Hormone Receptor-Positive HER2-Negative Advanced Breast CancerPhase 2LaPemERLANCT05286437

Phase II Lenvatinib and Pembrolizumab in Endocrine Resistant Breast Cancer With Letrozole

A Phase 2 study testing Oral Lenvatinib + Intravenous (IV) Pembrolizumab + Oral Letrozole in people with Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer, run by National Cancer Centre, Singapore at 1 site in Singapore.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 21 to 99 years
Conditions the study is for: Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer
What is being tested?: Oral Lenvatinib + Intravenous (IV) Pembrolizumab + Oral Letrozole
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: 1 siteSingapore
Study dates: 15 Feb 2023to 31 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 21 to 99 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male/female participants who are at least 21 years of age on the day of signing informed consent, with histologically or cytologically confirmed diagnosis of metastatic or locally advanced carcinoma of the breast not amenable to treatment with curative intent, will be enrolled in this study.
Disease progression after treatment with at least 1 line of palliative endocrine therapy in the metastatic setting.
There is no limit to the number of lines of prior palliative endocrine therapy. (Prior aromatase inhibitor in the curative and/or palliative setting is allowed.)
Prior targeted therapy in the locally advanced (recurrent or progressed) or metastatic setting, such as CDK4/6 inhibitors, mTOR inhibitors, PI3K inhibitors, is allowed with no limit to the number of lines of targeted therapy (prior Lenvatinib is not allowed).
Maximum of 1 line of palliative chemotherapy is allowed.
A chemotherapy line in advanced disease is an anticancer regimen(s) that contains at least 1 cytotoxic chemotherapy agent and was discontinued due to progression. If a cytotoxic chemotherapy regimen was discontinued for a reason other than disease progression then this regimen does not count as a "prior line of chemotherapy".

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Antibody-drug conjugate will be considered as cytotoxic chemotherapy in the assessment of the lines of treatment.
ER positive and/or PgR positive breast cancer (based on most recent tumor biopsy or archived tumor specimen) according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, assessed locally and defined as at least 1% of tumor cells stained positive.
HER2-negative tumor assessed locally and defined as meeting one of the following sets of criteria:
HER2 IHC score of 0 or 1+
HER2 IHC score of 2+ accompanied by a negative fluorescence, chromogenic, or silver in situ hybridization test indicating the absence of HER2 gene amplification
HER2/CEP17 ratio of < 2.0 based on the most recent tumor biopsy (or archived tumor sample).
For women: postmenopausal or premenopausal/perimenopausal status, defined as follows: Postmenopausal, as defined by at least one of the following criteria:
Age ≥ 60 years
Age < 60 years and ≥ 12 months of amenorrhea plus follicle-stimulating hormone (FSH) and plasma estradiol levels within postmenopausal range by local laboratory assessment, in the absence of oral contraceptive pills, hormone replacement therapy, or gonadotropin-releasing hormone agonist or antagonist
Documented bilateral oophorectomy (≥14 days prior to first treatment on Day 1 of Cycle 1 and recovery from surgery to baseline) Premenopausal or perimenopausal, defined as not meeting the criteria for postmenopausal, and willing to undergo and maintain treatment with approved LHRH-agonist therapy for the duration of study treatment LHRH-agonist therapy may be initiated 14-28 days prior to commencement of letrozole, and continued 4-weekly.
For men: willing to undergo and maintain treatment with approved LHRH-agonist therapy for the duration of study treatment; LHRH-agonist therapy may be initiated 14-28 days prior to commencement of letrozole, and continued 4-weekly.
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
Not a woman of childbearing potential (WOCBP) as defined in protocol OR
A WOCBP who agrees to follow the contraceptive guidance in protocol during the treatment period and for at least 120 days (corresponding to time needed to eliminate pembrolizumab and/or any active comparator/combination) plus 30 days (a menstruation cycle) after the last dose of study treatment.
A male participant must agree to use a contraception during the treatment period and for at least 120 days, corresponding to time needed to eliminate pembrolizumab plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period.
The participant provides written informed consent for the trial.
Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Availability of tumor sample:
Patient should have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institutions guidelines. Patient must be willing to undergo a new tumor biopsy at screening. Bone metastases are not acceptable.
A representative tumor sample obtained after progression on the patients most recent endocrine therapy must be submitted
In the event that a post-progression sample is not available and a new biopsy cannot be obtained, enrolment may be considered after documented discussion with the Principal Investigator and the study team for a waiver.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
Life expectancy of more than 12 weeks.
Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Cycle 1 Day -14.
Have adequate organ and haematological functions as defined in the protocol.

