Phase II Trial of Trilaciclib, Pembrolizumab, Gemcitabine and Carboplatin in Metastatic Triple-Negative Breast Cancer

NCT06027268 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB00095334LCI-BRE-MTN-TPGC-001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this phase II study is to test the combination of trilaciclib, pembrolizumab, gemcitabine, and carboplatin in locally advanced unresectable or metastatic triple-negative breast cancer. The main questions it aims to answer are:

• to evaluate the anti-cancer efficacy (assess how well it works)
• to evaluate the safety and tolerability (how well the body can handle the treatment) of this combination of anti-cancer therapy

Conditions

Metastatic Triple-Negative Breast Cancer

Keywords

Breast-Female; Breast-Male; Triple-Negative Breast Cancer; Metastatic; Locally advanced unresectable

Outcome Measures

Primary Outcomes (1)

• Objective Response

  Objective according to RECIST v1.1 criteria

  6 months (initiation of protocol directed therapy until either a partial response is achieved or treatment discontinuation)

Secondary Outcomes (3)

• Progression-free survival

  1 year (initiation of protocol directed therapy until documented disease progression, death, or end of follow-up period)

• Duration of response

  1 year (time from first disease assessment that shows a PR or complete response (CR) until documented disease progression, death, or end of follow-up period)

• Overall survival

  1 year (initiation of protocol directed therapy until documented death, or end of follow-up period])

Other Outcomes (6)

• Adverse Events

  30 days (initiation of protocol directed therapy until 30 days after last dose, or removal from study while on treatment)

• Serious Adverse Events

  30 days (initiation of protocol directed therapy until 30 days after last dose, or removal from study while on treatment)

• Adverse Event Related Dose Delays

  30 days (initiation of protocol directed therapy until 30 days after last dose, or removal from study while on treatment)

Study Arms (1)

Trilaciclib, Pembrolizumab, Gemcitabine, and Carboplatin

EXPERIMENTAL

Trilaciclib is an agent that helps protect the bone marrow from the side effects of chemotherapy. It is given as an intravenous (IV) infusion over 30 minutes prior to gemcitabine and carboplatin. Gemcitabine is given IV over 30 minutes. Carboplatin is given over 30 minutes. Trilaciclib, gemcitabine and carboplatin are given on Days 1 and 8 every 21 days. Pembrolizumab is given IV over 30 minutes on Day 1 every 21 days.

Drug: Trilaciclib; Drug: Pembrolizumab; Drug: Gemcitabine; Drug: Carboplatin

Interventions

Trilaciclib DRUG

IV infusion Day 1 and Day 8 every 21 days, at dose of 240 mg/m2

Also known as: COSELA

Trilaciclib, Pembrolizumab, Gemcitabine, and Carboplatin

Pembrolizumab DRUG

IV infusion Day 1 every 21 days, at dose of 200 mg

Also known as: KEYTRUDA

Trilaciclib, Pembrolizumab, Gemcitabine, and Carboplatin

Gemcitabine DRUG

IV infusion Day 1 and Day 8 every 21 days, at dose 1000 mg/m2

Also known as: Gemzar

Trilaciclib, Pembrolizumab, Gemcitabine, and Carboplatin

Carboplatin DRUG

IV infusion Day 1 and Day 8 every 21 days, at dose area under curve (AUC) 2 (maximum of 300 mg)

Trilaciclib, Pembrolizumab, Gemcitabine, and Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information signed by the patient
• Male or female with locally advanced unresectable or metastatic TNBC
• Age ≥ 18 years at the time of consent
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 evaluated within 28 days prior to day 1 of study treatment
• Histological or cytological confirmation of estrogen negative and progesterone negative tumor, defined as \< 10% staining on immunohistochemistry (IHC) and human epidermal growth factor receptor type 2 (HER2)-negative, defined as HER 2 IHC 0 or 1+ or IHC 2+ with no amplification. Patients may be enrolled regardless of their PD-L1 (programmed death ligand-1) status.
• Measurable disease according to response evaluation criteria in solid tumors
• Demonstrate adequate organ function
• Female patients: All females of childbearing potential must have a negative serum β-human chorionic gonadotropin (hCG) test result at Screening and negative serum or urine pregnancy test results within 72 hours prior to day 1 of study treatment.
• Subject agrees to use contraception
• As determined by the enrolling physician, the ability of the subject to understand and comply with study procedures for the entire length of the study
• Tumor tissue: Willing to provide tumor tissue for research purposes
• Subject has a life expectancy of ≥ 12 weeks

You may not qualify if:

• More than 3 prior lines of chemotherapy for locally advanced unresectable or triple-negative metastatic disease
• Prior therapy with the concurrent combination of gemcitabine and carboplatin in the metastatic setting
• Active, symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis or CNS metastases that are progressing on screening magnetic resonance imaging (MRI) brain.
• Prior systemic anti-cancer therapy within 3 weeks, prior stereotactic radiotherapy within 1 week, and radiation within 2 weeks of day 1 of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation to non-CNS disease.
• Major surgery, defined by the investigator's discretion, within 3 weeks of day 1 of study treatment
• Not recovered from all reversible acute toxic effects of prior therapy, including non-hematologic toxicities related to prior systemic therapy to ≤ Grade 1. Participants with less than Grade 2 neuropathy or alopecia of any grade are an exception
• Active infection requiring systemic therapy
• Pregnant or breastfeeding
• Participants previously diagnosed with an additional malignancy must be disease-free for at least five years prior to enrollment. Exceptions include basal cell or squamous cell skin cancer and in situ cervical or bladder cancer.
• Treatment with any investigational drug within 30 days or at least 5 half-lives, whichever is longer, prior to day 1 of study treatment
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled symptomatic congestive heart failure (Class III or IV as defined by the New York Heart Association (NYHA) functional classification system), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations/substance abuse that would limit compliance with study requirements as determined by the investigator
• Known history of stroke or cerebrovascular event within 6 months prior to the day 1 of study treatment
• Known hypersensitivity to carboplatin or other platinum-containing compounds, gemcitabine, mannitol, or pembrolizumab
• History of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids or current ILD/ pneumonitis.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) prior to day 1 of study treatment. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Merck Sharp & Dohme LLC: collaborator
• G1 Therapeutics, Inc.: collaborator

Study Sites (1)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Related Publications (4)

• 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.

  PMID: 31575503 BACKGROUND

• 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.

  PMID: 34887261 BACKGROUND

• Tan AR, O'Shaughnessy J, Cao S, Ahn S, Yi JS. Investigating potential immune mechanisms of trilaciclib administered prior to chemotherapy in patients with metastatic triple-negative breast cancer. Breast Cancer Res Treat. 2023 Sep;201(2):307-316. doi: 10.1007/s10549-023-07009-8. Epub 2023 Jul 7.

  PMID: 37418031 BACKGROUND

• Sears-Smith MB, Matusz-Fisher A, Symanowski JT, Tan AR. ToPCourT protocol: a phase II trial of Trilaciclib, Pembrolizumab, gemcitabine, and Carboplatin in locally advanced/unresectable or metastatic Triple-negative breast cancer. Future Oncol. 2026 Apr;22(8):911-917. doi: 10.1080/14796694.2026.2639737. Epub 2026 Mar 11.

  PMID: 41810725 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Neoplasm Metastasis

Interventions

trilaciclib; pembrolizumab; Gemcitabine; Carboplatin

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Antoinette Tan, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2023
• First Posted: September 7, 2023
• Study Start: January 10, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)