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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Istituto Europeo Di Oncologia S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 May 2026 → ongoing

Decision date (initial)

2025-10-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

GE Healthcare Limited · GUARDANT HEALTH, INC. · Menarini Berlin Chemie

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the activity of elacestrant plus exemestane

Secondary objectives 5

1. To assess the safety of elacestrant plus exemestane per CTCAE v.5.0
2. To assess the survival of patients receiving elacestrant plus exemestane
3. To assess the activity of elacestrant plus exemestane, in terms of disease debulking
4. To assess the change in quality of life in patients receiving elacestrant plus exemestane
5. To describe basal and variation of SUV uptake of FES (lesion per lesion and patient per patient) and its predictive and prognostic correlation

Conditions and MedDRA coding

Metastatic hormone receptor-positive/HER2-negative breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. At least 18 years old
2. 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
3. Appropriate candidates for endocrine therapy (no visceral crisis, highly symptomatic disease or rapidly progressing disease)
4. Measurable disease per RECIST or bone only disease with evaluable lesions
5. ≥50% of measurable lesions defined as avid (SUVmax≥1.5) at 18F-FES-PET/CT
6. 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)
7. ECOG performance status 0 or 1
8. Adequate organ function

Exclusion criteria 7

1. Prior treatment with fulvestrant, elacestrant or investigational SERD or ER antagonist in metastatic or early disease
2. Prior treatment with tamoxifen or SERD alone or combined with CDK4/6i in the metastatic setting
3. Bisphosphonates or RANKL inhibitors initiated or dose changed < 3 months prior to first dose of study drug
4. Radiation therapy within 14 days (28 days for brain lesions) before the first dose of study drug
5. Presence of symptomatic metastatic visceral disease or meningeal disease
6. Pregnancy at the time of the study entry
7. Diagnosis of inflammatory breast cancer and chest wall disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 6-month PFS rate per RECIST v 1.1

Secondary endpoints 5

1. Adverse Events per CTCAE 5.0
2. Median Overall Survival
3. Overall Response Rate per RECIST 1.1
4. Median QoL change from baseline to week 8 of treatment measured by EORTC QLQ-C30 and FACT-ES v.4 questionaries
5. 6-months Progression-free survival (PFS) rate per RECIST 1.1 according to baseline FES-SUV and SUV variation of FES

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Istituto Europeo Di Oncologia S.r.l.

Sponsor organisation

Istituto Europeo Di Oncologia S.r.l.

Address

Via Giuseppe Ripamonti 435

City

Milan

Postcode

20141

Country

Italy

Scientific contact point

Organisation

Istituto Europeo Di Oncologia S.r.l.

Contact name

Giuseppe Curigliano

Public contact point

Organisation

Istituto Europeo Di Oncologia S.r.l.

Contact name

Giuseppe Curigliano

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications