HR+/HER2-negative Breast Cancer study: Evexomostat
Official title Evexomostat Plus PI3K or AKT Inhibitor and Fulvestrant in Patients With a PI3K Alteration and HR+/Her2- Breast Cancer
ClinicalTrials.gov ID: NCT05455619
What this study is testing
What is Evexomostat (SDX-7320)?
an investigational drug being studied as a potential treatment for HR+/HER2‑negative advanced or metastatic breast cancer with PI3K pathway alterations. is designed to inhibit the enzyme MetAP2 as part of a synthetic copolymer‑drug conjugate.
Also referred to as SDX-7320.
Plain-language explanation of the investigational treatment. It is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- The study aims to see if the three‑drug combination is safe, whether it lowers high‑blood‑sugar events or the need for diabetes medicines, and to get early data on tumor response and quality of life.
- Who it's for
- Men and post‑menopausal women with HR+/HER2‑ advanced or metastatic breast cancer that shows a PI3K pathway alteration (such as a PIK3CA, PTEN loss, or AKT1 change).
- What's involved
- Participants will receive evexomostat together with either alpelisib or capivasertib and fulvestrant, and will have regular clinic visits, blood tests, and imaging to monitor safety, blood sugar, and tumor status.
- Time commitment
- The trial runs for several months, with multiple visits for treatment administration and monitoring throughout the study period.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Patient is an adult male or postmenopausal female ≥18 years old at the time of informed consent(s) and has signed informed consent(s) before any...
- Patient with histologically and/or cytologically confirmed diagnosis of HR+, HER2- breast cancer, as determined by the local laboratory.
- Patient has identified PI3K pathway alteration, defined as a PIK3CA mutation or PTEN loss or an AKT1 mutation using a Food and Drug Administration...
- Relapsed disease, not amenable to curative therapy, with documented evidence of progressive disease (PD) following receipt of both (neo) adjuvant...
- Newly diagnosed advanced breast cancer, with relapsed disease (i.e., documented evidence of PD) while receiving or after endocrine therapy plus a CDK...
See the full eligibility criteria
Who can join
- Patient is an adult male or postmenopausal female ≥18 years old at the time of informed consent(s) and has signed informed consent(s) before any trial related activities and according to local guidelines.
- Patient with histologically and/or cytologically confirmed diagnosis of HR+, HER2- breast cancer, as determined by the local laboratory.
- Patient has identified PI3K pathway alteration, defined as a PIK3CA mutation or PTEN loss or an AKT1 mutation using a Food and Drug Administration (FDA)-approved test, as determined either during Screening or was...
- Relapsed disease, not amenable to curative therapy, with documented evidence of progressive disease (PD) following receipt of both (neo) adjuvant endocrine therapy and a CDK 4/6 inhibitor therapy (either alone or in...
- Newly diagnosed advanced breast cancer, with relapsed disease (i.e., documented evidence of PD) while receiving or after endocrine therapy plus a CDK 4/6 inhibitor.
- Patient has measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Patient has an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤1
- Patient has a Screening fasting plasma glucose (FPG) level ≤140 mg/dL (7.7 mmol/L) and an HbA1c ≤6.4% (47 mmol/mol) for those taking alpelisib, or an HbA1c \<8% (64 mmol/mol) for those taking capivasertib.
- Patient has a body mass index (BMI) ≥ 20 kg/m2.
- ≥45 years of age and has not had menses for \>2 years.
- Amenorrheic for \>2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation.
- Post hysterectomy with oophorectomy. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound.
- Patient is allowed prior fulvestrant treatment, provided they remain eligible for fulvestrant treatment. Patients whose disease progressed while receiving fulvestrant monotherapy are not allowed.
- Patient is allowed prior mTOR or PI3K inhibitor treatment for patients otherwise eligible for capivasertib treatment.
- Patient is allowed up to one (1) prior chemotherapy for their metastatic disease.
- Patient agrees to, and is willing and able to arrive at the hospital/clinic in a fasted state (\>8 hours) on designated fasting days.
- Platelet count ≥140×109/L
- In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×the upper limit of normal (ULN). If the patient has liver metastases, ALT and AST ≤5×ULN.