Who cannot join

A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
Has received prior Lenvatinib.
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (or 5 times the half-life, whichever is shorter) prior to allocation. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible.
Lack of adequate recovery from any toxicity and/or complications from any toxicity and/or complications from major surgery prior to starting therapy.

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Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks (or 5 times the half-life for systemic agent(s), whichever is shorter) prior to the first dose of study intervention.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
Has severe hypersensitivity (≥Grade 3) to Pembrolizumab, Lenvatinib, Letrozole and/or any of its excipients.
Has 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). Replacement therapy (eg thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. Subjects with T3, free T3 or free T4 abnormalities at screening who are asymptomatic can be eligible, but will need to be monitored closely with correction of abnormalities as clinically indicated.
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Subjects having >1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥1 g/24-hour will be ineligible.
Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of Lenvatinib.
New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months.
Prolongation of QTc interval to >480 msec.
Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
Serious nonhealing wound, ulcer, or bone fracture
Has an active infection requiring systemic therapy. Hepatitis B and/or C infection may be allowed if controlled (see criterion 23 below).
Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. The presence of hepatitis B core antibody (HBcAb) will not be an exclusion criterion provided HBsAg is negative and Hepatitis B virus DNA is not detected.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant 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.
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
Has had an allogenic tissue/solid organ transplant.

Trial locations and contacts

1 site in 1 country.

Singapore1 site

National Cancer Centre Singapore
Singapore, 169610

Other trials in Singapore

About this study

Official title: Lenvatinib and Pembrolizumab in Endocrine Resistant Breast Cancer With Letrozole in the Advanced Setting - a Phase II Study

This is a phase II study testing the combination of Pembrolizumab with Lenvatinib, a multi-kinase inhibitor that has activity against vascular endothelial growth factor receptors 1-3 (VEGFR1-3), fibroblast growth factor receptors 1-4 (FGFR1-4), ret protooncogene (RET), platelet-derived growth factor receptor-alpha (PDGFR-alpha) and KIT (a stem cell factor receptor), and letrozole, a non-steroidal aromatase inhibitor, in advanced hormone receptor (HR) positive human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC) that has progressed on/after standard endocrine therapy.

Conditions: Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer
Being tested: Oral Lenvatinib + Intravenous (IV) Pembrolizumab + Oral Letrozole
Keywords: Advanced Breast Cancer

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Oral Lenvatinib + Intravenous (IV) Pembrolizumab + Oral LetrozoleDrug
Lenvatinib and Letrozole will be given orally (PO) daily from Day -14, while Pembrolizumab will be administered intravenously during week 1 of each 6-weekly cycle from Cycle 1 Day 1 (C1D1), with daily Lenvatinib and Letrozole.

Study groups in NCT05286437
Study group	Role	What they receive
Intervention	Experimental	Oral Lenvatinib + Intravenous (IV) Pembrolizumab + Oral Letrozole Receives: Drug: Oral Lenvatinib + Intravenous (IV) Pembrolizumab + Oral Letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

Objective Response Rate (ORR) per RECIST version 1.1
The efficacy of Pembrolizumab, Lenvatinib and Letrozole.
ORR is defined as the proportion of subjects who have best objective response (BOR) of CR or PR at the time of data cutoff, based on RECIST version 1.1.
Measured: Up to 2 years.

Secondary outcomes (6)

Progression-Free Survival (PFS) per RECIST version 1.1
PFS is defined as the time from the first study dose date (at the D-14 Lenvatinib + Letrozole run-in phase) to the date of first documentation of confirmed disease progression or death (whichever occurs first) according to RECIST version 1.1.
Measured: Up to 3 years after End of Treatment (estimated).
Progression-Free Survival (PFS) per iRECIST
PFS is defined as the time from the first study dose date (at the D-14 Lenvatinib + Letrozole run-in phase) to the date of first documentation of confirmed disease progression or death (whichever occurs first) according to iRECIST criteria.
Measured: Up to 3 years after End of Treatment (estimated).
Objective Response Rate (ORR) per iRECIST
ORR is defined as the proportion of subjects who have best objective response (BOR) of CR or PR at the time of data cutoff, based on iRECIST criteria.
Measured: Up to 2 years.
Duration of Response (DOR)
DOR is defined as the time from the date the criteria are met for an CR or PR (whichever is recorded first) to the date the disease progression is objectively documented. If a subject has no record of disease progression, then the subject's data will be censored at the last available tumour assessment.
Measured: Up to 3 years after End of Treatment (estimated).
Clinical Benefit Rate (CBR)
CBR is defined as the percentage of patients with CRs, PRs, and durable (≥24 weeks) stable disease (SD).
Measured: Up to 3 years after End of Treatment (estimated).
Overall Survival (OS)
OS is measured from the start date of the treatment period (at the D-14 lenvatinib + letrozole run-in phase) until date of death from any cause.
Measured: Up to 3 years after End of Treatment (estimated).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Feb 202331 Dec 2028

