenia; otherwise, it was "No". If a participant did not have an event, the value of 0 was assigned to that participant.
Overall Survival (OS)	From date of randomization to date of death due to any cause, assessed up to a maximum of 1120 days	Overall survival was defined as the time (months) from date of randomization to the date of death due to any cause. Participants who do not die during the study were censored at the date last known to be alive. The OS was calculated using Kaplan-Meier method.
Cumulative Dose of Gemcitabine	During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days	Cumulative dose: Sum of the total doses by cycle administered to a participant in the duration of exposure, i.e. total number of cycles received (milligram per meter square \[mg/m\^2\]).
Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Trilaciclib	Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)	AUC0-t was calculated with the linear/log-trapezoidal method, which uses linear interpolation between data points to calculate the AUC. The linear/log-trapezoidal method will be employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method will be used for those arising from decreasing concentrations.
Number of Participants With Erythropoiesis Stimulating Agent (ESA) Administration	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days	The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if total number of events \>=1 was observed, "No" for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant. The criterion to select proper records was as follows: If the chemical subgroup from WHO-DD Version September 2017 (i.e., TEXT4 for CODE4) takes value "OTHER ANTIANEMIC PREPARATIONS", the medication was classified as ESAs.
Number of Participants With Platelet Transfusions	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days	Each platelet transfusion with a unique start date during the treatment period was defined as a separate event. The occurrence during the treatment period was defined as a binary variable (Yes or No); Yes if the total number of events \>=1 was observed and No for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.
Number of Participants With Intravenous Antibiotics Use	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days	The criteria for identifying an IV antibiotic administration event was (1) if the Therapeutic subgroup from WHO-DD version takes value "ANTIBACTERIALS FOR SYSTEMIC USE", and (2) the route of medication was "intravenous" or the route was "other" with the detailed specification as "IVPB". The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if total number of events \>=1 was observed, "No" for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant.
Dose Modifications - Number of Participants With Skipped Doses	During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days	Dose modifications was summarized for each study drug based on skipped doses not received during the treatment period. Primary reasons for skipped doses included toxicity, investigator decision and administrative reasons (e.g., holidays).
Dose Modifications - Number of Participants With Dose Reductions	During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days	Dose (mg/m2) reductions were not permitted for trilaciclib. Dose reductions for carboplatin and gemcitabine were determined by comparing the planned dose on the respective drug administration pages between the current cycle and the previous cycle.
Number of Participants With Granulocyte Colony-stimulating Factor (G-CSF) Administration	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days	The criterion for selecting proper records is as follows: If the chemical subgroup from the World Health Organization-Drug Dictionary (WHO-DD) takes value "COLONY STIMULATING FACTOR," the medication was classified as G-CSF. The occurrence during the treatment period was defined as a binary variable (Yes or No); "Yes" if the total number of events \>=1 was observed and "No" for other scenarios. If a participant did not have an event, the value of 0 will be assigned to that participant.
All-cause Dose Reductions, Event Rate (Per Cycle)	During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days	Dose reductions were not permitted for trilaciclib. Dose reductions for gemcitabine or carboplatin were collected on the dosing page. No more than 3 dose modifications for toxicity in total were allowed for any participant. All dose reductions were counted as a separate event. Discontinuations of an individual component of the chemotherapy regimen were counted as a dose reduction If the participant continued the other chemotherapy drug as a monotherapy. Event rate was calculated as the total number of cycles with an event divided by the total number of cycles.
Dose Modifications: Number of Participants With Cycle Delays	During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days	Dose modifications was summarized for each study drug based on number of cycles received during the treatment period. If the participant was unable to start a new cycle at that next visit, then the cycle is delayed, the reason entered, and the question was asked again at the next visit until the participant either starts a new cycle or discontinues treatment.
Dose Modifications: Number of Participants With Any Dose Interruptions	During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days	Dose interruptions was defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.

