Premenopausal Breast CancerPhase 1/2PEERNCT02990845
Pembrolizumab and Exemestane/ Leuprolide in Premenopausal HR+/ HER2- Locally Advanced or Metastatic Breast Cancer
A Phase 1/2 study testing Pembrolizumab/ Exemestane/ Leuprolide in people with Premenopausal Breast Cancer, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
This is an open-label, single-arm, multicenter, pilot study of pembrolizumab, exemestane, and leuprolide for subjects being resistant for front-line hormonal therapy for inoperable locally advanced or metastatic hormonal receptor positive (HR+)/ Human epidermal growth factor receptor 2 (HER2) negative breast cancer. Read more about this study
- Who is it for?
- Ages 20 years and older, women only
- Conditions the study is for
- Premenopausal Breast Cancer
- What is being tested?
- Pembrolizumab/ Exemestane/ Leuprolide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteTaiwan
- Study dates
- 15 Sep 2017to 16 Aug 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 20 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be a female adult aged more than 20-year-old at the time of informed consent.
- Have histologically confirmed ER positive (defined as ≥1%) and/ or PR positive (defined as ≥1%) breast cancer.
- Have histologically confirmed HER2-negative breast cancer as defined by IHC ≤ 2+, and/or FISH negative.
- Have radiological or objective evidence of inoperable locally advanced or metastatic breast cancer.
- Be premenopausal or peri-menopausal. Premenopausal or peri-menopausal status is defined as below:
- Last menstrual period within the last 12 months OR
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- With a plasma estradiol ≥10pg/ml and FSH ≤40IU/L
- Be resistant to front line hormonal therapy, as defined as one of the following criteria:
- Have become inoperable locally advanced or metastatic disease within one year of adjuvant hormonal therapy.
- Fail at least 2 line of prior hormonal therapy for locally advanced or metastatic breast cancer.
- Have history of disease progressed within 6 months during 1st line hormone therapy for locally advanced or metastatic disease.
- Prior exemestane usage is allowed, but the patient number is limited to ≤10 patients.
- Have archival primary tumor specimen from diagnosis.
- Have metastatic tumor specimen before enrollment.
- Have measurable disease as per RECIST 1.1 or non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
- Have ECOG performance status 0 or 1 assessed within 10 days of treatment initiation.
- Have adequate bone marrow and organ function.
- For women of childbearing potential must have a negative serum beta-hCG or urine pregnancy test obtained within 3 days before starting treatment.
- Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section - Contraception, for the course of the study through 120 days after the last dose of study medication.
- Be able to comply with study procedures and sign an informed consent.
Who cannot join
- Is currently participating in an investigational agent study.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study treatment. Physiological steroid replacement is allowed.
- Has had chemotherapy within 2 weeks prior to the first dose of study treatment or has not recovered from side effects (i.e. Grade 1 at baseline) except alopecia related to prior therapy.
- Is a hepatitis B or C carrier.
- Has concurrent malignancy other than non-melanoma skin cancer.
- Is not able to undergo metastatic tumor biopsy.
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- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Note: Replacement therapy (i.e. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137) or has previously participated in Merck pembrolizumab clinical trials.
- Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
- Is lactating, pregnant, or unwilling to employ birth control methods during the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study of Pembrolizumab and Exemestane/ Leuprolide in Premenopausal Hormone Receptor Positive/ HER2 Negative Locally Advanced or Metastatic Breast Cancer
This is an open-label, single-arm, multicenter, pilot study of pembrolizumab, exemestane, and leuprolide for subjects being resistant for front-line hormonal therapy for inoperable locally advanced or metastatic hormonal receptor positive (HR+)/ Human epidermal growth factor receptor 2 (HER2) negative breast cancer. All the patients will be included in the final tolerability and preliminary efficacy analysis. The efficacy objectives including PFS, overall response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR). Adverse effects will be recorded according to CTCAE v4.0.
- Conditions
- Premenopausal Breast Cancer
- Being tested
- Pembrolizumab/ Exemestane/ Leuprolide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab/ Exemestane/ LeuprolideDrug
Dose level 1 (Pembrolizumab 150 mg IV Q2W); Dose level -1 (Pembrolizumab 100 mg IV Q2W); Dose level -2 (Pembrolizumab 50 mg IV Q2W) Combination with Exemestane 25 mg PO QD, and Leuprolide 3.75 mg SC Q4W
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab/ Exemestane/ Leuprolide | Experimental | Dose level 1 (Pembrolizumab 150 mg IV Q2W); Dose level -1 (Pembrolizumab 100 mg IV Q2W); Dose level -2 (Pembrolizumab 50 mg IV Q2W) Combination with Exemestane 25 mg PO QD, and Leuprolide 3.75 mg SC Q4W Receives: Drug: Pembrolizumab/ Exemestane/ Leuprolide |
What is being measured
The primary outcome is the main question the study is designed to answer.
The PFS rate at 8 months
To estimate the efficacy of the combination of pembrolizumab and exemestane/ leuprolide in premenopausal with hormone receptor positive/ HER2 negative locally advanced or metastatic breast cancer patients, as defined by PFS rate at 8 months.
