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

NCT03989089 | Active Not Recruiting Phase 2

• 1 other identifier: IIT-UM2018001
• Study Type: interventional
• Target: 44
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

HER2-Negative Breast Cancer

Keywords

Germline APOBEC3B mutation; Pembrolizumab

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 4 years

Secondary Outcomes (3)

• Progression free survival (PFS)

  Up to 4 years

• Overall survival

  Up to 4 years

• Disease control rate

  Up to 4 years

Study Arms (1)

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).

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

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.

Also known as: Keytruda

Pembrolizumab single agent

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Participant eligibility is based on gender identity.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• Has HER2-positive breast cancer (FISH/CISH confirmed status, or 3+ IHC status)
• 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.
• 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.
• 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.

Sponsors & Collaborators

• University of Malaya: lead
• Merck Sharp & Dohme LLC: collaborator
• National University Hospital, Singapore: collaborator
• Cancer Research Malaysia: collaborator

Study Sites (2)

University Malaya Medical Centre

Kuala Lumpur, Kuala Lumpur, 59100, Malaysia

Location

National University Hospital

Singapore, 119228, Singapore

Location

Related Publications (1)

• 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.

  PMID: 40697533 DERIVED

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Adlinda Alip, FRCR

  University of Malaya

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr

Model Details: Single group assignment

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: June 18, 2019
• Study Start: July 3, 2020
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 18, 2024

Record last verified: 2024-12

Locations

SG (1); MY (1)