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Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Gemcitabine and Carboplatin for Metastatic Triple-Negative Breast Cancer (TNBC)

Phase 3
Completed
Conditions
TNBC - Triple-Negative Breast Cancer
Breast Cancer
Interventions
Registration Number
NCT04799249
Lead Sponsor
G1 Therapeutics, Inc.
Brief Summary

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of trilaciclib versus placebo administered prior to gemcitabine and carboplatin in patients receiving first- or second-line treatment for locally advanced unresectable/metastatic TNBC.

Detailed Description

This study will have two separate cohorts (Cohort 1 and Cohort 2). Both cohorts will follow the same general study conduct/design with similar primary and key secondary endpoints and identical treatment arms.

* Cohort 1 will evaluate patients receiving first-line therapy, regardless of programmed death-ligand 1 (PD-L1) status, who are programmed cell death protein 1 (PD-1)/PD-L1 inhibitor therapy naïve.

* Cohort 2 will evaluate PD-L1 positive patients receiving second-line therapy following prior PD-1/PD-L1 inhibitor therapy in the locally advanced unresectable/metastatic setting.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
194
Inclusion Criteria
  1. Age >/= 18 years of age with evaluable locally advanced unresectable or metastatic TNBC.

  2. Documentation of triple negative breast cancer (estrogen and progesterone receptor <1% and HER2-negative)

  3. Prior systemic therapies (Cohort 1 only):

    1. No prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, targeted therapy, immunotherapy, or investigational agents.
    2. Prior PD-1/PD-L1 inhibitor treatment is not permitted in any setting, including in the neoadjuvant setting.
    3. Time between completion of last treatment with curative intent and first metastatic recurrence must be ≥ 6 months.
  4. Prior systemic therapies (Cohort 2 only):

    1. Documentation of PD-L1 positive status
    2. Treated with a PD-1/PD-L1 inhibitor for a minimum duration of 4 months in the locally advanced unresectable/metastatic setting and as the most recent therapy.
  5. Radiation therapy for metastatic disease is permitted. There is no required minimum washout period for radiation therapy. Patients should be recovered from the effects of radiation.

  6. Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor.

  7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

  8. Adequate organ function as demonstrated by normal laboratory values

Exclusion Criteria
  1. Prior treatment with gemcitabine in any setting.

  2. Prior treatment with carboplatin in the locally advanced unresectable/metastatic setting.

    Prior carboplatin in the (neo)adjuvant/curative setting is permitted as long as it was completed ≥ 6 months prior to the first metastatic recurrence.

  3. Presence of central nervous system (CNS) metastases and/or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.

  4. Receipt of any cytotoxic chemotherapy within 14 days prior to the first dose of study drugs.

  5. QTcF interval >480 msec at Screening (confirmed in triplicate). For patients with ventricular pacemakers, QTcF >500 msec.

  6. Known hypersensitivity to carboplatin or other platinum-containing compounds, or mannitol

  7. Pregnant or lactating women

  8. Prior hematopoietic stem cell or bone marrow transplantation

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo + gemcitabine + carboplatinPlaceboThe subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.
Trilaciclib + gemcitabine + carboplatinGemcitabineTrilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2)
Trilaciclib + gemcitabine + carboplatinTrilaciclibTrilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2)
Trilaciclib + gemcitabine + carboplatinCarboplatinTrilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2)
Placebo + gemcitabine + carboplatinCarboplatinThe subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.
Placebo + gemcitabine + carboplatinGemcitabineThe subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.
Primary Outcome Measures
NameTimeMethod
Effect on Overall Survival (OS)Cohort 2: From date of randomization up to 28 months

(Cohort 2): To evaluate the effect of trilaciclib on OS compared with placebo in patients receiving gemcitabine and carboplatin as second-line therapy after treatment with a PD-1/PD-L1 inhibitor in the locally advanced unresectable/metastatic setting

Secondary Outcome Measures
NameTimeMethod
Myeloprotective EffectsCycle 1 Day 1 (each cycle is 21 days) up to 14 months

Occurrence of cytopenias, febrile neutropenia, hospitalization due to chemotherapy-induced myelosuppression, RBC and platelet transfusions, growth factor administration, and dose reductions and delays

Progression Free SurvivalFrom date of randomization up to 14 months)

To evaluate the effect of trilaciclib on progression-free survival (PFS) compared with placebo in patients receiving gemcitabine and carboplatin.

Quality of life/Effects On Chemotherapy-Induced FatigueCycle 1 Day 1 (each cycle is 21 days) up to 14 months

To assess the effect of trilaciclib on patients' quality of life as measured by time to first confirmed deterioration of fatigue compared with placebo in patients receiving gemcitabine and carboplatin

Trial Locations

Locations (71)

Banner M.D. Anderson Cancer Center

🇺🇸

Gilbert, Arizona, United States

Washington Cancer Institute at MedStar Washington Hospital Center - Oncology Research

🇺🇸

Washington, District of Columbia, United States

Florida Cancer Specialists - North (SCRI)

🇺🇸

Saint Petersburg, Florida, United States

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

Maryland Oncology Hematology, P.A.

🇺🇸

Clinton, Maryland, United States

Saint Luke's Cancer Specialists

🇺🇸

Kansas City, Missouri, United States

Comprehensive Cancer Genetics of Nevada

🇺🇸

Las Vegas, Nevada, United States

Duke Cancer Center

🇺🇸

Durham, North Carolina, United States

UPC Pinnacle Health Cancer Institute

🇺🇸

Pittsburgh, Pennsylvania, United States

Tennessee Oncology Chattanooga

🇺🇸

Chattanooga, Tennessee, United States

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Banner M.D. Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States

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