Sequencing Antibody Drug Conjugates in ER+/HER2 LOW MBC

Breast Cancer Clinical Trial

— SERIES  

Official title:

SERIES: SEquencing Sacituzumab Govitecan AfteR T-DXd In ER+/HER2 LOW MetaStatic Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06263543
• Other study ID #: 2023-MAH-001
• Status: Recruiting
• Phase: Phase 2
• Start date: May 29, 2024
• Est. completion date: December 2026

Study information

• Verified date: May 2024
• Source: Baptist Health South Florida
• Contact: Reshma L Mahtani, D.O.
• Phone: (786) 596-2000
• Email: rmahtani[@]baptisthealth.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research study is to see if the medication sacituzumab govitecan (SG) is effective at the currently approved dose and schedule in people who have previously received trastuzumab deruxtecan (T-DXd) for the treatment of metastatic, hormone receptor positive (HR+)/human epidermal growth factor 2 low (HER2 low) breast cancer. Although SG is approved to treat metastatic HR+/HER2 negative breast cancer, the aim of this study is to determine if SG is still effective specifically in people who have already received T-DXd.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: December 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Provision of signed and dated informed consent form.

• Stated willingness to comply with all study procedures and availability for the duration of the study.

• Individuals = 18 years of age.

• Histologically confirmed metastatic or advanced and unresectable breast cancer that is HER2-low breast cancer (BC) by local testing with documented evidence of HR+/HER2-low defined as: [immunohistochemistry (IHC) 2+/in situ hybridization (ISH)- or IHC 1+ (ISH- or untested)] on either the primary or any metastatic site.

• Histologically confirmed metastatic or advanced and unresectable breast cancer that is estrogen receptor and/or progesterone receptor positive defined as >1% on any metastatic site or the primary tumor.

• Endocrine-refractory (as per investigator judgement) and may have received any number of prior endocrine therapies (alone or in combination with cyclin-dependent kinase (CDK)4/6 inhibitor, alpelisib, everolimus and/or capivasertib).

• Received a CDK4/6 inhibitor either alone or in combination with endocrine therapy (in the adjuvant or metastatic setting) with any duration of therapy permitted.

• Received at least 1 but no more than 4 prior systemic chemotherapy regimens in the metastatic setting

• Prior treatment with T-DXd (discontinued for progression and/or intolerance), which does not have to be the treatment immediately prior to enrollment on trial.

• Documented clinical and/or radiographic disease progression after most recent therapy, unless immediate prior therapy was T-DXd which was discontinued for toxicity.

• Measurable disease, as per RECIST V1.1

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 2.

• Adequate organ and bone marrow function within 28 days before randomization. For all parameters listed below, the most recent results available must be used:

1. Hemoglobin = 9 g/dL. Note: Red blood cell transfusion is not allowed within 1 week prior to screening assessment.

2. Absolute neutrophil count (ANC) = 1500/mm3. Note: Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment.

3. Platelet count = 100,000/mm3. Note: Platelet transfusion is not allowed within 1 week prior to registration.

4. Total bilirubin (TBL) = 1.5 × upper limit of normal (ULN) if no liver metastases or < 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastasis at baseline.

5. Alanine transaminase (ALT) and aspartate aminotransferase (AST) = 3 ×ULN or < 5 × ULN in patients with liver metastasis.

6. Serum albumin = 2.5 g/dL.

7. Creatinine clearance (CrCl) = 30 mL/min (calculated using the Cockcroft and Gault equation). Cockcroft-Gault equation: CrCl (mL/min) = [140 - age (years)] × weight (kg) 72 × serum creatinine (mg/dL) {× 0.85 for females}

8. International normalized ratio (INR) or prothrombin time (PT) and either partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) = 1.5 × ULN.

• Adequate treatment washout period before randomization, defined as:

1. Major surgery: = 3 weeks

2. Radiation therapy including palliative and/or stereotactic radiation therapy = 2 weeks

3. Hormonal therapy: = 2 weeks

4. Immunotherapy (non-antibody-based therapy): = 2 weeks

5. T-DXd: = 3 weeks

6. ADC's other than T-DXd: = 3 weeks

• Evidence of post-menopausal status or for individuals of childbearing potential must have a negative serum beta-human chorionic gonadotropin (ß-hCG) at screening or baseline. Individuals of childbearing potential are defined as those who are not surgically sterile (i.e., underwent bilateral tubal occlusion, bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal.

