HER2-Negative Breast CancerPhase 2NCT03989089

Study of Pembrolizumab in Metastatic HER2-negative Breast Cancer Patients With APOBEC3B Mutation

A Phase 2 study testing Pembrolizumab in people with HER2-Negative Breast Cancer, run by University of Malaya at 2 sites in 2 countries.

Active, not recruiting

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

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: HER2-Negative Breast Cancer
What is being tested?: Pembrolizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 44 participants
Where: 2 sitesin 2 countries
Study dates: 3 Jul 2020to 1 Dec 2026
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
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed HER2-negative breast cancer (infiltrating ductal or lobular breast carcinoma) with measurable metastatic disease.
Must have received at least one but not more than three (3) prior lines of palliative chemotherapy for metastatic breast cancer.
Have received at least one line of hormonal therapy in the metastatic setting, for patients with ER+ (positive) breast cancer.
Documented germline APOBEC3B mutation (i.e. germline deletion).
Can provide archival tumour tissue sample or willing to provide tissues from a newly obtained core or excisional biopsy of a tumour lesion not previously irradiated. Note: Formalin-fixed, paraffin embedded (FFPE) tissue blocks or slides allowed (10 unstained slides are needed);
Have measurable disease based on RECIST 1.1 as determined by local radiology review. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

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Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (assessed within 10 days prior to the start of study treatment).
Have life expectancy of at least 3 months.
Have adequate organ function, within 10 days prior to the start of study treatment, as defined in the following:
Absolute neutrophil count (ANC) ≥ 1,500/µl.
Hemoglobin (Hb) ≥ 9 g/dL or 5.6mmol/La.
Platelets > 100,000/µl.
Creatinine ≤ 1.5 times ULN.
ALT (SGPT) and AST (SGOT) ≤ 2.5 times the ULN (≤5 times for patients with liver metastases).
Total bilirubin ≤ 1.5 mg/dL.
LDH ≤2.0 times the ULNWomen of child-bearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study treatment.
Women of child-bearing potential prepared to use adequate contraceptive measures if sexually active for the course of the study through 120 days after the last dose of treatment.
Have signed informed consent and able to comply with scheduled visits, treatment plan and other study procedures.

Who cannot join

Has HER2-positive breast cancer (FISH/CISH confirmed status, or 3+ IHC status)
Has use of any investigational agent or participation in another therapeutic clinical trial concurrently or in the 30 days prior to inclusion.
Has not recovered (e.g. to ≤Grade 1 or to baseline) from AEs due to a previously administrated therapy. Note: Participants with ≤Grade 2 neuropathy may be eligible.
Has an active autoimmune disease that has required systemic treatment in the past 2 years (e.g. with the use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systematic treatment.
Has a diagnosis of immunodeficiency or is receiving systematic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study treatment.
Has a concurrently active second malignancy, other than adequately treated non-melanoma skin cancers, in situ melanoma or in situ cervical cancer. Subjects with other non-mammary malignancies must have been disease-free for at least 5 years.

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Has known active CNS metastases and/or carcinomatous meningitis. Previously treated brain metastases may participate provided these remain stable.
Has received prior therapy with an anti-PD1, anti-PDL1 or anti-PDL2 agent or with an agent directed to another co-inhibitory T cell receptor (such as CTLA-4, OX-40, and CD137) or has previously participated in pembrolizumab clinical studies.
Patient who has received a live vaccine within 30 days of the first dose of study drug.
Known hypersensitive or allergy to pembrolizumab and any of its components.
Patient who is pregnant or breastfeeding.
Patient with an expected life expectancy of less than 3 months.
History of significant comorbidities that, in the opinion of the investigator, may interfere with the conduct of the study, the evaluation of response, or with informed consent.
Active uncontrolled infection at the time of inclusion.
Has a history of class II-IV congestive heart failure or myocardial infraction.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of this study
Has evidence of active pneumonitis, or non-infectious pneumonitis requiring treatment with steroids.
Has a known history of Human Immunodeficiency Virus (HIV).
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.

Trial locations and contacts

2 sites in 2 countries.

