OncoMatch/Clinical Trials/NCT05455619
Evexomostat Plus PI3K or AKT Inhibitor and Fulvestrant in Patients With a PI3K Alteration and HR+/Her2- Breast Cancer
Is NCT05455619 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies Evexomostat for hr+/her2-negative breast cancer.
Treatment: Evexomostat — This is a Phase 1b/2, open-label, parallel-arms pilot study in men and post-menopausal women with hormone receptor positive (HR+), HER2- advanced or metastatic breast cancer with an alteration in the PI3K pathway, including a mutation of the PIK3CA gene, PTEN loss, or AKT1 mutation, designed to determine the safety of evexomostat (SDX-7320) plus standard of care treatment alpelisib (BYL-719) or capivasertib and fulvestrant (each combined, the 'triplet therapy'), to measure the severity and number of hyperglycemic events, and to assess clinical, anti-tumor benefit of the triplet therapy. The purpose of this study is: * to characterize the safety of the triplet drug combination consisting of either alpelisib or capivasertib (per the treating oncologist's choice) and fulvestrant plus evexomostat, * to test whether evexomostat, when given in combination with either alpelisib or capivasertib and fulvestrant will reduce the number and severity of hyperglycemic events and/or reduce the number or dose of anti-diabetic medications needed to control the hyperglycemia for metabolically normal patients and those deemed at risk for capivasertib and alpelisib-induced hyperglycemia (insulin resistance, as measured by HOMA-IR, baseline elevated HbA1c or well-controlled type 2 diabetes), and * to assess preliminary anti-tumor efficacy for each combination and changes in key biomarkers and quality of life in this patient population.
Check if I qualifyExtracted eligibility criteria
Cancer type
Breast Carcinoma
Biomarker criteria
Required: PIK3CA mutation
PIK3CA mutation
Required: PTEN loss
PTEN loss
Required: AKT1 mutation
AKT1 mutation
Performance status
ECOG 0–1(Restricted strenuous activity)
Prior therapy
Must have received: endocrine therapy — (neo)adjuvant or metastatic
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 combination with endocrine therapy) in the early stage or metastatic setting
Must have received: CDK4/6 inhibitor — (neo)adjuvant or metastatic
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 combination with endocrine therapy) in the early stage or metastatic setting
Cannot have received: fulvestrant (fulvestrant)
Exception: Patients whose disease progressed while receiving fulvestrant monotherapy are not allowed.
Patient is allowed prior fulvestrant treatment, provided they remain eligible for fulvestrant treatment. Patients whose disease progressed while receiving fulvestrant monotherapy are not allowed.
Lab requirements
Blood counts
Platelet count ≥140×10^9/L; Hemoglobin ≥ 9 g/dL; ANC ≥1500/mL; Albumin ≥ 3.5 gm/dL
Kidney function
Creatinine clearance ≥ 50 mL/min (Cockcroft-Gault or CKD-EPI or 24-hour urine); CKD grade ≤1
Liver function
ALT and AST ≤2.5×ULN (≤5×ULN with liver metastases); total bilirubin ≤1.5×ULN (≤3.0×ULN for Gilbert's syndrome or direct bilirubin ≤1.5×ULN)
adequate bone marrow and organ function as defined by the following laboratory values: Platelet count ≥140×10^9/L; ALT and AST ≤2.5×ULN (≤5×ULN with liver metastases); 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; 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. Alternatively, a 24-hour urine test can be performed to confirm renal sufficiency; Albumin ≥ 3.5 gm/dL.
Structured fields extracted by AI. May contain errors — verify against the official protocol.
US trial sites
- Loma Linda University Cancer Center · Loma Linda, California
- Hoag Memorial Hospital Presbyterian · Newport, California
- SHARP Healthcare · San Diego, California
- Miami Cancer Institute at Baptist Health · Miami, Florida
- Hope and Healing Cancer Services · Hinsdale, Illinois
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