Trilaciclib, a CDK4/6 Inhibitor, in Patients With Early-Stage Triple Negative Breast Cancer

Phase 2

Completed

Conditions: Breast Cancer
Triple Negative Breast Cancer

Interventions: Drug: Trilaciclib
Drug: Cylophosphamide
Drug: Doxorubicin
Drug: Paclitaxel
Drug: Carboplatin (Investigator discretion)
Biological: Pembrolizumab (Investigator discretion)

Registration Number: NCT05112536

Lead Sponsor: G1 Therapeutics, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 24

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
Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure (Class II-IV as defined by the New York Heart Association [NYHA] functional classification system)
Known history of stroke, cerebrovascular accident, severe/unstable angina, myocardial infarction, or coronary angioplasty/stenting/bypass grafting within 6 months prior to enrollment
Known serious active infection (e.g., human immunodeficiency virus [HIV], hepatitis B or C, tuberculosis).
Women who are pregnant or breastfeeding
Participation in other studies involving active treatment with investigational drug(s)
Prior hematopoietic stem cell or bone marrow transplantation

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Trilaciclib plus chemotherapy	Doxorubicin	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)
Trilaciclib plus chemotherapy	Pembrolizumab (Investigator discretion)	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)
Trilaciclib plus chemotherapy	Trilaciclib	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)
Trilaciclib plus chemotherapy	Cylophosphamide	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)
Trilaciclib plus chemotherapy	Carboplatin (Investigator discretion)	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)
Trilaciclib plus chemotherapy	Paclitaxel	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)

Primary Outcome Measures

Name	Time	Method
Immune-based Mechanism of Action	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.

Secondary Outcome Measures

Name	Time	Method
Pathologic Complete Response (pCR) Rate	Up to 26 weeks	Rate of pCR using the definition of ypT0/Tis ypN0 (i.e., no invasive residual tumor in breast or nodes; noninvasive breast residuals allowed) as assessed by the local pathologist.
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	Up to 28 weeks	Safety/tolerability as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Trial Locations

Locations (7): UCLA Department of Medicine - Hematology/Oncology
🇺🇸
Santa Monica, California, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸
Dallas, Texas, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
PIH Health
🇺🇸
Whittier, California, United States
Cancer and Blood Specialty Clinic
🇺🇸
Los Alamitos, California, United States
Nebraska Hematology-Oncology, P.C.
🇺🇸
Lincoln, Nebraska, United States
Virginia Oncology Associates
🇺🇸
Norfolk, Virginia, United States