Country

City, postcode or hospital

2 sites in 2 countries

Malaysia1 site

University Malaya Medical Centre
Kuala Lumpur, Kuala Lumpur, 59100

Other trials in Malaysia

Singapore1 site

National University Hospital
Singapore, 119228

Other trials in Singapore

About this study

Official title: Phase II, Single Arm, Open Label, Simon Two-Stage Study of Pembrolizumab in Metastatic HER2-negative Breast Cancer Patients: Evaluation of Impact of Germline Variants in APOBEC3B

This is an open label investigator initiated Phase II study of single agent pembrolizumab (Keytruda) in metastatic HER2-receptive negative breast cancer patients with germline deletion in the cytosine deaminase (APOBEC3B) gene. Approximately 44 subjects from Malaysia and Singapore will be enrolled in this study to examine the efficacy of pembrolizumab when given 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations (2 years). This study will be conducted in conformance with Good Clinical Practices. Specific procedures to be performed during the trial, as well as their prescribed times and associated visit windows, are outlined in the Trial Flow Chart.

Read the detailed description

This is an open label investigator initiated Phase II study of single agent pembrolizumab (Keytruda®) in metastatic HER2-receptive negative breast cancer patients with germline deletion in the cytosine deaminase (APOBEC3B) gene. Approximately 44 subjects will be enrolled in this study to examine the efficacy of pembrolizumab when given 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations (2 years). ER+ patients need to have failed at least one line of prior hormonal treatment. All patients need to have failed at least one line, but no more than 3 lines, of prior chemotherapy in the metastatic setting.

Disease status will be followed by imaging studies at 9 weekly interval (± 7 days) during the first year, independent of any treatment delays, and every 12 weeks (±7 days) after the first year, until disease progression, start of non-study treatment, withdrawal of consent to study participation, death or end of the study. RECIST 1.1 will be used as the primary efficacy endpoint of response rate. Safety will be monitored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

Study treatment will continue until any of the following occurs:

Disease progression, as defined by Response Evaluation Criteria in Solid Tumour (RECIST version 1.1) (when progressive disease [PD] is confirmed, subject may be further followed up using consensus guideline of modified RECIST 1.1 [iRECIST] criteria);
Unacceptable toxicity;
Intercurrent illness that necessitates discontinuation of study treatment;
Investigator's decision to withdraw the subject,
Pregnancy;
Non-compliance with study treatment or procedure requirements;
Withdrawal of consent to treatment;
Death;
End of the study;
Other administrative reasons requiring cessation of study treatment.

This study will be conducted in conformance with Good Clinical Practices.

Specific procedures to be performed during the trial, as well as their prescribed times and associated visit windows, are outlined in the Trial Flow Chart - Section 6.0. Details of each procedure are provided in Section 7.0 - Trial Procedures.

Subject will be given a pre-screening inform consent form to participate in the genetic testing to determine their APOBEC3B germline mutation status.

Subject with confirmed APOBEC3B germline mutation will be given another inform consent form to participate in the main study.

The primary objective of the trial is to determine the efficacy of pembrolizumab in metastatic HER2-negative breast cancer subjects with APOBEC3B germline deletion polymorphism. Secondary objectives include progression-free survival (PFS), overall survival (OS) and response duration in this subject populations. The relationships of the germline variation, the associated molecular signatures, as well as other potential prognostic biomarkers with the study treatment will be explored as the exploratory objectives.

Conditions: HER2-Negative Breast Cancer
Being tested: Pembrolizumab
Keywords: Germline APOBEC3B mutation, Pembrolizumab

What participants receive

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

PembrolizumabDrug
Also called Keytruda
The planned dose of pembrolizumab for this study is 200 mg every 3 weeks (Q3W). Based on the totality of data generated in the Keytruda® development program, 200 mg Q3W is the appropriate dose of pembrolizumab for adults across all indications and regardless of tumour type.
All participants who off study treatment with stable disease (SD) or better may be eligible for up to an additional 17 cycles (approximately 1 year) of pembrolizumab treatment if they progress after stopping study treatment from the initial treatment phase. This retreatment is termed the Second Course Phase of this study and is only available if the study remains open and the participant met certain criteria as stated in the protocol.

