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

Sponsor
G1 Therapeutics, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05112536
Collaborator
(none)
30
Enrollment
1
Location
1
Arm
15.2
Anticipated Duration (Months)
2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date :
Nov 19, 2021
Anticipated Primary Completion Date :
Aug 20, 2022
Anticipated Study Completion Date :
Feb 24, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: 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)

Drug: Trilaciclib
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.
Other Names:
  • COSELA®
  • G1T28
  • Drug: Cylophosphamide
    Cyclophosphamide administered IV every 2 weeks for the first 4 cycles (1-4), each cycle 2 weeks in length.
    Other Names:
  • CYTOXAN®
  • Drug: Doxorubicin
    Doxorubicin administered as an IV bolus every 2 weeks for the first 4 cycles (1-4), each cycle 2 weeks in length.
    Other Names:
  • ADRIAMYCIN®
  • Drug: Paclitaxel
    Paclitaxel administered weekly for the last 12 cycles (cycles 5-16), each cycle 1 week in length.
    Other Names:
  • TAXOL®
  • Drug: Carboplatin (Investigator discretion)
    Carboplatin, if given, is administered IV weekly at the start of paclitaxel administration, for the last 12 cycles (cycles 5-16).
    Other Names:
  • PARAPLATIN®
  • Biological: Pembrolizumab (Investigator discretion)
    Pembrolizumab, if given, is administered IV every 6 weeks throughout the treatment phase (cycles 1, 4, 9, 15).
    Other Names:
  • KEYTRUDA®
  • Outcome Measures

    Primary Outcome Measures

    1. Immune-based mechanism of action [Up to 8 days]

      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.

    Secondary Outcome Measures

    1. 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.

    2. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [Up to 28 weeks]

      Safety/tolerability as per CTCAE version 5.0

    Other Outcome Measures

    1. Intratumoral immune profile characterization following trilaciclib [Up to 26 weeks]

      Characterization of molecular and immune changes based on CD8+ T cell and Treg infiltration, quantified by RNA profiling of tumor tissue before study treatment, during study treatment, and at definitive surgery.

    2. Kinetics of the immune response in peripheral blood [Up to 26 weeks]

      Longitudinal immune changes in peripheral blood, measured by frequency of immune subsets and profiling of activation, maturation, and exhaustion status.

    3. Kinetics of T cell function and polyfunctionality [Up to 26 weeks]

      Ex-vivo measurement of cytokine production to determine T cell function and polyfunctionality.

    4. Molecular biomarkers for clinical responsiveness [Up to 26 weeks]

      pCR in patients by gene signatures determined in the tumor at baseline.

    5. CDK4/6 dependence for clinical responsiveness [Up to 26 weeks]

      pCR in patients by subgroups according to CDK4/6 dependence signatures.

    6. PD-L1 status and clinical responsiveness [Up to 26 weeks]

      pCR in patients by subgroups according to PD-L1 status, as measured by IHC.

    7. Immune response and clinical responsiveness [Up to 26 weeks]

      pCR in patients by frequency of immune subsets, immunological markers, and cytokines.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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 ≥ 2 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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Nebraska Hematology-Oncology, P.C.LincolnNebraskaUnited States68506

    Sponsors and Collaborators

    • G1 Therapeutics, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    G1 Therapeutics, Inc.
    ClinicalTrials.gov Identifier:
    NCT05112536
    Other Study ID Numbers:
    • G1T28-212
    First Posted:
    Nov 9, 2021
    Last Update Posted:
    Nov 30, 2021
    Last Verified:
    Nov 1, 2021

    Study Results

    No Results Posted as of Nov 30, 2021