A Phase 2, Open-Label, Single-Arm Study of Single-Dose Lead-In and Neoadjuvant Trilaciclib and Chemotherapy in Patients With Early-Stage Triple Negative Breast Cancer (TNBC)

G1 Therapeutics, Inc.7 sites in 1 country24 target enrollmentMarch 3, 2022

ConditionsTriple Negative Breast Cancer Breast Cancer

InterventionsTrilaciclib Cylophosphamide Doxorubicin Paclitaxel Carboplatin (Investigator discretion)Pembrolizumab (Investigator discretion)

DrugsTrilaciclib Cylophosphamide Doxorubicin Paclitaxel Carboplatin (Investigator discretion)

Overview

Phase: Phase 2
Intervention: Trilaciclib
Conditions: Triple Negative Breast Cancer
Sponsor: G1 Therapeutics, Inc.
Enrollment: 24
Locations: 7
Primary Endpoint: Immune-based Mechanism of Action
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate the mechanism of action, as well as the safety and efficacy of trilaciclib in combination with standard of care treatment in the neoadjuvant setting of early-stage triple negative breast cancer (TNBC).

This study will have four phases: 1) Screening Phase, 2) Trilaciclib Lead-In Phase, 3) Treatment Phase, and 4) Surgery and Follow-Up Phase. After a screening phase of up to 21 day, each participant will receive trilaciclib single-dose monotherapy during the lead-in phase, followed by a tumor biopsy. During the treatment phase, each participant will receive trilaciclib with standard of care chemotherapy. Immunotherapy may be included during the treatment phase, per standard of care. 3-5 weeks following conclusion of the treatment phase, each participant will undergo definitive surgery. A 30-day Safety Follow-up Visit will occur 30 days after the last dose of trilaciclib and an End of Study Visit will occur within 14 days after definitive surgery.

Registry

clinicaltrials.gov

Start Date

March 3, 2022

End Date

March 13, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

G1 Therapeutics, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Suitability of therapy and patient intends to undergo curative surgery
•Documented diagnosis of estrogen receptor (ER)-negative and progesterone receptor (PR)-negative tumor
•Primary tumor ≥ 1.5 cm with any nodal status
•Provide archival tissue for the baseline tissue sample
•ECOG performance status of 0 or 1
•Demonstrates adequate organ function
•Research tumor biopsies including at least one on-treatment biopsy (and additional biopsy at baseline, if required)
•Participants of child bearing potential must be willing to use 2 forms of contraception during the study and for 6 months following study treatment

Exclusion Criteria

•Prior systemic therapies or radiation for current breast cancer
•History of invasive malignancy ≤3 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
•History of breast cancer including ipsilateral ductal carcinoma in situ (DCIS) treated with radiotherapy at any time
•Previous exposure to doxorubicin of more than 200 mg/m2 (as lifetime exposure to doxorubicin is not to exceed 450 mg/m2)
•For patients who will receive pembrolizumab:
•History of active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is not considered a form of systemic treatment
•Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drugs
•History of (non-infectious) pneumonitis that required steroids or current pneumonitis
•Known history of active tuberculosis (Bacillus Tuberculosis)
•History of severe hepatic impairment

Arms & Interventions

Trilaciclib plus chemotherapy

Trilaciclib lead-in, followed by trilaciclib plus anthracycline/cyclophosphamide, then trilaciclib plus taxane chemotherapy: * Lead-in trilaciclib (240mg/m2) single dose monotherapy * Trilaciclib (240mg/m2) + doxorubicin (60 mg/m2) + cyclophosphamide (600 mg/m2) + pembrolizumab (per Investigator discretion; 400mg) * Trilaciclib (240mg/m2) + paclitaxel (80 mg/m2) + carboplatin (per Investigator discretion; AUC 1.5)

Intervention: Trilaciclib

Trilaciclib plus chemotherapy

Intervention: Cylophosphamide

Trilaciclib plus chemotherapy

Intervention: Doxorubicin

Trilaciclib plus chemotherapy

Intervention: Paclitaxel

Trilaciclib plus chemotherapy

Intervention: Carboplatin (Investigator discretion)

Trilaciclib plus chemotherapy

Intervention: Pembrolizumab (Investigator discretion)

Outcomes

Primary Outcomes

Immune-based Mechanism of Action

Time Frame: Up to 8 days after lead-in trilaciclib dose

Evaluated 7 days after a single-dose of trilaciclib, measured by the change in CD8+ T cells/regulatory T cells (Treg) ratio in tumor tissue; post-trilaciclib ratio minus pre-trilaciclib ratio. Research shows a correlation between immune cells, (tumor-infiltrating lymphocytes - TILs), and favorable outcomes. Both the presence of effector CD8+ T cells and the ratio of effector CD8+ T cells to immune-suppressive regulatory T cells (Treg) correlate with improved outcome and long-term survival in solid cancers. Therefore, the higher the ratio of CD8+ T cells/Tregs, the better the predicted outcome for a patient. This outcome measure is completed by looking at tumor tissue under a microscope.