Study groups in NCT03989089
Study group	Role	What they receive
Pembrolizumab single agent	Experimental	Pembrolizumab 200 mg will be given intravenously every 3 weeks , on Day 1 on each 3 week cycle. Pembrolizumab can be given up to 35 adminstration (2 years). Receives: Drug: Pembrolizumab

What is being measured

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

Overall response rate (ORR)
To determine the overall response rate (ORR) to the pembrolizumab treatment in metastatic HER2-negative breast cancer patients with germline APOBEC3B deletion polymorphisms using RECIST 1.1.
Measured: Up to 4 years

Secondary outcomes (3)

Progression free survival (PFS)
To estimate the progression free survival (PFS) to the pembrolizumab treatment in metastatic HER2-negative breast cancer patients with germline APOBEC3B deletion polymorphisms.
Measured: Up to 4 years
Overall survival
To estimate overall survival (OS) to the pembrolizumab treatment in metastatic HER2-negative breast cancer patients with germline APOBEC3B deletion polymorphisms.
Measured: Up to 4 years
Disease control rate
To estimate the disease control rate (DCR) i.e. complete response (CR), partial response (PR) or stable disease (SD) to the pembrolizumab treatment in metastatic HER2-negative breast cancer patients with germline APOBEC3B deletion polymorphism.
Measured: Up to 4 years

Timeline

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

3 Jul 20201 Dec 2026

First posted18 Jun 2019
Study start3 Jul 2020
Primary completion1 Dec 2025 (estimated)
Study completion1 Dec 2026 (estimated)

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 HER2-Negative Breast CancerStudies of the same condition, open and under way.
More trials run by University of MalayaThe 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
Model description: Single group assignment
Masking: None (open label)
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03989089
Sponsor's protocol ID: IIT-UM2018001
Status last verified: Dec 2024
First submitted: 25 Feb 2019
Last updated: 18 Dec 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Ho GF, Lee SC, Bustam AZ, Alip A, Abdul Satar NF, Saad M, Malik RA, Lim SE, Ow SGW, Wong A, Chong WQ, Ang YLE, Lee AWY, Hasan SN, Tuan Zaid N, Law KB, Toh YY, Tan HC, Selvam B, Lim J, Pan JW, Teo SH. Pembrolizumab monotherapy for previously treated metastatic HER2-negative breast cancer with germline APOBEC3B deletion: results of the phase II AUROR study. Lancet Reg Health West Pac. 2025 Jul 13;60:101637. doi: 10.1016/j.lanwpc.2025.101637. eCollection 2025 Jul.
PubMed 40697533

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
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RecruitingObservational study
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All HER2-Negative Breast Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase II, Single Arm, Open Label, Simon Two-Stage Study of Pembrolizumab in Metastatic HER2-negative Breast Cancer Patients: Evaluation of Impact of Germline Variants in APOBEC3B
ClinicalTrials.gov ID: NCT03989089
Acronym / sponsor ID: IIT-UM2018001
Conditions: HER2-Negative Breast Cancer
Keywords: Germline APOBEC3B mutation, Pembrolizumab
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 44 participants (actual)
Lead sponsor: University of MalayaUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC, National University Hospital, Singapore, Cancer Research Malaysia
Study start: 3 Jul 2020 (actual)
Primary completion: 1 Dec 2025 (estimated)
Study completion: 1 Dec 2026 (estimated)
First posted: 18 Jun 2019 (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.

Detailed description

Study treatment will continue until any of the following occurs:

Disease progression, as defined by Response Evaluation Criteria in Solid Tumour (RECIST version 1.1) (when progressive disease [PD] is confirmed, subject may be further followed up using consensus guideline of modified RECIST 1.1 [iRECIST] criteria);
Unacceptable toxicity;
Intercurrent illness that necessitates discontinuation of study treatment;
Investigator's decision to withdraw the subject,
Pregnancy;
Non-compliance with study treatment or procedure requirements;
Withdrawal of consent to treatment;
Death;
End of the study;
Other administrative reasons requiring cessation of study treatment.

This study will be conducted in conformance with Good Clinical Practices.

Subject will be given a pre-screening inform consent form to participate in the genetic testing to determine their APOBEC3B germline mutation status.

Subject with confirmed APOBEC3B germline mutation will be given another inform consent form to participate in the main study.

Study design

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

Arm	Type	Receives
Pembrolizumab single agent	Experimental	Drug: PembrolizumabPembrolizumab 200 mg will be given intravenously every 3 weeks , on Day 1 on each 3 week cycle. Pembrolizumab can be given up to 35 adminstration (2 years).

