Breast CancerPhase 2COMBINE-01NCT07395336
Elacestrant and Exemestane for Patients With Pretreated HR+/HER2- Metastatic Breast Cancer and [18F] FES-avid Lesions (COMBINE)
A Phase 2 study testing elacestrant and exemestane in people with Breast Cancer, run by European Institute of Oncology at 1 site in Italy.
Trial summary
Single agent endocrine therapy (ET), with selective estrogen receptor degraders (SERDs; i.e. fulvestrant or elacestrant), is an option for patients with pre-treated hormone receptor-positive (HR+) breast cancer (BC) with indolent behaviour beyond the first line therapy with CDK4/6 inhibitors (CDK4/6i) + ET, in order… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- elacestrant and exemestane
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteItaly
- Study dates
- 11 May 2026to Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must be at least 18 years old;
- Must have a histologically- or cytologically-proven diagnosis of 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
- Must be appropriate candidates for endocrine therapy (no visceral crisis, highly symptomatic disease or rapidly progressing disease)
- Must have 1 of the following as defined by RECIST v1.1:
- Measurable disease
- Bone only disease with evaluable lesions. Subjects must have at least 1 lytic or mixed lytic/blastic bone lesion; blastic lesions only are not evaluable and allowed. Subjects who have had prior radiation to bone must have at least 1 evaluable lesion in a nonirradiated area.
Show all 14Show fewer
- ≥50% of measurable lesions defined as avid (SUVmax≥1.5) at 18F-FES-PET/CT;
- Must have HR+ and HER2- disease at the last previous biopsy. ER and HER2 testing must be performed in the following manner:
- Documentation of ER+ tumor with ≥ 10% staining by immunohistochemistry (IHC), with or without PgR positivity AND
- Documentation of HER2- tumor with an IHC result of 0 or 1+ for cellular membrane protein expression or an in situ hybridization negative result as defined in the 2023 ASCO recommendations for HER2 testing (Wolff, 2013; Wolff, 2018; Wolff 2023)
- 8. Must have progressed during or within 28 days of completion of prior treatment with a CDK4/6 inhibitor in combination with anastrozole or letrozole (+ LHRH agonist for male or premenopausal female patients).
- This treatment has to be received in first line setting for metastatic disease (with abemaciclib, ribociclib or palbociclib)
- Discontinuation of prior CDK4/6 inhibitor due to toxicity, in the absence of progression, will not fulfill this criterion
- Patients must have received the combination treatment for at least 12 months and there must have been evidence of disease control (stable disease [SD], partial response [PR] or complete response [CR] as best response) 9. Must have received no other treatment after the CDK4/6 inhibitor combined with endocrine therapy 10. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Who cannot join
- Prior treatment with fulvestrant, elacestrant or investigational SERD or ER antagonist in metastatic or early disease (e.g., D-0502, GDC-0810, GDC-0927, GDC-9545, G1T-48, LSZ102, AZD9496, SAR439859, ZN-c5, H3B-6545, bazedoxifene, lasofoxifene)
- Prior treatment with tamoxifen or SERD alone or combined with CDK4/6i in metastatic setting
- Any other endocrine therapy < 14 days before first dose of study drug
- Any prior treatment after first line with CDK4/6i in 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Carmine Valenza, MD contact
Italy1 site, 1 recruiting
- Recruiting
European Institute of Oncology
Milan, Italy, 20141
Giuseppe Curigliano, MD, 0257489439, giuseppe.curigliano@ieo.it
About this study
Official title: Elacestrant and Exemestane for Patients With Pretreated HR+/HER2- Metastatic Breast Cancer and [18F] FES-avid Lesions (COMBINE): a Proof-of-concept Phase 2 Clinical Trial
Single agent endocrine therapy (ET), with selective estrogen receptor degraders (SERDs; i.e. fulvestrant or elacestrant), is an option for patients with pre-treated hormone receptor-positive (HR+) breast cancer (BC) with indolent behaviour beyond the first line therapy with CDK4/6 inhibitors (CDK4/6i) + ET, in order to spare the adverse events related to chemotherapy.
Anyway, the efficacy of endocrine monotherapy in patients progressing on first line therapy is low, because of the occurrence of endocrine resistance mechanisms, like the HR loss and the switch to HR-negative subtype, caused by the selective pressure of first line therapy; furthermore, biomarkers for patient selection are missing.
Read more
Recently, the 16a-[18F]fluoro-17b-estradiol positron emission tomography ([18F]FES-PET) demonstrated a sensitivity and specificity of 86% in estrogen receptor expression prediction; therefore it is a promising tool to select patients progressing on CDK4/6i + ET without HR loss.
