RECRUITING

Sequencing Antibody Drug Conjugates in ER+/HER2 LOW MBC

Conditions

Breast Cancer Metastatic Breast Cancer Advanced Breast Cancer Hormone-receptor-positive Breast Cancer Human Epidermal Growth Factor 2 Low Breast Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-06-17

Study Completion:2026-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06263543

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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, everolimus, alpelisib, acapivasertib or inavolisib). * 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 ADCs count as a line of systemic therapy. * 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 enrollment. 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/mm\^3. Note: Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment. 3. Platelet count ≥ 100,000/mm\^3. 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 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. * Abstinence (not having sexual relations with a person who can get you pregnant) * Non-hormonal Intrauterine Device (IUD) * Vasectomy * Sterilization * Bilateral tubal occlusion	* 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.

Inclusion Criteria

Exclusion 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, everolimus, alpelisib, acapivasertib or inavolisib).
* 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 ADCs count as a line of systemic therapy.
* 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 enrollment. 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/mm\^3. Note: Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment.
3. Platelet count ≥ 100,000/mm\^3. 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 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.
* Abstinence (not having sexual relations with a person who can get you pregnant)
* Non-hormonal Intrauterine Device (IUD)
* Vasectomy
* Sterilization
* Bilateral tubal occlusion

* 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.

Contacts and Locations

Study Contact

Reshma L Mahtani, D.O.

CONTACT

(786) 596-2000

rmahtani@baptisthealth.net

Krystal Fernandez

CONTACT

(786) 596-2000

krystal.fernandez@baptisthealth.net

Principal Investigator

Reshma L Mahtani, D.O.

PRINCIPAL_INVESTIGATOR

Miami Cancer Institute at Baptist Health, Inc.

Study Locations (Sites)

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, California, 90404

United States

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176

United States

Winship Cancer Institute at Emory University

Atlanta, Georgia, 30322

United States

Collaborators and Investigators

Sponsor: Reshma L. Mahtani, D.O.

Reshma L Mahtani, D.O., PRINCIPAL_INVESTIGATOR, Miami Cancer Institute at Baptist Health, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-06-17

Study Completion Date2026-12

Study Record Updates

Study Start Date2024-06-17

Study Completion Date2026-12

Terms related to this study

Additional Relevant MeSH Terms

Breast Cancer
Metastatic Breast Cancer
Advanced Breast Cancer
Hormone-receptor-positive Breast Cancer
Human Epidermal Growth Factor 2 Low Breast Cancer