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

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06027268

Collaborator

Merck Sharp & Dohme LLC (Industry), G1 Therapeutics, Inc. (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Metastatic Triple-Negative Breast Cancer	Drug: Trilaciclib Drug: Pembrolizumab Drug: Gemcitabine Drug: Carboplatin	Phase 2

Detailed Description

This is an open label, single-arm, phase II trial designed to evaluate the efficacy of trilaciclib, pembrolizumab, gemcitabine and carboplatin in participants with locally advanced unresectable or metastatic triple-negative breast cancer. Pembrolizumab will be given for a maximum of 2 years. Eligible participants will receive the study treatment until disease progression, unacceptable toxicity, or withdrawal for any reason. A tumor biopsy will be collected from participants in which it can be safely obtained before the first dose of treatment, prior to Cycle 3 Day 1, and at the time of disease progression (optional). Blood specimens for correlative studies will be collected pre-treatment Cycle 1 Day 1, prior to treatment Cycle 2 Day 1, prior to treatment Cycle 3 Day 1, 3 months after the start of study treatment, and 6 months after the start of study treatment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

ToPCourT: A Phase II Trial of Trilaciclib, Pembrolizumab, Gemcitabine and Carboplatin in Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (TNBC)

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2026

Anticipated Study Completion Date :

Mar 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trilaciclib, Pembrolizumab, Gemcitabine, and Carboplatin 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 IV infusion Day 1 and Day 8 every 21 days, at dose of 240 mg/m2 Other Names: COSELA Drug: Pembrolizumab IV infusion Day 1 every 21 days, at dose of 200 mg Other Names: KEYTRUDA Drug: Gemcitabine IV infusion Day 1 and Day 8 every 21 days, at dose 1000 mg/m2 Other Names: Gemzar Drug: Carboplatin IV infusion Day 1 and Day 8 every 21 days, at dose area under curve (AUC) 2 (maximum of 300 mg)

Arm

Intervention/Treatment

Experimental: Trilaciclib, Pembrolizumab, Gemcitabine, and Carboplatin

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

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

Other Names:

COSELA

Drug: Pembrolizumab

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

Other Names:

KEYTRUDA

Drug: Gemcitabine

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

Other Names:

Gemzar

Drug: Carboplatin

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

Outcome Measures

Primary Outcome Measures

Objective Response [6 months (initiation of protocol directed therapy until either a partial response is achieved or treatment discontinuation)]
Objective according to RECIST v1.1 criteria

Secondary Outcome Measures

Progression-free survival [1 year (initiation of protocol directed therapy until documented disease progression, death, or end of follow-up period)]
Time to disease progression per RECIST v1.1 criteria or death
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)]
Duration of response will be calculated only for subjects who achieve an objective response according to RECIST v1.1 criteria (a CR or PR). Disease progression will be objectively determined as per RECIST 1.1 criteria or progression can be subjective as determined by the Investigator.
Overall survival [1 year (initiation of protocol directed therapy until documented death, or end of follow-up period])]
Time to date of death due to any cause while on study

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 IHC 0 or 1+ or fluorescence in-situ hybridization (FISH) HER2: chromosome enumeration probe 17 (CEP) ratio <2.0 with an average copy number of <4 signals/nucleus per 2018 American Society of Clinical Oncology and the College of American Pathologists (ASCO CAP) criteria. 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

Exclusion Criteria:

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
Prior hematopoietic stem cell or bone marrow transplant or allogenic tissue/solid organ transplant
Has a known history of Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive).
Has known active hepatitis C (e.g., hepatitis C virus (HCV) ribonucleic acid (RNA) [qualitative] is detected).
Receipt of a live, attenuated vaccine within 30 days prior to day 1 of study treatment or anticipation that such a live, attenuated vaccine will be required during the study treatment period. Administration of killed vaccines is allowed. Exception: Monkeypox vaccine may be given if there are at least 3 days between the vaccine and initiation of study treatment.