The combination of Elacestrant and exemestane for patients with pretreated metastatic breast cancer expressing hormone receptors and non-expressing HER2, with lesions which uptake [18F]FES-avid (COMBINE): a proof-of-concept phase 2 clinical trial

Prior treatment

• Prior treatment with fulvestrant, elacestrant or investigational SERD or ER antagonist in metastatic or early disease
• Prior treatment with tamoxifen or SERD alone or combined with CDK4/6i in the metastatic setting
• Bisphosphonates or RANKL inhibitors initiated or dose changed < 3 months prior to first dose of study drug
• Radiation therapy within 14 days (28 days for brain lesions) before the first dose of study drug

Other illness

• Presence of symptomatic metastatic visceral disease or meningeal disease
• Diagnosis of inflammatory breast cancer and chest wall disease

Other

• Pregnancy at the time of the study entry

• At least 18 years old
• Histologically - or cytologically-proven diagnosis of HR+ (Estrogen Receptor: ≥10%)/HER2- carcinoma of the breast with evidence of either locally advanced disease not amenable to resection or radiation therapy with curative intent or metastatic disease not amenable to curative therapy
• Appropriate candidates for endocrine therapy (no visceral crisis, highly symptomatic disease or rapidly progressing disease)
• Measurable disease per RECIST or bone only disease with evaluable lesions
• ≥50% of measurable lesions defined as avid (SUVmax≥1.5) at 18F-FES-PET/CT
• Progressed on prior treatment with a CDK4/6 inhibitor in combination with anastrozole or letrozole (+ LHRH agonist for male or premenopausal female patients), in first line setting for metastatic disease, for at least 12 months and there must have been evidence of disease control (at least stable disease per RECIST v.1.1)
• ECOG performance status 0 or 1
• Adequate organ function