Single agent endocrine therapy (ET), with selective estrogen receptor degraders (SERDs; i.e. fulvestrant or elacestrant), is an option for patients with pre-treated hormone receptor-positive (HR+) breast cancer (BC) with indolent behaviour beyond the first line therapy with target cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) + ET, in order to spare the adverse events related to chemotherapy.
Anyway, the efficacy of endocrine monotherapy in patients progressing on first line therapy is low, because of the occurrence of endocrine resistance mechanisms, like the Hormon Receptor (HR) loss and the switch to HR-negative subtype, caused by the selective pressure of first line therapy; furthermore, biomarkers for patient selection are missing.
Recently, the 16a-[18F] fluoro-17b-estradiol positron emission tomography ([18F] FES-PET) demonstrated a sensitivity and specificity of 86% in estrogen receptor expression prediction; therefore it is a promising tool to select patients progressing on CDK4/6i + ET without HR loss.
The combination of endocrine agent, namely fulvestrant 250 mg plus anastrozole 1 mg (an aromatase inhibitor), demonstrated to provide an overall survival benefit in patients with Hormon Receptor positive Breast Cancer only in first line setting but not in patients progressing to ET. However, meanwhile, fulvestrant 500 mg was demonstrated to be superior to fulvestrant 250 mg in 2nd line setting, and oral SERDs (e.g. Elacestrant, Camizestrant) were demonstrated to be superior in terms of Progression Free Survival to fulvestrant 500 mg in patients progressing on ET, in the subgroup of patients with estrogen receptor 1 gene (ESR1) mutations.
Hypothesis: there is a strong rationale to assess the safety and the activity of Elacestrant plus exemestane in patients with pre-treated HR+ and Human Epidermal Growth Factor Receptor 2 negative (HER2-) metastatic breast cancer and at least 50% of [18F]FES-avid measurable lesions, using [18F]FES PET/CT to evaluate the early response to treatment.
- Conditions
- Breast Cancer
- Being tested
- elacestrant and exemestane
- Keywords
- elacestrant, exemestane, HR+, HER2-
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
elacestrant and exemestaneDrug
elacestrant 345 mg die and exemestane 25 mg die
| Study group | Role | What they receive |
|---|---|---|
| elacestrant and exemestane | Experimental | elacestrant 345 mg die and exemestane 25 mg die Receives: Drug: elacestrant and exemestane |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month Progression Free Survival (PFS) rate per RECIST (Response Evaluation Criteria in Solid Tumors) v1.1
Measured: 6 month
Secondary outcomes (6)
Adverse Event (AE) per Common Terminology Criteria for Adverse Events (CTCAE) 5.0
Measured: up to 3 years
Median Overall Survival (OS)
Measured: up to 3 years
Overall Response Rate (ORR) per RECIST v1.1
Measured: up to 3 years
Median QoL (QLQ-C30) change from baseline to week 8 of treatment
Median QoL change from baseline to week 8 of treatment measured by EORTC QLQ-C30 av.4 questionarie
Measured: up to 8 weeks
Median QoL (FACT-ES) change from baseline to week 8 of treatment
Median QoL change from baseline to week 8 of treatment measured by EORTC FACT-ES v.4 questionarie
Measured: up to 8 weeks
6-months Progression Free Survival (PFS) rate per RECIST v1.1 according to baseline FES-SUV and SUV variation of FES
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2026
- Study start11 May 2026
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by European Institute of OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giuseppe Curigliano, Principal investigator, European Institute of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07395336
- Sponsor's protocol ID
- UID 4270
- Acronym
- COMBINE-01
- Status last verified
- May 2026
- First submitted
- 5 Dec 2025
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Elacestrant and Exemestane for Patients With Pretreated HR+/HER2- Metastatic Breast Cancer and [18F] FES-avid Lesions (COMBINE): a Proof-of-concept Phase 2 Clinical Trial
- ClinicalTrials.gov ID
- NCT07395336
- Acronym / sponsor ID
- COMBINE-01 / UID 4270
- Conditions
- Breast Cancer
- Keywords
- elacestrant, exemestane, HR+, HER2-
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- European Institute of OncologyUniversity, hospital or other
- Study start
- 11 May 2026 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 9 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Single agent endocrine therapy (ET), with selective estrogen receptor degraders (SERDs; i.e. fulvestrant or elacestrant), is an option for patients with pre-treated hormone receptor-positive (HR+) breast cancer (BC) with indolent behaviour beyond the first line therapy with CDK4/6 inhibitors (CDK4/6i) + ET, in order to spare the adverse events related to chemotherapy.
Anyway, the efficacy of endocrine monotherapy in patients progressing on first line therapy is low, because of the occurrence of endocrine resistance mechanisms, like the HR loss and the switch to HR-negative subtype, caused by the selective pressure of first line therapy; furthermore, biomarkers for patient selection are missing.
