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

G1 Therapeutics

Status and phase

Completed

Phase 2

Conditions

Breast Cancer

Triple Negative Breast Cancer

Treatments

Drug: Paclitaxel

Drug: Trilaciclib

Drug: Cylophosphamide

Drug: Carboplatin (Investigator discretion)

Drug: Doxorubicin

Biological: Pembrolizumab (Investigator discretion)

Study type

Interventional

Funder types

Industry

Identifiers

NCT05112536

G1T28-212

Details and patient eligibility

About

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.

Enrollment

24 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

24 participants in 1 patient group

Trilaciclib plus chemotherapy

Experimental group

Description:

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)