Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Gemcitabine and Carboplatin for Metastatic Triple-Negative Breast Cancer (TNBC) (PRESERVE 2)

• ClinicalTrials.gov Identifier: NCT04799249
• Recruitment Status: Active, not recruiting
• First Posted: March 16, 2021
• Last Update Posted: January 16, 2024
• Sponsor: G1 Therapeutics, Inc.
• Information provided by (Responsible Party): G1 Therapeutics, Inc.

Tracking Information

• First Submitted Date: February 18, 2021
• First Posted Date: March 16, 2021
• Last Update Posted Date: January 16, 2024
• Actual Study Start Date: April 15, 2021
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 11, 2021)

• Effect on Overall Survival (OS) [ Time Frame: Cohort 1:From date of randomization up to 39 months ]
  (Cohort 1):To evaluate the effect of trilaciclib on overall survival (OS) compared with placebo in patients receiving first-line gemcitabine and carboplatin.
• Effect on Overall Survival (OS) [ Time Frame: Cohort 2: From date of randomization up to 28 months ]
  (Cohort 2): To evaluate the effect of trilaciclib on OS compared with placebo in patients receiving gemcitabine and carboplatin as second-line therapy after treatment with a PD-1/PD-L1 inhibitor in the locally advanced unresectable/metastatic setting

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 11, 2021)

• Quality of life/Effects On Chemotherapy-Induced Fatigue [ Time Frame: Cycle 1 Day 1 (each cycle is 21 days) up to 14 months ]
  To assess the effect of trilaciclib on patients' quality of life as measured by time to first confirmed deterioration of fatigue compared with placebo in patients receiving gemcitabine and carboplatin
• Myeloprotective Effects [ Time Frame: Cycle 1 Day 1 (each cycle is 21 days) up to 14 months ]
  Occurrence of cytopenias, febrile neutropenia, hospitalization due to chemotherapy-induced myelosuppression, RBC and platelet transfusions, growth factor administration, and dose reductions and delays
• Progression Free Survival [ Time Frame: From date of randomization up to 14 months) ]
  To evaluate the effect of trilaciclib on progression-free survival (PFS) compared with placebo in patients receiving gemcitabine and carboplatin.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Gemcitabine and Carboplatin for Metastatic Triple-Negative Breast Cancer (TNBC)
• Official Title: A Phase 3, Randomized, Double-Blind Study of Trilaciclib or Placebo in Patients Receiving First- or Second-Line Gemcitabine and Carboplatin Chemotherapy for Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (PRESERVE 2)
• Brief Summary: This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of trilaciclib versus placebo administered prior to gemcitabine and carboplatin in patients receiving first- or second-line treatment for locally advanced unresectable/metastatic TNBC.

Detailed Description

This study will have two separate cohorts (Cohort 1 and Cohort 2). Both cohorts will follow the same general study conduct/design with similar primary and key secondary endpoints and identical treatment arms.

• Cohort 1 will evaluate patients receiving first-line therapy, regardless of programmed death-ligand 1 (PD-L1) status, who are programmed cell death protein 1 (PD-1)/PD-L1 inhibitor therapy naïve.
• Cohort 2 will evaluate PD-L1 positive patients receiving second-line therapy following prior PD-1/PD-L1 inhibitor therapy in the locally advanced unresectable/metastatic setting.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Double-Blind Trial

Primary Purpose: Treatment

Condition

• TNBC - Triple-Negative Breast Cancer
• Breast Cancer

Intervention

• Drug: Trilaciclib
  Trilaciclib administered IV over 30mins prior to chemotherapy on Day 1 and Day 8 of each 21-day cycle.
  Other Names:

  • G1T28
  • COSELA
• Drug: Placebo
  Placebo administered IV over 30mins prior to chemotherapy on Day 1 and Day 8 of each 21-day cycle.
  Other Names:

  • 0.9% normal saline
  • 5 % Dextrose in water (D5W)
• Drug: Gemcitabine
  Gemcitabine administered IV on Day 1 and Day 8 of each 21-day cycle.
• Drug: Carboplatin
  Carboplatin administered IV on Day 1 and Day 8 of each 21-day cycle.

