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

Phase 2 Study of the Safety, Efficacy, and Pharmacokinetics of G1T28 in Patients With Metastatic Triple Negative Breast Cancer Receiving Gemcitabine and Carboplatin Chemotherapy

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Breast Neoplasm; Triple-Negative Breast Cancer; Triple-Negative Breast Neoplasms
• Intervention / Treatment: Drug: Gemcitabine; Drug: Carboplatin; Drug: Trilaciclib

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).

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 10 2650
    • Antwerp University Hospital (UZA)
• Bulgaria
  • Sofia, Bulgaria, 1330
    • MHAT for Womens Health - Nadezhda OOD
  • Sofia, Bulgaria, 1756
    • Special Hospital For Active Treatment In Oncology
  • Sofia, Bulgaria, 1000
    • University Multiprofile Hospital for Active Treatment
  • Varna, Bulgaria, 9000
    • Multiprofile hospital for active treatment
• Croatia
  • Osijek, Croatia, 31000
    • University Hospital Centre Osijek
  • Varazdin, Croatia, 42000
    • General Hospital Varazdin
  • Zagreb, Croatia, 10000
    • University Hospital Centre Zagreb
  • Zagreb, Croatia, 10000
    • University Hospital Centre "Sestre Milosrdnice"
• North Macedonia
  • Bitola, North Macedonia, 7000
    • Clinical Hospital Dr. Trifun Panovski
  • Skopje, North Macedonia, 1000
    • University Clinic of Radiotherapy and Oncology
• Serbia
  • Belgrade, Serbia, 11000
    • Special Hospital for Internal Diseases , Oncomed
  • Belgrade, Serbia, 11070
    • Clinical Hospital Centre Bezanijska Kosa, Oncology Clinic
  • Kragujevac, Serbia, 34000
    • Center for Oncology and Radiotherapy, Clinical Centre
  • Nis, Serbia, 18000
    • Clinical Centre Nis, Clinic of Oncology
  • Sremska Kamenica, Serbia, 21204
    • Oncology Institute of Vojvodina, Clinic for Internal Oncology
• Slovakia
  • Banská Bystrica, Slovakia, 974 01
    • Mammacentrum, Sv.Agáty
  • Košice, Slovakia, 040 01
    • Cancer Institute VOU, Rastislavova
• Slovenia
  • Maribor, Slovenia, 2000
    • University Medical Centre Maribor
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Arizona Oncology Associates, PC - HOPE
  • California
    • Burbank, California, United States, 91505
      • Disney Family Cancer Center
    • San Diego, California, United States, 92123
      • Sharp Clinical Oncology
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Memorial UC Health
    • Lakewood, Colorado, United States, 80228
      • Rocky Mountain Cancer Centers
  • Florida
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists
    • Plantation, Florida, United States, 33324
      • Florida Cancer Research Institute, LLC.
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists - North (FCS North)
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists - East (FCS East)
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Regional Medical Center
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Illinois Cancer Specialists
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Community Health Network
  • Maryland
    • Baltimore, Maryland, United States, 21201-1544
      • University of Maryland Greenebaum Comprehensive Cancer Center
    • Towson, Maryland, United States, 21204
      • The University of Maryland St. Joseph Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64113
      • Saint Luke's Cancer Institute
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Center
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Memorial Hospital, Novant Health Oncology Specialists
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Austin, Texas, United States, 75231
      • Texas Oncology-Dallas Presbyterian Hospital
    • Austin, Texas, United States, 78745
      • Texas Oncology, P.A.
    • Bedford, Texas, United States, 76022
      • Texas Oncology, P.A.
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • El Paso, Texas, United States, 79902
      • Texas Oncology-El Paso Cancer Treatment Center Grandview
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders
    • San Antonio, Texas, United States, 78217
      • Texas Oncology-San Antonio Northeast
    • Tyler, Texas, United States, 75702
      • Texas Oncology, P.A.
    • Tyler, Texas, United States, 75701
      • Tyler Hematology-Oncology, PA
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
    • Virginia Beach, Virginia, United States, 23456
      • Virginia Oncology Associates
  • Washington
    • Tacoma, Washington, United States, 98405
      • NorthWest Medical Specialties, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Gemcitabine/Carboplatin (Days 1 and 8); 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).	Drug: Gemcitabine; Gemcitabine; Drug: Carboplatin; Carboplatin
Experimental: Group 2: Trilaciclib + Gemcitabine/ Carboplatin (Days 1 and 8); 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.	Drug: Gemcitabine; Gemcitabine; Drug: Carboplatin; Carboplatin; Drug: Trilaciclib; G1T28; Other Names: G1T28; CDK 4/6 Inhibitor
Experimental: Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9); 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.	Drug: Gemcitabine; Gemcitabine; Drug: Carboplatin; Carboplatin; Drug: Trilaciclib; G1T28; Other Names: G1T28; CDK 4/6 Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Severe (Grade 4) Neutropenia (DSN) During Cycle 1	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.	From randomization to the end of Cycle 1 (Each cycle= 21 days)
Number of Participants With Severe (Grade 4) Neutropenia (SN)	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".	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	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.	From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days
Duration of Objective Response (DOR) as Per RECIST v1.1 as Determined by Investigator	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.	From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days
Overall Survival (OS)	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.	From date of randomization to date of death due to any cause, assessed up to a maximum of 1120 days
Progression Free Survival (PFS) as Per RECIST v1.1 as Determined by Investigator	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.	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
Relative Dose Intensity of Gemcitabine and Carboplatin	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).	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	Duration of exposure (days) = First dose date of study drug from the last cycle - first dose date of study drug + 21.	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
Number of Cycles Participants Received Treatment in Each Treatment Arm	Participants were considered to have started a cycle if they have received at least 1 dose of any study drug.	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 of Gemcitabine	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]).	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 of Carboplatin	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).	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
Maximum Observed Plasma Concentration (Cmax) of Trilaciclib	The observed peak plasma concentration was determined from the plasma concentration-versus time data.	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)
Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Trilaciclib	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.	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)
Terminal Elimination Half-Life (t1/2) of Trilaciclib	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).	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)
Maximum Observed Plasma Concentration (Cmax) of Gemcitabine	The observed peak plasma concentration was determined from the plasma concentration-versus time data.	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)
Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Gemcitabine	AUC0-t was calculated with the linear/log-trapezoidal method.	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)
Terminal Elimination Half-Life (t1/2) of Free Carboplatin	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.	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 (CL) of of Free Carboplatin	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.	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)
Volume of Distribution at Steady State (Vss) of Free Carboplatin	Vss was the volume of distribution at steady state of free carboplatin was reported.	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)
Number of Participants With Grade 3 and 4 Hematologic Toxicities	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.	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 3 or 4 Thrombocytopenia	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.	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
Major Adverse Hematologic Event (MAHE) Rate	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.	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 Febrile Neutropenia (FN)	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.	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	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.	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 Red Blood Cell (RBC) Transfusions On/After Week 5 (Day 35)	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.	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
Number of Participants With Platelet Transfusions	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.	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 Granulocyte Colony-stimulating Factor (G-CSF) Administration	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.	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 Erythropoiesis Stimulating Agent (ESA) Administration	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.	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 Intravenous Antibiotics Use	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.	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
All-cause Dose Reductions, Event Rate (Per Cycle)	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.	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 Modifications: Number of Participants With Cycle Delays	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.	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 - Number of Participants With Skipped Doses	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).	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: Number of Participants With Any Dose Interruptions	Dose interruptions was defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.	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 - Number of Participants With Dose Reductions	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.	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	An Adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product that did not necessarily have a causal relationship with this treatment. Any AE that started on or after the first dose of study drugs was included as a TEAE. A Serious AE was defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) and regardless of causality that met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. TEAEs included serious and non-serious TEAEs.	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 1116 days