Trial Locations

Locations (51): Florida Cancer Specialists
🇺🇸
Fort Myers, Florida, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸
Dallas, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸
Fairfax, Virginia, United States
Virginia Oncology Associates
🇺🇸
Virginia Beach, Virginia, United States
Florida Cancer Specialists - East (FCS East)
🇺🇸
West Palm Beach, Florida, United States
University of Maryland Greenebaum Comprehensive Cancer Center
🇺🇸
Baltimore, Maryland, United States
Community Health Network
🇺🇸
Indianapolis, Indiana, United States
Sharp Clinical Oncology
🇺🇸
San Diego, California, United States
Comprehensive Cancer Centers of Nevada
🇺🇸
Las Vegas, Nevada, United States
University Multiprofile Hospital for Active Treatment
🇧🇬
Sofia, Bulgaria
General Hospital Varaždin
🇭🇷
Varazdin, Croatia
University Hospital Centre "Sestre milosrdnice"
🇭🇷
Zagreb, Croatia
Multiprofile Hospital for Active Treatment
🇧🇬
Varna, Bulgaria
MHAT for Womens Health - Nadezhda OOD
🇧🇬
Sofia, Bulgaria
University Hospital Centre Osijek
🇭🇷
Osijek, Croatia
Rocky Mountain Cancer Centers
🇺🇸
Lakewood, Colorado, United States
Special Hospital for Internal Diseases , Oncomed
🇷🇸
Belgrade, Serbia
Mammacentrum, Sv.Agáty
🇸🇰
Banská Bystrica, Slovakia
Saint Alphonsus Regional Medical Center
🇺🇸
Boise, Idaho, United States
Clinical Hospital Centre Bezanijska Kosa, Oncology Clinic
🇷🇸
Belgrade, Serbia
Clinical Centre Nis, Clinic of Oncology
🇷🇸
Nis, Serbia
Tennessee Oncology
🇺🇸
Nashville, Tennessee, United States
Texas Oncology-San Antonio Northeast
🇺🇸
San Antonio, Texas, United States
Antwerp University Hospital (UZA)
🇧🇪
Edegem, Belgium
Arizona Oncology Associates, PC - HOPE
🇺🇸
Tucson, Arizona, United States
Disney Family Cancer Center
🇺🇸
Burbank, California, United States
Innovative Clinical Research Institute
🇺🇸
Whittier, California, United States
Memorial UC Health
🇺🇸
Colorado Springs, Colorado, United States
Florida Cancer Specialists - North (FCS North)
🇺🇸
Saint Petersburg, Florida, United States
Florida Cancer Research Institute, LLC.
🇺🇸
Plantation, Florida, United States
Illinois Cancer Specialists
🇺🇸
Arlington Heights, Illinois, United States
The University of Maryland St. Joseph Medical Center
🇺🇸
Towson, Maryland, United States
Levine Cancer Center
🇺🇸
Charlotte, North Carolina, United States
Texas Oncology, P.A.
🇺🇸
Tyler, Texas, United States
Texas Oncology-Dallas Presbyterian Hospital
🇺🇸
Austin, Texas, United States
The Center for Cancer and Blood Disorders
🇺🇸
Fort Worth, Texas, United States
Texas Oncology-El Paso Cancer Treatment Center Grandview
🇺🇸
El Paso, Texas, United States
Tyler Hematology-Oncology, PA
🇺🇸
Tyler, Texas, United States
University of Virginia
🇺🇸
Charlottesville, Virginia, United States
Northwest Medical Specialties, PLLC
🇺🇸
Tacoma, Washington, United States
Special Hospital For Active Treatment In Oncology
🇧🇬
Sofia, Bulgaria
University Hospital Centre Zagreb
🇭🇷
Zagreb, Croatia
Center for Oncology and Radiotherapy, Clinical Centre
🇷🇸
Kragujevac, Serbia
University Clinic of Radiotherapy and Oncology
🇲🇰
Skopje, North Macedonia
Clinical Hospital Dr. Trifun Panovski
🇲🇰
Bitola, North Macedonia
Oncology Institute of Vojvodina, Clinic for Internal Oncology
🇷🇸
Sremska Kamenica, Serbia
Cancer Institute VOU, Rastislavova
🇸🇰
Košice, Slovakia
University Medical Centre Maribor
🇸🇮
Maribor, Slovenia
Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Saint Luke's Cancer Institute
🇺🇸
Kansas City, Missouri, United States
Forsyth Memorial Hospital, Novant Health Oncology Specialists
🇺🇸
Winston-Salem, North Carolina, United States