Trilaciclib in Patients Receiving Sacituzumab Govitecan-hziy for Triple Negative Breast Cancer

A Phase 2, Single-Arm, Open-Label Study of Trilaciclib Administered Prior to Sacituzumab Govitecan-hziy in Patients With Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer Who Received at Least Two Prior Treatments, at Least One in the Metastatic Setting

This was a Phase 2, multicenter, open-label, single-arm study evaluating the safety and efficacy of trilaciclib administered prior to sacituzumab govitecan-hziy in participants with unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC) who received at least 2 prior treatments, at least 1 in the metastatic setting.

Study Overview

• Status: Terminated
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Drug: Trilaciclib; Drug: Sacituzumab Govitecan-hziy

Detailed Description

The study included 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase began on the day of the first dose of study treatment and was completed at the Safety Follow-up Visit. Trilaciclib and sacituzumab govitecan-hziy were administered intravenously (IV) in 21-day cycles. Study drug administration continued until progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or clinical progression as determined by the Investigator, unacceptable toxicity, withdrawal of consent, Investigator decision, or the end of the study, whichever occurred first. The first Survival Follow-up assessment occurred approximately 3 months after the Safety Follow-Up Visit and continued every 3 months until the end of the study (or death).

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Physicians
  • California
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood & Cancer Center
    • Los Angeles, California, United States, 90017
      • Los Angeles Hematology Oncology Medical Group
    • Los Angeles, California, United States, 90067
      • Valkyrie Clinical Trials
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology Parkside
    • Whittier, California, United States, 90602
      • PIH Health
  • Colorado
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Centers
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare System
    • Orlando, Florida, United States, 32806
      • Orlando Health Cancer Institute
  • Illinois
    • Joliet, Illinois, United States, 60435
      • Duly Health and Care
  • Maine
    • Scarborough, Maine, United States, 04704
      • New England Cancer Specialists
  • Minnesota
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology, P.A.
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada
  • Oregon
    • Tigard, Oregon, United States, 97223
      • Northwest Cancer Specialists, PC
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology - Austin Central
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • Longview, Texas, United States, 75601
      • Texas Oncology - Longview Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
    • Roanoke, Virginia, United States, 24014
      • Oncology and Hematology Associates of Southwest Virginia, Inc
  • Washington
    • Auburn, Washington, United States, 98001
      • MultiCare Health System
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult ( ≥18 years of age), female or male participant with measurable (per RECIST v1.1), unresectable locally advanced or metastatic TNBC
2. Documentation of histologically or cytologically confirmed ER-negative, PR-negative, and HER2-negative tumor per the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (ASCO/CAP) criteria.
3. Measurable disease as defined by RECIST v1.1.
4. Considered to be eligible to receive sacituzumab govitecan-hziy treatment, in the Investigator's judgment.
5. Participants must have received 2 or more prior lines of systemic therapy, at least one of them in the metastatic setting.
6. Radiation therapy for metastatic disease is permitted as long as the participant has at least 1 measurable lesion that has not been irradiated. Participants should be sufficiently recovered from the effects of radiation as determined by the Investigator but must have completed radiotherapy at least 2 weeks prior to enrollment.
7. ECOG performance status of 0 or 1.

8. Adequate organ function as demonstrated by the following laboratory values:

   • Hemoglobin ≥9.0 g/dL
   • Absolute neutrophil count (ANC) ≥1.5 × 10^9/L;
   • Platelet count ≥100 × 10^9/L;
   • Estimated glomerular filtration rate ≥30 mL/minute/1.73 m^2;
   • Total bilirubin ≤1.5 × upper limit of normal (ULN);
   • ALT and AST ≤3 × ULN in the absence of liver metastasis or ≤5 × ULN in the presence of liver metastasis.
9. Resolution of nonhematologic toxicities from prior systemic therapy, radiation therapy, or surgical procedures to Common Terminology Criteria for Adverse Events (CTCAE) ≤ Grade 1 (except alopecia or peripheral neuropathy that may be Grade 2 or less).
10. Predicted life expectancy of ≥3 months.
11. Contraceptive use by men or women should be consistent with local guidelines regarding the methods of contraception for those participating in clinical studies.
12. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.

Exclusion Criteria:

1. Prior treatment with trilaciclib, sacituzumab govitecan-hziy, irinotecan, Trop-2 antibody drug conjugate, or any therapy with a topoisomerase-1 payload.
2. Participants with known brain metastasis at enrollment.
3. Participants with known Gilbert's disease or known homozygous for the UGT1A1*28 allele.
4. Participants with bone-only disease.