Study Arms

• Experimental: Trilaciclib + gemcitabine + carboplatin
  Trilaciclib (240mg/m2) + gemcitabine (1000 mg/m2) and carboplatin (AUC 2)
  Interventions:

  • Drug: Trilaciclib
  • Drug: Gemcitabine
  • Drug: Carboplatin
• Placebo Comparator: Placebo + gemcitabine + carboplatin
  The subjects in the placebo arm will follow the same schedule as the trilaciclib arm, but will receive placebo instead of trilaciclib.
  Interventions:

  • Drug: Placebo
  • Drug: Gemcitabine
  • Drug: Carboplatin

• Publications *: Goel S, Tan AR, Rugo HS, Aftimos P, Andric Z, Beelen A, Zhang J, Yi JS, Malik R, O'Shaughnessy J. Trilaciclib prior to gemcitabine plus carboplatin for metastatic triple-negative breast cancer: phase III PRESERVE 2. Future Oncol. 2022 Oct;18(33):3701-3711. doi: 10.2217/fon-2022-0773. Epub 2022 Sep 22.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 25, 2022): 194
• Original Estimated Enrollment (submitted: March 11, 2021): 250
• Estimated Study Completion Date: October 25, 2024
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age >/= 18 years of age with evaluable locally advanced unresectable or metastatic TNBC.
2. Documentation of triple negative breast cancer (estrogen and progesterone receptor <1% and HER2-negative)

3. Prior systemic therapies (Cohort 1 only):

   1. No prior systemic therapy in the locally advanced unresectable/metastatic setting including chemotherapy, targeted therapy, immunotherapy, or investigational agents.
   2. Prior PD-1/PD-L1 inhibitor treatment is not permitted in any setting, including in the neoadjuvant setting.
   3. Time between completion of last treatment with curative intent and first metastatic recurrence must be ≥ 6 months.

4. Prior systemic therapies (Cohort 2 only):

   1. Documentation of PD-L1 positive status
   2. Treated with a PD-1/PD-L1 inhibitor for a minimum duration of 4 months in the locally advanced unresectable/metastatic setting and as the most recent therapy.
5. Radiation therapy for metastatic disease is permitted. There is no required minimum washout period for radiation therapy. Patients should be recovered from the effects of radiation.
6. Archival tumor tissue must be available or a fresh biopsy must be obtained, unless approved by the Medical Monitor.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Adequate organ function as demonstrated by normal laboratory values

Exclusion Criteria:

1. Prior treatment with gemcitabine in any setting.

2. Prior treatment with carboplatin in the locally advanced unresectable/metastatic setting.

   Prior carboplatin in the (neo)adjuvant/curative setting is permitted as long as it was completed ≥ 6 months prior to the first metastatic recurrence.

3. Presence of central nervous system (CNS) metastases and/or leptomeningeal disease requiring immediate treatment with radiation therapy or steroids.
4. Receipt of any cytotoxic chemotherapy within 14 days prior to the first dose of study drugs.
5. QTcF interval >480 msec at Screening (confirmed in triplicate). For patients with ventricular pacemakers, QTcF >500 msec.
6. Known hypersensitivity to carboplatin or other platinum-containing compounds, or mannitol
7. Pregnant or lactating women
8. Prior hematopoietic stem cell or bone marrow transplantation

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Bulgaria, China, France, Georgia, Moldova, Republic of, Poland, Russian Federation, Spain, Ukraine, United States
• Removed Location Countries: Serbia

Administrative Information

• NCT Number: NCT04799249
• Other Study ID Numbers: G1T28-208; 2020-004930-39 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: G1 Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: G1 Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Contact; G1 Therapeutics, Inc.

• PRS Account: G1 Therapeutics, Inc.
• Verification Date: May 2023