• Individuals of childbearing potential who are sexually active with a non-sterilized male partner must agree to use at least one highly effective method of contraception from the time of registration through final study treatment. Not all methods of contraception are highly effective.

• Non-sterilized male patients who are sexually active with a partner of childbearing potential must agree to use a condom with spermicide from registration and throughout duration of the study treatment.

The following are acceptable measures to prevent pregnancy:

• Abstinence (not having sexual relations with a person who can get you pregnant)

• Intrauterine Device (IUD)

• Vasectomy

• Sterilization

• Bilateral tubal occlusion

Exclusion Criteria:

• Locally advanced MBC (stage IIIc) in individuals who are candidates for curative intent therapy at the time of study enrollment.

• Patients with brain metastases (BM) except for asymptomatic treated BM not requiring ongoing corticosteroid treatment with stable lesions on baseline/screening brain MRI. Patients who require treatment of brain metastases are eligible after 14 days post receipt of surgery or radiation, if felt to be clinically stable and not requiring ongoing corticosteroid treatment.

• Active serious infection requiring ongoing antibiotics.

• History of an anaphylactic reaction to irinotecan.

• Pregnant or breastfeeding.

• Treatment with another investigational drug or other intervention within 21 days.

• Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.

• Any other condition that may put a participant at higher risk, at the discretion of the investigator.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Cancer
• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Sacituzumab govitecan
IV infusion of 10 mg/kg on Days 1 and 8 of each continuous and consecutive 21-day cycles. The first infusion will last approximately 3 hours and subsequent infusions will last 1-2 hours if prior infusions were well tolerated.

Locations

Country	Name	City	State
United States	Winship Cancer Institute at Emory University	Atlanta	Georgia
United States	UCLA Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Reshma L. Mahtani, D.O.	Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (2)

Rugo HS, Bardia A, Tolaney SM, Arteaga C, Cortes J, Sohn J, Marme F, Hong Q, Delaney RJ, Hafeez A, Andre F, Schmid P. TROPiCS-02: A Phase III study investigating sacituzumab govitecan in the treatment of HR+/HER2- metastatic breast cancer. Future Oncol. 2020 Apr;16(12):705-715. doi: 10.2217/fon-2020-0163. Epub 2020 Mar 30. — View Citation

Schmid P, Cortés J, Marmé F, Rugo HS, Tolaney SM, Oliveira M, Loirat D, Jhaveri K, Yoon OK, Motwani M, Wang H, Delaney RJ, Bardia A. Sacituzumab govitecan (SG) efficacy in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC) by HER2 immunohistochemistry (IHC) status in the phase III TROPiCS-02 study. Annals of Oncology. 2022; 33(Suppl7): S635-636.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR)	ORR will be assessed using Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). ORR is defined as the percentage of participants who received at least one dose of SG and have achieved a complete response (CR) or partial response (PR) as assessed by the local investigator.	24 months
Secondary	Clinical benefit rate (CBR)	CBR will be assessed using RECIST 1.1 and is defined as the percentage of participants who received at least one dose of SG and have achieved CR, PR, or stable disease (SD) as assessed by the local investigator.	24 months
Secondary	Progression-free survival (PFS)	PFS is defined as the duration of time from the date of first treatment until the date of the first radiological progressive disease (PD) per RECIST 1.1 or death from any cause, whichever comes first.	30 months
Secondary	Overall survival (OS)	OS is defined as the duration of time of first treatment until the date of death from any cause.	30 months
Secondary	Duration of response (DOR)	DOR is defined as the duration of time from the date of first response (CR or PR) until the date of the first radiological PD per RECIST 1.1 or death from any cause, whichever comes first.	30 months
Secondary	Global Quality of Life	Global Quality of Life is measured by European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30), a 30-item instrument designed to measure quality of life in individuals with cancer. The items are related to how difficult activities of daily living are, how often treatment or cancer-related symptoms occur and how much they interfere in daily activities and relationships. Each item is scored on a scale of 1 (not at all) to 4 (very much). Higher scores indicate worse quality of life.	24 months
Secondary	Treatment-related Adverse Events (AEs) and Serious Adverse Events (SAEs)	Percent of participants who experienced a treatment-related AE or SAE while on study.	30 months
Secondary	Laboratory and Vital Sign Abnormalities	Percent of participants who experienced a laboratory or vital sign abnormality that was considered clinically significant by the investigator while on study.	30 months
Secondary	Growth Factor Support	Percent of participants who required the use of growth factor support (administered at the discretion of the investigator) while on study.	30 months

External Links

•   Miami Cancer Institute