5. Malignancies other than TNBC within 3 years prior to enrollment. Participants with malignancies of a negligible risk of metastasis or death (e.g., risk of metastasis or death <5% at 5 years as determined by the Investigator) are eligible provided they meet all of the following criteria:

   1. Malignancy treated with expected curative intent (e.g., adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent);
   2. No evidence of recurrence or metastasis by follow-up imaging and any disease-specific tumor markers.
6. History of clinically significant gastrointestinal bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of enrollment.
7. Receipt of any investigational medication within 4 weeks, or at least 5 half-lives, whichever is greater, prior to the first dose of study treatment.
8. Receipt of any cytotoxic chemotherapy within 2 weeks or antibody treatment for cancer within 3 weeks prior to the first dose of study treatment.

9. Receipt of any high dose systemic corticosteroids within 2 weeks prior to the first dose of study treatment.

   1. Low dose corticosteroids (≤20 mg prednisone or equivalent daily) are permitted if the dose is stable for 4 weeks, or if medically indicated as part of their pre-medications for infusions.
   2. Topical steroids and corticosteroid inhalers are allowed.

10. Current use of immunosuppressive medication, except for the following:

    1. Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
    2. Systemic corticosteroids at physiological doses ≤10 mg/day of prednisone or equivalent;
    3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
11. Use of oral or IV antibiotics within 2 weeks prior to enrollment.
12. QT corrected interval using Fridericia's formula (QTcF) >480 msec at screening (confirmed on repeat). For participants with ventricular pacemakers, QTcF >500 msec.
13. Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure (Class III or IV as defined by the New York Heart Association functional classification system).
14. History of stroke or cerebrovascular accident within 6 months prior to first dose of study treatment.
15. Known serious active infection such as, but not limited to, human immunodeficiency virus (HIV) (e.g., viral load indicative of HIV, HIV 1/2 antibodies), Hepatitis B (e.g., Hepatitis B surface antigen reactive or Hepatitis B DNA detected), Hepatitis C (e.g., Hepatitis C ribonucleic acid [quantitative] is detected) or tuberculosis.
16. Severe infection within 4 weeks prior to enrollment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
17. Other uncontrolled serious chronic disease or psychiatric condition that in the Investigator's opinion could affect participant safety, compliance, or follow-up in the protocol.
18. Known hypersensitivity or allergy to irinotecan, SN-38, trilaciclib, or sacituzumab govitecan-hziy or any excipients of the aforementioned medications
19. Prior hematopoietic stem cell or bone marrow transplantation.
20. Pregnant or lactating women
21. Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.

22. Received a live, attenuated vaccine within 4 weeks prior to the first dose of study treatment or anticipation that such a vaccine will be required during the study treatment period:

    a. Influenza vaccination should be given during influenza season only (approximately October through May in the Northern Hemisphere).

23. Legal incapacity or limited legal capacity.
24. Participants who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or participants who are employees of G1 Therapeutics, Inc. directly involved in the conduct of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Trilaciclib + Sacituzumab Govitecan-hziy; Participants received trilaciclib + sacituzumab govitecan-hziy on days 1 & 8 of a 21 day cycle. Trilaciclib is administered first, followed by sacituzumab govitecan-hziy. Administer diluted trilaciclib solution as a 30-minute IV infusion to be completed within 4 hours prior to the start of sacituzumab govitecan-hziy.