Collaborators and Investigators

• Sponsor: G1 Therapeutics, Inc.

Publications and helpful links

General Publications

• Tan AR, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, Vojnovic Z, Vasev N, Ma L, Richards DA, Wilks ST, Milenkovic D, Yang Z, Antal JM, Morris SR, O'Shaughnessy J. Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 2019 Nov;20(11):1587-1601. doi: 10.1016/S1470-2045(19)30616-3. Epub 2019 Sep 28.
• Tan AR, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, Vojnovic Z, Vasev N, Ma L, Richards DA, Wilks ST, Milenkovic D, Xiao J, Sorrentino J, Horton J, O'Shaughnessy J. Trilaciclib Prior to Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer: Final Efficacy and Subgroup Analysis from a Randomized Phase II Study. Clin Cancer Res. 2022 Feb 15;28(4):629-636. doi: 10.1158/1078-0432.CCR-21-2272.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2017
• Primary Completion (Actual): June 28, 2019
• Study Completion (Actual): February 28, 2020

Study Registration Dates

• First Submitted: November 18, 2016
• First Submitted That Met QC Criteria: November 28, 2016
• First Posted (Estimate): December 1, 2016

Study Record Updates

• Last Update Posted (Actual): March 23, 2022
• Last Update Submitted That Met QC Criteria: February 24, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Breast Cancer; Metastatic; Triple Negative Breast Cancer; CDK 4/6 Inhibitor
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Site; Breast Diseases; Neoplasms; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Carboplatin
• Other Study ID Numbers: G1T28-04; 2016-004466-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No