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

Phase 2

Terminated

Conditions: Triple Negative Breast Cancer

Interventions: Drug: Trilaciclib
Drug: Sacituzumab Govitecan-hziy

Registration Number: NCT05113966

Lead Sponsor: G1 Therapeutics, Inc.

Brief Summary: 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.

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).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 30

Inclusion Criteria

Adult ( ≥18 years of age), female or male participant 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.
Measurable disease as defined by RECIST v1.1.
Considered to be eligible to receive sacituzumab govitecan-hziy treatment, in the Investigator's judgment.
Participants must have received 2 or more prior lines of systemic therapy, at least one of them in the metastatic setting.
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.
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 × 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.
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).
Predicted life expectancy of ≥3 months.
Contraceptive use by men or women should be consistent with local guidelines regarding the methods of contraception for those participating in clinical studies.
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.
Participants with known brain metastasis at enrollment.
Participants with known Gilbert's disease or known homozygous for the UGT1A1*28 allele.
Participants with bone-only disease.
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.
History of clinically significant gastrointestinal bleeding, intestinal obstruction, or gastrointestinal perforation within 6 months of enrollment.
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.
Receipt of any cytotoxic chemotherapy within 2 weeks or antibody treatment for cancer within 3 weeks prior to the first dose of study treatment.
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.
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).
Use of oral or IV antibiotics within 2 weeks prior to enrollment.
QT corrected interval using Fridericia's formula (QTcF) >480 msec at screening (confirmed on repeat). For participants with ventricular pacemakers, QTcF >500 msec.
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.
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.
Severe infection within 4 weeks prior to enrollment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
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.
Known hypersensitivity or allergy to irinotecan, SN-38, trilaciclib, or sacituzumab govitecan-hziy or any excipients of the aforementioned medications
Prior hematopoietic stem cell or bone marrow transplantation.
Pregnant or lactating women
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.
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).
Legal incapacity or limited legal capacity.
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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Trilaciclib + Sacituzumab Govitecan-hziy	Trilaciclib	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.
Trilaciclib + Sacituzumab Govitecan-hziy	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.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Up to approximately 23 months	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

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to approximately 24 months	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.
Clinical Benefit Rate (CBR)	Up to approximately 24 months	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
Duration of Objective Response (DOR)	Up to approximately 24 months	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.
Overall Survival (OS)	Up to approximately 24 months	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).
Number of Participants With Occurrence of Severe Neutropenia (SN)	Up to approximately 24 months	Occurrences of SN in Cycles 1 and 2 and the overall study are reported.
Participants With At Least One Occurrence of Febrile Neutropenia (FN)	Up to approximately 24 months	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.
Occurrence of Grade 3 or 4 Decreased Hemoglobin (Hgb)	Up to approximately 24 months	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).
Occurrence of Granulocyte Colony-stimulating Factor (G-CSF) Administration	Up to approximately 24 months	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.
Number of RBC Transfusions	From Week 5 up to approximately 24 months	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.
Number of Participants With Occurrence of Erythropoiesis-Stimulating Agent (ESA) Administration	Up to approximately 24 months	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.
Number of Participants With Occurrence of Grade 3 and 4 Decrease of Platelets	Up to approximately 24 months	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.
Number of Platelet Transfusions	Up to approximately 24 months	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).
Number of Participants With Occurrence of Serious Infections	Up to approximately 24 months	Participants experienced chemotherapy-induced myelosuppression faced severe clinical consequences such as serious infections are reported.
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)	From first administration of study treatment (Day 1) up to approximately 24 months	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.

Trial Locations

Locations (22): Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸
Dallas, Texas, United States
Comprehensive Cancer Centers of Nevada
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Las Vegas, Nevada, United States
Rocky Mountain Cancer Centers
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Denver, Colorado, United States
Comprehensive Blood & Cancer Center
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Bakersfield, California, United States
Ironwood Physicians
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Chandler, Arizona, United States
Los Angeles Hematology Oncology Medical Group
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Los Angeles, California, United States
Valkyrie Clinical Trials
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Los Angeles, California, United States
UCLA Hematology/Oncology Parkside
🇺🇸
Santa Monica, California, United States
PIH Health
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Whittier, California, United States
Memorial Healthcare System
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Hollywood, Florida, United States
Duly Health and Care
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Joliet, Illinois, United States
Northwest Cancer Specialists, PC
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Tigard, Oregon, United States
New England Cancer Specialists
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Scarborough, Maine, United States
Minnesota Oncology Hematology, P.A.
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Woodbury, Minnesota, United States
Inova Schar Cancer Institute
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Fairfax, Virginia, United States
Texas Oncology - Longview Cancer Center
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Longview, Texas, United States
Virginia Oncology Associates
🇺🇸
Norfolk, Virginia, United States
Oncology and Hematology Associates of Southwest Virginia, Inc
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Roanoke, Virginia, United States
Northwest Medical Specialties, PLLC
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Tacoma, Washington, United States
Multicare Health System
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Auburn, Washington, United States
Orlando Health Cancer Institute
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Orlando, Florida, United States
Texas Oncology - Austin Central
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Austin, Texas, United States