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

Triple Negative Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05113966
• Other study ID #: G1T28-213
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 22, 2021
• Est. completion date: July 2024

Study information

• Verified date: March 2024
• Source: G1 Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 2, multicenter, open-label, single arm study evaluating the safety and efficacy of trilaciclib administered prior to sacituzumab govitecan-hziy in patients 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.

Description:

The study will include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of the first dose of study treatment and completes at the Safety Follow-up Visit. Trilaciclib and sacituzumab govitecan-hziy will be administered intravenously (IV) in 21-day cycles. Study drug administration will continue 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 occurs first. The first Survival Follow-up assessment should occur approximately 3 months after the Safety Follow-Up Visit and will continue every 3 months until the end of the study (or death).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: July 2024
• Est. primary completion date: November 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult ( =18 years of age), fFemale or male patient 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. Patient must have had documented disease progression during or after 2 lines of systemic chemotherapy treatment for unresectable, locally advanced or metastatic breast cancer (these regimens will qualify regardless of TNBC status at the time they were administered):

• One prior line of chemotherapy treatment could be in the neoadjuvant or adjuvant setting if progression occurred within 12 months of completion of chemotherapy;

• Patients must have prior taxane treatment in either the neoadjuvant, adjuvant, or advanced/metastatic setting OR patients must have demonstrated contraindications or are intolerant to taxanes;

• PARP inhibitors may meet the criteria for one of two lines of therapy if patient has documented germline BRCA1/BRCA2 mutation.

4. ECOG performance status of 0 or 1.

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

• Hemoglobin =9.0 g/dL

• Absolute neutrophil count (ANC) =1.5 × 109/L;

• Platelet count =100 × 109/L;

• Estimated glomerular filtration rate =30 mL/minute/1.73 m2;

• 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.

6. 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. Patients with known brain metastasis at enrollment.

3. Patients with known Gilbert's disease or known homozygous for the UGT1A1*28 allele.

4. Patients with bone-only disease.

5. Malignancies other than TNBC within 3 years prior to enrollment.

6. History of clinically significant gastrointestinal bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of enrollment.

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

8. Current use of immunosuppressive medication.

9. 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).

10. History of stroke or cerebrovascular accident within 6 months prior to first dose of study treatment.

11. Serious active infection or severe infection within 4 weeks prior to enrollment.

12. Prior hematopoietic stem cell or bone marrow transplantation.

13. Pregnant or lactating women

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Trilaciclib
Single-use, sterile powder to be reconstituted and further diluted with 250 mL of normal saline (sodium chloride solution 0.9%) or dextrose 5% in water (D5W)
• Sacituzumab Govitecan-hziy
10 mg/kg reconstituted to a concentration of 1.1 mg/mL to 3.4 mg/mL in normal saline

Locations

Country	Name	City	State
United States	Multicare Health System	Auburn	Washington
United States	Texas Oncology - Austin Central	Austin	Texas
United States	Comprehensive Blood & Cancer Center	Bakersfield	California
United States	Ironwood Physicians	Chandler	Arizona
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	Memorial Healthcare System	Hollywood	Florida
United States	Duly Health and Care	Joliet	Illinois
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Texas Oncology - Longview Cancer Center	Longview	Texas
United States	Los Angeles Hematology Oncology Medical Group	Los Angeles	California
United States	Valkyrie Clinical Trials	Los Angeles	California
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Oncology and Hematology Associates of Southwest Virginia, Inc	Roanoke	Virginia
United States	UCLA Hematology/Oncology Parkside	Santa Monica	California
United States	New England Cancer Specialists	Scarborough	Maine
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	Northwest Cancer Specialists, PC	Tigard	Oregon
United States	PIH Health	Whittier	California
United States	Minnesota Oncology Hematology, P.A.	Woodbury	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
G1 Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	Progression free survival defined as time from the date of first dose of study drug to radiographic disease progression using RECIST v1.1 or death due to any cause, whichever occurs first; for patients without disease progression or death, PFS will be calculated per censoring rules.	Up to 24 months
Secondary	Objective response rate	Objective response rate defined as the percentage of patients with best overall response of confirmed complete response or confirmed partial response per RECIST v1.1	Up to 36 months
Secondary	Clinical benefit rate	Clinical benefit rate defined as the percentage of patients with a 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 36 months
Secondary	Overall survival	Overall survival defined as time from the date of first dose of study drug to death due to any cause for those who died; or time to last contact known as alive for those who survived in the study (censored cases)	Up to 36 months
Secondary	Neutrophil-related myeloprotective effects	Occurrence of severe neutropenia (in Cycles 1/2 and the overall on study), occurrence of febrile neutropenia AEs , and occurrence of G-CSF administration	Up to 24 months
Secondary	RBC -related myeloprotective effects	Occurrence of Grade 3/4 decrease of hemoglobin, occurrence and number of RBC transfusions on/after Week 5, and occurrence of ESA administration	Up to 24 months
Secondary	Platelet-related myeloprotective effects	Occurrence of Grade 3/4 decrease of platelets and occurrence and number of platelet transfusions	Up to 24 months
Secondary	Safety and tolerability of trilaciclib	Occurrence and severity of AEs by NCI CTCAE v5.0	Up to 36 months