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (18 listed)

Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed HER2-negative breast cancer (infiltrating ductal or lobular breast carcinoma) with measurable metastatic disease.
Must have received at least one but not more than three (3) prior lines of palliative chemotherapy for metastatic breast cancer.
Have received at least one line of hormonal therapy in the metastatic setting, for patients with ER+ (positive) breast cancer.
Documented germline APOBEC3B mutation (i.e. germline deletion).
Can provide archival tumour tissue sample or willing to provide tissues from a newly obtained core or excisional biopsy of a tumour lesion not previously irradiated. Note: Formalin-fixed, paraffin embedded (FFPE) tissue blocks or slides allowed (10 unstained slides are needed);

Key exclusion criteria (19 listed)

Has HER2-positive breast cancer (FISH/CISH confirmed status, or 3+ IHC status)
Has use of any investigational agent or participation in another therapeutic clinical trial concurrently or in the 30 days prior to inclusion.
Has not recovered (e.g. to ≤Grade 1 or to baseline) from AEs due to a previously administrated therapy. Note: Participants with ≤Grade 2 neuropathy may be eligible.
Has an active autoimmune disease that has required systemic treatment in the past 2 years (e.g. with the use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systematic treatment.
Has a diagnosis of immunodeficiency or is receiving systematic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study treatment.

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
PembrolizumabAlso: KeytrudaThe planned dose of pembrolizumab for this study is 200 mg every 3 weeks (Q3W). Based on the totality of data generated in the Keytruda® development program, 200 mg Q3W is the appropriate dose of pembrolizumab for adults across all indications and regardless of tumour type. All participants who off study treatment with stable disease (SD) or better may be eligible for up to an additional 17 cycles (approximately 1 year) of pembrolizumab treatment if they progress after stopping study treatment from the initial treatment phase. This retreatment is termed the Second Course Phase of this study and is only available if the study remains open and the participant met certain criteria as stated in the protocol.	Drug	Pembrolizumab single agent

Primary outcome

Overall response rate (ORR)
Time frame: Up to 4 years
To determine the overall response rate (ORR) to the pembrolizumab treatment in metastatic HER2-negative breast cancer patients with germline APOBEC3B deletion polymorphisms using RECIST 1.1.

3 secondary outcomes

Progression free survival (PFS)
Time frame: Up to 4 years
Overall survival
Time frame: Up to 4 years
Disease control rate
Time frame: Up to 4 years

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 18 Dec 2024.
Derived from this study: PubMed 40697533Ho GF, Lee SC, Bustam AZ, Alip A, Abdul Satar NF, Saad M, Malik RA, Lim SE, Ow SGW, Wong A, Chong WQ, Ang YLE, Lee AWY, Hasan SN, Tuan Zaid N, Law KB, Toh YY, Tan HC, Selvam B, Lim J, Pan JW, Teo SH. Pembrolizumab monotherapy for previously treated metastatic HER2-negative breast cancer with germline APOBEC3B deletion: results of the phase II AUROR study. Lancet Reg Health West Pac. 2025 Jul 13;60:101637. doi: 10.1016/j.lanwpc.2025.101637. eCollection 2025 Jul.

Related trials for HER2-Negative Breast Cancer

RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Recruiting
Short-Term Reduced Dietary Protein in ER+/HER2- Breast Cancer Patients During Neoadjuvant Chemotherapy
Breast Cancer, Hormone Receptor Positive / HER2-negative Breast Cancer
Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
RecruitingPhase 3
Adding an Immunotherapy Drug, MEDI4736 (Durvalumab), to the Usual Chemotherapy Treatment (Paclitaxel, Cyclophosphamide, and Doxorubicin) for Stage II-III Breast Cancer
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8
RecruitingObservational study
A Study to Assess Treatment Patterns and Treatment Adherence in Early HER2-positive Breast Cancer Participants After Treatment Decentralization
Early-stage HER2+ Breast Cancer

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.

Adlinda Alip, FRCR principal investigator

University of Malaya

2 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab in people with HER2-Negative Breast Cancer, run by University of Malaya at 2 sites in 2 countries.

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 18 inclusion and 19 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 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Malaysia, 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?

Overall response rate (ORR) (time frame: Up to 4 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 NCT03989089, 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 18 Dec 2024.