Drug: Trilaciclib; Single-use, sterile powder to be reconstituted and further diluted with 250 milliliters (mL) of normal saline (sodium chloride solution 0.9%) or dextrose 5% in water (D5W); Other Names: G1T28; CDK 4/6 inhibitor; Drug: Sacituzumab Govitecan-hziy; 10 milligram per kilogram (mg/kg) reconstituted to a concentration of 1.1 mg/mL to 3.4 mg/mL in normal saline; Other Names: IMMU-132; Trodelvy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression free survival was defined as the time (months) from the date of the first dose of the study drug to the date of documented radiographic disease progression per RECIST v1.1 or death due to any cause, whichever comes first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	Up to approximately 23 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the percentage of participants with the best overall response of confirmed complete response or confirmed partial response per RECIST v1.1 Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to approximately 24 months
Clinical Benefit Rate (CBR)	CBR was defined as the percentage of participants with the best overall response of confirmed complete response, confirmed partial response, or stable disease lasting 24 weeks or longer since the first date of study drug administration per RECIST v1.1	Up to approximately 24 months
Duration of Objective Response (DOR)	DOR was the time between the first objective response of CR or PR (confirmed) and the first date that progressive disease was documented or death, whichever comes first. DOR was only analyzed for the patients who had achieved objective responses.	Up to approximately 24 months
Overall Survival (OS)	OS was defined as the time (months) from the date of the first dose of the study drug to the date of death for participants who died in the study due to any cause or the time to the last contact date known to be alive for those participants who survived as of the data cutoff date for the planned OS analysis (censored cases).	Up to approximately 24 months
Number of Participants With Occurrence of Severe Neutropenia (SN)	Occurrences of SN in Cycles 1 and 2 and the overall study are reported.	Up to approximately 24 months
Participants With At Least One Occurrence of Febrile Neutropenia (FN)	FN was defined as a complication of cancer treatment. It is the development of a fever, alongside other signs of infection such as feeling unwell, shivers, and shakes in a participant with neutropenia.	Up to approximately 24 months
Occurrence of Granulocyte Colony-stimulating Factor (G-CSF) Administration	The number of cycles with G-CSF administrations for a participant was the total number of cycles where the participant received at least one dose of G-CSF, for participants who did not have any G-CSF use and those who were enrolled but did not receive any study treatment, a value of 0 was assigned.	Up to approximately 24 months
Occurrence of Grade 3 or 4 Decreased Hemoglobin (Hgb)	The occurrence of Grade 3 or 4 decreased hemoglobin (Hgb) for a participant was defined as having at least one Hgb value that was < 8.0 gram per deciliter (g/dL) among all scheduled or unscheduled assessments. It was a binary random variable (Yes or No).	Up to approximately 24 months
Number of RBC Transfusions	Based on the NCCN Clinical Practice Guidelines in Oncology for Hematopoietic Growth Factors Version 2.2020 and the AABB Clinical Practice Guidelines, the following RBC transfusion thresholds were recommended; however, the participant's clinical situation should always be the primary guiding factor when deciding to transfuse.; Transfusion is not indicated until the hemoglobin level is ≤7 g/dL for hospitalized adult hemodynamically stable participants .; An RBC transfusion threshold of ≤8 g/dL is recommended for participants undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease.	From Week 5 up to approximately 24 months
Number of Participants With Occurrence of Erythropoiesis-Stimulating Agent (ESA) Administration	If participants experienced chemotherapy-induced anemia (hemoglobin level <10 g/dL) after receiving the first dose of study treatment, ESAs may be used per ASCO guidelines to improve hematopoietic response and reduce the likelihood of RBC transfusion.	Up to approximately 24 months
Number of Participants With Occurrence of Grade 3 and 4 Decrease of Platelets	Grade 3 shows signs of mucosal bleeding, such as blood crusting in nostrils or nosebleeds, petechiae or purpura in the mouth, blood in the urine or stool, and heavy periods. Grade 4 shows signs of more severe mucosal bleeding or suspected internal bleeding, such as in the brain or lungs that requires immediate medical attention.	Up to approximately 24 months
Number of Platelet Transfusions	Platelet transfusion is recommended at a threshold of ≤10 x 10^9/L. Platelets should also be transfused in any participant who was bleeding with a platelet count <50 x 10^9/L (100 x 10^9/L for central nervous system or ocular bleeding).	Up to approximately 24 months
Number of Participants With Occurrence of Serious Infections	Participants experienced chemotherapy-induced myelosuppression faced severe clinical consequences such as serious infections are reported.	Up to approximately 24 months
Number of Participants Administered IV Antibiotics		Up to approximately 24 months
Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) and Non-serious Adverse Events (NSAEs)	AEs are defined as those events occurring or worsening after treatment has begun in the study. An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	From first administration of study treatment (Day 1) up to approximately 24 months

Collaborators and Investigators

• Sponsor: G1 Therapeutics, Inc.
• Investigators: Study Director: Clinical Conduct, G1 Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2021
• Primary Completion (Actual): November 10, 2023
• Study Completion (Actual): June 13, 2024

Study Registration Dates

• First Submitted: October 18, 2021
• First Submitted That Met QC Criteria: October 29, 2021
• First Posted (Actual): November 9, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 6, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: TNBC; Myelosuppression; Trodelvy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates; Sacituzumab govitecan
• Other Study ID Numbers: G1T28-213

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No