Recently, the 16a-[18F]fluoro-17b-estradiol positron emission tomography ([18F]FES-PET) demonstrated a sensitivity and specificity of 86% in estrogen receptor expression prediction; therefore it is a promising tool to select patients progressing on CDK4/6i + ET without HR loss.
Single agent endocrine therapy (ET), with selective estrogen receptor degraders (SERDs; i.e. fulvestrant or elacestrant), is an option for patients with pre-treated hormone receptor-positive (HR+) breast cancer (BC) with indolent behaviour beyond the first line therapy with target cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) + ET, in order to spare the adverse events related to chemotherapy.
Anyway, the efficacy of endocrine monotherapy in patients progressing on first line therapy is low, because of the occurrence of endocrine resistance mechanisms, like the Hormon Receptor (HR) loss and the switch to HR-negative subtype, caused by the selective pressure of first line therapy; furthermore, biomarkers for patient selection are missing.
Recently, the 16a-[18F] fluoro-17b-estradiol positron emission tomography ([18F] FES-PET) demonstrated a sensitivity and specificity of 86% in estrogen receptor expression prediction; therefore it is a promising tool to select patients progressing on CDK4/6i + ET without HR loss.
The combination of endocrine agent, namely fulvestrant 250 mg plus anastrozole 1 mg (an aromatase inhibitor), demonstrated to provide an overall survival benefit in patients with Hormon Receptor positive Breast Cancer only in first line setting but not in patients progressing to ET. However, meanwhile, fulvestrant 500 mg was demonstrated to be superior to fulvestrant 250 mg in 2nd line setting, and oral SERDs (e.g. Elacestrant, Camizestrant) were demonstrated to be superior in terms of Progression Free Survival to fulvestrant 500 mg in patients progressing on ET, in the subgroup of patients with estrogen receptor 1 gene (ESR1) mutations.
Hypothesis: there is a strong rationale to assess the safety and the activity of Elacestrant plus exemestane in patients with pre-treated HR+ and Human Epidermal Growth Factor Receptor 2 negative (HER2-) metastatic breast cancer and at least 50% of [18F]FES-avid measurable lesions, using [18F]FES PET/CT to evaluate the early response to treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| elacestrant and exemestane | Experimental | Drug: elacestrant and exemestaneelacestrant 345 mg die and exemestane 25 mg die |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Must be at least 18 years old;
- Must have a histologically- or cytologically-proven diagnosis of 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
- Must be appropriate candidates for endocrine therapy (no visceral crisis, highly symptomatic disease or rapidly progressing disease)
- Must have 1 of the following as defined by RECIST v1.1:
- ≥50% of measurable lesions defined as avid (SUVmax≥1.5) at 18F-FES-PET/CT;
Key exclusion criteria (6 listed)
- Prior treatment with fulvestrant, elacestrant or investigational SERD or ER antagonist in metastatic or early disease (e.g., D-0502, GDC-0810, GDC-0927, GDC-9545, G1T-48, LSZ102, AZD9496, SAR439859, ZN-c5, H3B-6545, bazedoxifene, lasofoxifene)
- Prior treatment with tamoxifen or SERD alone or combined with CDK4/6i in metastatic setting
- Any other endocrine therapy < 14 days before first dose of study drug
- Any prior treatment after first line with CDK4/6i in metastatic setting
- Bisphosphonates or RANKL inhibitors initiated or dose changed < 3 months prior to first dose of study drug
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| elacestrant and exemestaneelacestrant 345 mg die and exemestane 25 mg die | Drug | elacestrant and exemestane |
Primary outcome
6-month Progression Free Survival (PFS) rate per RECIST (Response Evaluation Criteria in Solid Tumors) v1.1
Time frame: 6 month
6 secondary outcomes
Adverse Event (AE) per Common Terminology Criteria for Adverse Events (CTCAE) 5.0
Time frame: up to 3 years
Median Overall Survival (OS)
Time frame: up to 3 years
Overall Response Rate (ORR) per RECIST v1.1
Time frame: up to 3 years
Median QoL (QLQ-C30) change from baseline to week 8 of treatment
Time frame: up to 8 weeks
Median QoL (FACT-ES) change from baseline to week 8 of treatment
Time frame: up to 8 weeks
6-months Progression Free Survival (PFS) rate per RECIST v1.1 according to baseline FES-SUV and SUV variation of FES
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Carmine Valenza, MD contact
Giuseppe Curigliano principal investigator
European Institute of Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing elacestrant and exemestane in people with Breast Cancer, run by European Institute of Oncology at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giuseppe Curigliano, MD (0257489439, giuseppe.curigliano@ieo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-month Progression Free Survival (PFS) rate per RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 (time frame: 6 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.