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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: Trilaciclib
* Drug: Sacituzumab Govitecan-hziy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult ( ≥18 years of age), fFemale or male patient with measurable (per RECIST v1.1), unresectable locally advanced or metastatic TNBC 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. 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. ECOG performance status of 0 or 1. 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. 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: Prior treatment with trilaciclib, sacituzumab govitecan-hziy, irinotecan, Trop-2 antibody drug conjugate, or any therapy with a topoisomerase-1 payload. Patients with known brain metastasis at enrollment. Patients with known Gilbert's disease or known homozygous for the UGT1A1*28 allele. Patients with bone-only disease. Malignancies other than TNBC within 3 years prior to enrollment. History of clinically significant gastrointestinal bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of enrollment. Receipt of any high dose systemic corticosteroids within 2 weeks prior to the first dose of study treatment. Current use of immunosuppressive medication. 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). History of stroke or cerebrovascular accident within 6 months prior to first dose of study treatment. Serious active infection or severe infection within 4 weeks prior to enrollment. Prior hematopoietic stem cell or bone marrow transplantation. Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trilaciclib + Sacituzumab Govitecan-hziy<br>During the Treatment Phase patients will receive 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<br>* 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)<br>* Other names: CDK 4/6 inhibitor;Drug: Sacituzumab Govitecan-hziy<br>* 10 mg/kg reconstituted to a concentration of 1.1 mg/mL to 3.4 mg/mL in normal saline<br>* Other names: IMMU-132;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Platelet-related myeloprotective effects | Occurrence of Grade 3/4 decrease of platelets and occurrence and number of platelet transfusions | Up to 24 months | 
| Safety and tolerability of trilaciclib | Occurrence and severity of AEs by NCI CTCAE v5.0 | Up to 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TNBC, Trodelvy, Myelosuppression