First posted18 Mar 2022
Study start15 Feb 2023
Primary completion31 Dec 2026 (estimated)
Study completion31 Dec 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Hormone Receptor-Positive HER2-Negative Advanced Breast CancerStudies of the same condition, open and under way.
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: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05286437
Sponsor's protocol ID: LaPemERLA
Acronym: LaPemERLA
Status last verified: Jul 2026
First submitted: 9 Mar 2022
Last updated: 14 Jul 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Study at a glance

From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Lenvatinib and Pembrolizumab in Endocrine Resistant Breast Cancer With Letrozole in the Advanced Setting - a Phase II Study
ClinicalTrials.gov ID: NCT05286437
Acronym / sponsor ID: LaPemERLA / LaPemERLA
Conditions: Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer
Keywords: Advanced Breast Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 40 participants (actual)
Lead sponsor: National Cancer Centre, SingaporeUniversity, hospital or other
Collaborators: MSD Pharma (Singapore) Pte Ltd
Study start: 15 Feb 2023 (actual)
Primary completion: 31 Dec 2026 (estimated)
Study completion: 31 Dec 2028 (estimated)
First posted: 18 Mar 2022 (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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Intervention	Experimental	Drug: Oral Lenvatinib + Intravenous (IV) Pembrolizumab + Oral LetrozoleOral Lenvatinib + Intravenous (IV) Pembrolizumab + Oral Letrozole

Who may qualify

Ages: 21 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (31 listed)

Male/female participants who are at least 21 years of age on the day of signing informed consent, with histologically or cytologically confirmed diagnosis of metastatic or locally advanced carcinoma of the breast not amenable to treatment with curative intent, will be enrolled in this study.
Disease progression after treatment with at least 1 line of palliative endocrine therapy in the metastatic setting.
ER positive and/or PgR positive breast cancer (based on most recent tumor biopsy or archived tumor specimen) according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines, assessed locally and defined as at least 1% of tumor cells stained positive.
HER2-negative tumor assessed locally and defined as meeting one of the following sets of criteria:
For women: postmenopausal or premenopausal/perimenopausal status, defined as follows: Postmenopausal, as defined by at least one of the following criteria:

Key exclusion criteria (28 listed)

A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
Has received prior Lenvatinib.
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (or 5 times the half-life, whichever is shorter) prior to allocation. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible.

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
Oral Lenvatinib + Intravenous (IV) Pembrolizumab + Oral LetrozoleLenvatinib and Letrozole will be given orally (PO) daily from Day -14, while Pembrolizumab will be administered intravenously during week 1 of each 6-weekly cycle from Cycle 1 Day 1 (C1D1), with daily Lenvatinib and Letrozole.	Drug	Intervention

Primary outcome

Objective Response Rate (ORR) per RECIST version 1.1
Time frame: Up to 2 years.
The efficacy of Pembrolizumab, Lenvatinib and Letrozole. ORR is defined as the proportion of subjects who have best objective response (BOR) of CR or PR at the time of data cutoff, based on RECIST version 1.1.

6 secondary outcomes

Progression-Free Survival (PFS) per RECIST version 1.1
Time frame: Up to 3 years after End of Treatment (estimated).
Progression-Free Survival (PFS) per iRECIST
Time frame: Up to 3 years after End of Treatment (estimated).
Objective Response Rate (ORR) per iRECIST
Time frame: Up to 2 years.
Duration of Response (DOR)
Time frame: Up to 3 years after End of Treatment (estimated).
Clinical Benefit Rate (CBR)
Time frame: Up to 3 years after End of Treatment (estimated).
Overall Survival (OS)
Time frame: Up to 3 years after End of Treatment (estimated).

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 Jul 2026.

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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.

Dr. Yoon-Sim YAP principal investigator

National Cancer Centre, Singapore

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 31 inclusion and 28 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: under way, not looking for participants, as of the sponsor's last update on 14 Jul 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 Singapore. 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?

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?

Objective Response Rate (ORR) per RECIST version 1.1 (time frame: Up to 2 years.). 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 NCT05286437.

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 Jul 2026.