Effect of Pembrolizumab (Keytruda®) on Biomarkers in Early Breast Cancer.

NCT03197389 | Completed Early Phase 1 Results DMC

• 1 other identifier: MK 3475-318
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The study consists of 2 parts: a retrospective study, and a prospective clinical study with pembrolizumab (Keytruda®) (Phase 0).

1. 1.Retrospective study (S58910):
2. 2.Phase 0 study:

Conditions

Breast Cancer; Triple Negative Breast Cancer; Hormone Receptor Negative Neoplasm

Keywords

Biomarker

Outcome Measures

Primary Outcomes (1)

• PD-1 Expression

  PD-1 expression after a single dose of pembrolizumab. Immunohistochemical stains were performed on 5-μm thick sections using an automatic immunostainer (Bond Max Autostainer, Leica) according to the manufacturer's instructions. A monoclonal antibodie was used for PD1 (clone NAT105, Abcam). PD1 expression on sTIL was assessed semi quantitatively.

  2 years

Study Arms (6)

Cohort A1

OTHER

Cohort A1 will include patients with a triple negative breast tumor. Patients will be treated with one injection of Pembrolizumab (Keytruda®) administered intravenously at 200 mg 10 +/- 4 days before surgery.

Drug: Pembrolizumab

Cohort A2

OTHER

Cohort A2 will include patients with ER/PR negative and Her2 positive breast tumor. Patients will be treated with one injection of Pembrolizumab (Keytruda®) administered intravenously at 200 mg 10 +/- 4 days before surgery.

Drug: Pembrolizumab

Cohort B1

OTHER

Cohort B1 will include patients with a triple negative breast tumor who received neoadjuvant chemotherapy and who have clear signs of residual tumor on imaging after finishing neoadjuvant chemotherapy (i.e. on imaging estimated residual tumor size of at least 10 mm). Patients will be treated with one injection of Pembrolizumab (Keytruda®) administered intravenously at 200 mg 10 +/- 4 days before surgery.

Drug: Pembrolizumab

Cohort B2

OTHER

Cohort B2 will include patients with a ER/PR negative and Her2 positive breast tumor who received neoadjuvant chemotherapy and who have clear signs of residual tumor on imaging after finishing neoadjuvant chemotherapy (i.e. on imaging estimated residual tumor size of at least 10 mm). Patients will be treated with one injection of Pembrolizumab (Keytruda®) administered intravenously at 200 mg 10 +/- 4 days before surgery.

Drug: Pembrolizumab

Cohort A3

OTHER

Cohort A3 will include patients with ER positive breast tumor. Patients will be treated with one injection of Pembrolizumab (Keytruda®) administered intravenously at 200 mg 10 +/- 4 days before surgery.

Drug: Pembrolizumab

Cohort B3

OTHER

Cohort B3 will include patients with a ER positive breast tumor who received neoadjuvant chemotherapy and who have clear signs of residual tumor on imaging after finishing neoadjuvant chemotherapy (i.e. on imaging estimated residual tumor size of at least 10 mm). Patients will be treated with one injection of Pembrolizumab (Keytruda®) administered intravenously at 200 mg 10 +/- 4 days before surgery.

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Biological: humanized anti-PD-1 monoclonal antibody humanized anti-PD-1 monoclonal antibody is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2.

Also known as: Keytruda

Cohort A1; Cohort A2; Cohort A3; Cohort B1; Cohort B2; Cohort B3

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be 18 years of age on day of signing informed consent.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion if needed. Newly obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 0. Subjects for whom newly obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Have non-metastatic operable newly diagnosed primary invasive carcinoma of the breast that is:
• Histologically confirmed
• ER/PR negative or ER positive. ER/PR status will be evaluated with Allred score (semi-quantitative measurement) following ASCO CAP guidelines 2009.
• HER2 negative of positive. HER2 status will be evaluated using IHC followed by FISH with dual probe (ASCO CAP guidelines 2013).
• Primary tumor size greater than 1 cm, measured by any of clinical examination, mammography, ultrasound or magnetic resonance imaging
• Any clinical nodal status
• Have evaluable core biopsy for IHC
• Be willing to provide plasma/blood samples
• After neo-adjuvant chemotherapy (cohort B1 and B2) patients must have residual tumor \>1cm and must be willing to provide evaluable new tumor biopsy for IHC
• Demonstrate adequate organ function, all screening labs should be performed within 14 days of treatment initiation.
• Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of receiving the treatment dose.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to receiving the trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 0 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• 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.
• Has known 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.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

University Hospitals Leuven

Leuven, 3000, Belgium

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Prof. Dr. Ann Smeets
• Organization: University Hospitals Leuven

hanne.vos@uzleuven.be

003216340903

Study Officials

• Ann Smeets, Prof. Dr.

  Universitaire Ziekenhuizen KU Leuven

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2017
• First Posted: June 23, 2017
• Study Start: January 18, 2018
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: May 19, 2021
• Results First Posted: May 19, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)