Measured: 28 months
Secondary outcomes (5)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: 28 months
The PFS based on RECIST 1.1
Measured: 28 months
The overall response rate (ORR) based on RECIST 1.1
Measured: 28 months
The clinical benefit rate (CBR) based on RECIST 1.1
Measured: 28 months
The duration of overall response (DOR) based on RECIST 1.1
Measured: 28 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2016 (estimated)
- Study start15 Sep 2017
- Primary completion16 Aug 2022
- Study completion16 Aug 2022
Why it stopped: The enrolment became difficult, as most of the premenopausal women decided to receive ovarian ablation for health insurance reimbursement for CDK4/6 inhibitor for the first-line treatment, making them ineligible for joining the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Premenopausal Breast CancerStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02990845
- Sponsor's protocol ID
- 201610003MIFA
- Acronym
- PEER
- Status last verified
- Feb 2023
- First submitted
- 1 Dec 2016
- Last updated
- 22 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Chen IC, Lin CH, Chang DY, Wei-Wu Chen T, Wang MY, Ma WL, Lin YT, Huang SM, Hsu CL, Lu YS. Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer. Cell Rep Med. 2025 Jan 21;6(1):101879. doi: 10.1016/j.xcrm.2024.101879. Epub 2024 Dec 26.
PubMed 39730000
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Pembrolizumab and Exemestane/ Leuprolide in Premenopausal Hormone Receptor Positive/ HER2 Negative Locally Advanced or Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT02990845
- Acronym / sponsor ID
- PEER / 201610003MIFA
- Conditions
- Premenopausal Breast Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The enrolment became difficult, as most of the premenopausal women decided to receive ovarian ablation for health insurance reimbursement for CDK4/6 inhibitor for the first-line treatment, making them ineligible for joining the study.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 15 Sep 2017 (actual)
- Primary completion
- 16 Aug 2022 (actual)
- Study completion
- 16 Aug 2022 (actual)
- First posted
- 13 Dec 2016 (estimated)
- 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.
This is an open-label, single-arm, multicenter, pilot study of pembrolizumab, exemestane, and leuprolide for subjects being resistant for front-line hormonal therapy for inoperable locally advanced or metastatic hormonal receptor positive (HR+)/ Human epidermal growth factor receptor 2 (HER2) negative breast cancer. All the patients will be included in the final tolerability and preliminary efficacy analysis. The efficacy objectives including PFS, overall response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR). Adverse effects will be recorded according to CTCAE v4.0.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab/ Exemestane/ Leuprolide | Experimental | Drug: Pembrolizumab/ Exemestane/ LeuprolideDose level 1 (Pembrolizumab 150 mg IV Q2W); Dose level -1 (Pembrolizumab 100 mg IV Q2W); Dose level -2 (Pembrolizumab 50 mg IV Q2W) Combination with Exemestane 25 mg PO QD, and Leuprolide 3.75 mg SC Q4W |
Who may qualify
- Ages
- 20 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Be a female adult aged more than 20-year-old at the time of informed consent.
- Have histologically confirmed ER positive (defined as ≥1%) and/ or PR positive (defined as ≥1%) breast cancer.
- Have histologically confirmed HER2-negative breast cancer as defined by IHC ≤ 2+, and/or FISH negative.
- Have radiological or objective evidence of inoperable locally advanced or metastatic breast cancer.
- Be premenopausal or peri-menopausal. Premenopausal or peri-menopausal status is defined as below:
Key exclusion criteria (14 listed)
- Is currently participating in an investigational agent study.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 1 week prior to the first dose of study treatment. Physiological steroid replacement is allowed.
- Has had chemotherapy within 2 weeks prior to the first dose of study treatment or has not recovered from side effects (i.e. Grade 1 at baseline) except alopecia related to prior therapy.
- Is a hepatitis B or C carrier.
- Has concurrent malignancy other than non-melanoma skin cancer.
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 |
|---|---|---|
| Pembrolizumab/ Exemestane/ LeuprolideDose level 1 (Pembrolizumab 150 mg IV Q2W); Dose level -1 (Pembrolizumab 100 mg IV Q2W); Dose level -2 (Pembrolizumab 50 mg IV Q2W) Combination with Exemestane 25 mg PO QD, and Leuprolide 3.75 mg SC Q4W | Drug | Pembrolizumab/ Exemestane/ Leuprolide |
Primary outcome
The PFS rate at 8 months
Time frame: 28 months
To estimate the efficacy of the combination of pembrolizumab and exemestane/ leuprolide in premenopausal with hormone receptor positive/ HER2 negative locally advanced or metastatic breast cancer patients, as defined by PFS rate at 8 months.
5 secondary outcomes
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 28 months
The PFS based on RECIST 1.1
Time frame: 28 months
The overall response rate (ORR) based on RECIST 1.1
Time frame: 28 months
The clinical benefit rate (CBR) based on RECIST 1.1
Time frame: 28 months
The duration of overall response (DOR) based on RECIST 1.1
Time frame: 28 months
Results and safety
The study was stopped early (reason given: The enrolment became difficult, as most of the premenopausal women decided to receive ovarian ablation for health insurance reimbursement for CDK4/6 inhibitor for the first-line treatment, making them ineligible for joining the study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2023.
- Derived from this study: PubMed 39730000Chen IC, Lin CH, Chang DY, Wei-Wu Chen T, Wang MY, Ma WL, Lin YT, Huang SM, Hsu CL, Lu YS. Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer. Cell Rep Med. 2025 Jan 21;6(1):101879. doi: 10.1016/j.xcrm.2024.101879. Epub 2024 Dec 26.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pembrolizumab/ Exemestane/ Leuprolide in people with Premenopausal Breast Cancer, run by National Taiwan University Hospital at 1 site in Taiwan.
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 20 inclusion and 14 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: stopped early, as of the sponsor's last update on 22 Feb 2023. 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 Taiwan. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study was stopped early (reason given: The enrolment became difficult, as most of the premenopausal women decided to receive ovarian ablation for health insurance reimbursement for CDK4/6 inhibitor for the first-line treatment, making them ineligible for joining the study.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The PFS rate at 8 months (time frame: 28 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02990845, which also lists 1 linked publication.
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 22 Feb 2023.