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

NCT05112536 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: G1T28-212
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 7

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.

Conditions

Triple Negative Breast Cancer; Breast Cancer

Keywords

Breast Cancer; Triple Negative Breast Cancer; CDK4/6 Inhibitor; trilaciclib dihydrochloride; Cosela; Immuno-oncology; Solid tumor; Chemotherapy-induced myelosuppression; Myeloprotective; Cyclin-dependent kinase 4/6 inhibitor; Neoadjuvant; HER2-negative; TNBC; Breast cancer surgery; Trilaciclib; Myeloprotection; pembrolizumab; carboplatin; doxorubicin; cyclophosphamide; Dose-dense anthracycline/cyclophosphamide; paclitaxel; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Immune-based Mechanism of Action

  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.

  Up to 8 days after lead-in trilaciclib dose

Secondary Outcomes (2)

• Pathologic Complete Response (pCR) Rate

  Up to 26 weeks

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  Up to 28 weeks

Study Arms (1)

Trilaciclib plus chemotherapy

EXPERIMENTAL

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)

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

Interventions

Trilaciclib DRUG

Trilaciclib is administered IV as monotherapy during the lead-in phase and administered prior to chemotherapy on each day chemotherapy is administered during the treatment phase.

Also known as: COSELA®, G1T28

Trilaciclib plus chemotherapy

Cylophosphamide DRUG

Cyclophosphamide administered IV every 2 weeks for the first 4 cycles (1-4), each cycle 2 weeks in length.

Also known as: CYTOXAN®

Trilaciclib plus chemotherapy

Doxorubicin DRUG

Doxorubicin administered as an IV bolus every 2 weeks for the first 4 cycles (1-4), each cycle 2 weeks in length.

Also known as: ADRIAMYCIN®

Trilaciclib plus chemotherapy

Paclitaxel DRUG

Paclitaxel administered weekly for the last 12 cycles (cycles 5-16), each cycle 1 week in length.

Also known as: TAXOL®

Trilaciclib plus chemotherapy

Carboplatin (Investigator discretion) DRUG

Carboplatin, if given, is administered IV weekly at the start of paclitaxel administration, for the last 12 cycles (cycles 5-16).

Also known as: PARAPLATIN®

Trilaciclib plus chemotherapy

Pembrolizumab (Investigator discretion) BIOLOGICAL

Pembrolizumab, if given, is administered IV every 6 weeks throughout the treatment phase (cycles 1, 4, 9, 15).

Also known as: KEYTRUDA®

Trilaciclib plus chemotherapy

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• G1 Therapeutics, Inc.: lead

Study Sites (7)

Cancer and Blood Specialty Clinic

Los Alamitos, California, 90720, United States

Location

UCLA Department of Medicine - Hematology/Oncology

Santa Monica, California, 90404, United States

Location

PIH Health

Whittier, California, 90602, United States

Location

Nebraska Hematology-Oncology, P.C.

Lincoln, Nebraska, 68506, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

trilaciclib; Cyclophosphamide; Doxorubicin; Paclitaxel; Carboplatin; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Coordination Complexes

Limitations and Caveats

A limitation of this study was the small number of participants.

Results Point of Contact

• Title: Clinical Trial Info.
• Organization: G1 Therapeutics, Inc.

clinicalinfo@g1therapeutics.com

919-213-9835

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 6, 2021
• First Posted: November 9, 2021
• Study Start: March 3, 2022
• Primary Completion: October 31, 2022
• Study Completion: March 13, 2023
• Last Updated: March 12, 2024
• Results First Posted: March 12, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)