- Total bilirubin ≤1.5×ULN except for patient with Gilbert's syndrome who may only be included if the total bilirubin is ≤3.0×ULN or direct bilirubin ≤1.5×ULN.
- Fasting serum amylase ≤2×ULN.
- Fasting serum lipase ≤1.5×ULN.
- Hemoglobin ≥ 9 g/dL.
- Absolute neutrophil count (ANC) ≥1500/mL.
- Creatinine clearance ≥ 50 mL/min using either the Cockcroft-Gault equation or the CKD-EPI formula for calculation of eGFR, or has chronic kidney disease (CKD) grade ≤1 as evidenced by a treating nephrologist.
- Albumin ≥ 3.5 gm/dL.
- Patient has inflammatory breast cancer at screening.
- Patient has known primary brain malignancy, active brain metastasis or active central nervous system pathology or is considered by the Investigator to be neurologically unstable.
- Patient has a known hypersensitivity to evexomostat, fulvestrant, alpelisib, or capivasertib, or to any of their excipients.
- Patient has an established diagnosis of type 1 diabetes mellitus or uncontrolled (based on fasting plasma glucose [FPG] \>140mg/dL or HbA1c ≥6.5% for patients assigned alpelisib) or HbA1c for patients assigned to...
- Patient has had major surgery within 30 days or minor surgery within 14 days prior to the first study drug dose, or has not recovered from major side effects from prior surgery.
- Patient has ongoing toxicities related to prior anti-cancer therapies that have not resolved to Grade 0 for bone marrow toxicities or ≤Grade 1 for other toxicities, per National Cancer Institute Common Terminology...
- Patient has a Child Pugh score of B or C.
- Patient has uncontrolled human immunodeficiency virus (HIV) infection.
- Patient has received radio therapy ≤4 weeks or limited field radiation for palliation ≤2 weeks prior to enrollment, and who has not recovered to ≤Grade 1 from related side effects of such therapy (with the exception of...
- Patient has a concurrent malignancy other than breast cancer or had a malignancy other than breast cancer within 2 years of enrollment, with the exception of adequately treated, basal or squamous cell carcinoma...
- Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the drug alpelisib or capivasertib (e.g., ulcerative diseases, uncontrolled nausea, vomiting...
- Patient has currently documented or unresolved pneumonitis/interstitial lung disease (the chest computed tomography [CT] scan performed before start of study treatment for the purpose of tumor assessment should be...
- Strong cytochrome P450 3A4 (CYP3A4) inducers
- Inhibitors of breast cancer resistance protein (BCRP)
- Sulfonylurea-based anti-diabetic drugs (e.g., glipizide, glyburide, etc.)
- Patient has a history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis.
- Patient has unresolved osteonecrosis of the jaw (unless they are being considered for treated with capivasertib - i.e., this exclusion is only for patients being considered for alpelisib).
- Patient has a history of severe cutaneous reaction, such as Stevens-Johnson Syndrome (SJS), erythema multiforme (EM), toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS).
- Patient is currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.
- Patient is nursing (lactating) or pregnant confirmed by a positive serum (hCG) test prior to initiating study treatment.
- Patient participated in a prior investigational study within 21 days prior to the start of study treatment or within 5 half-lives of the investigational product, whichever is longer.
- Patient has any other concurrent, severe and/or uncontrolled medical condition that would, in the Investigator's judgement, contra-indicate patient participation in the clinical study (e.g., chronic active hepatitis...
- Patient is not able to understand nor to comply with study instructions and requirements, including fasting requirements.
The study team makes the final eligibility decision.
Where it is enrolling
- Loma Linda, California, United States
- Newport, California, United States
- San Diego, California, United States
- Miami, Florida, United States
- Hinsdale, Illinois, United States
- Ypsilanti, Michigan, United States
- Cleveland, Ohio, United States
- Hershey, Pennsylvania, United States
- Nashville, Tennessee, United States
- Laredo, Texas, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part, but confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
This study is enrolling now at Loma Linda, California, United States; Newport, California, United States; San Diego, California, United States; Miami, Florida, United States; Hinsdale, Illinois, United States; Ypsilanti, Michigan, United States and 4 more locations. Enter your location above to see the nearest enrolling site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.