Study of Pembrolizumab Plus Fulvestrant in Hormone Receptor Positive, HER-2 Negative Advanced/Metastatic Breast Cancer Patients

NCT03393845 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BTCRC-BRE16-042
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 5

Brief Summary

Pembrolizumab Plus Fulvestrant in Hormone Receptor Positive, HER-2 Negative Advanced/Metastatic Breast Cancer Patients

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Ratio (CBR)

  Clinical benefit ratio (CBR) is defined as the percentage of patients that achieve CR, PR, or stable disease for a minimum of four months. Patients will be evaluated for response by RECIST 1.1 and irRECIST.

  36 months

Secondary Outcomes (4)

• Safety profile of pembrolizumab plus fulvestrant

  36 months

• Progression free survival (PFS)

  36 months

• Durable response rate (DRR)

  36 months

• Overall Survival

  36 months

Study Arms (1)

Pembrolizumab + Fulvestrant

EXPERIMENTAL

Pembrolizumab 200m IV q3W + Fulvestrant. Loading dose 500mg IV IM q2W x3 followed by 500mg IM q4W

Drug: Pembrolizumab; Drug: Fulvestrant

Interventions

Pembrolizumab DRUG

Pembrolizumab 200mg IV, 21 day cycles

Also known as: Keytruda

Pembrolizumab + Fulvestrant

Fulvestrant DRUG

Fulvestrant, 500mg IM, Loading dose: C1 D1 \& 15. Thereafter, Q4 wks

Also known as: Faslodex

Pembrolizumab + Fulvestrant

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Men \[29\] and women ≥ 18 years of age at the time of informed consent. NOTE: Both pre- and post-menopausal women are eligible. Patients who are premenopausal should either undergo bilateral oophorectomy or receive ovarian suppression according to institutional standards. Male patients will be treated as premenopausal females and receive a GnRH agonist.
• ECOG Performance Status of 0 or 1 within 28 days prior to registration.
• Histologic or cytologic diagnosis of metastatic breast cancer.
• Has received no more than two lines of prior therapy for advanced non-resectable/metastatic disease. Prior lines can can be either chemotherapy or hormonal therapy. Prior or current fulvestrant is allowed. Combination therapy is considered as one regimen.
• Tumor is estrogen receptor positive (ER+) and/or (PR+), HER-2 negative (HER2-). ER and PR positivity is defined as \>1%. HER-2 negative is defined as by IHC (0, 1+) or FISH. HER2 positive test result includes: Single-probe average HER2 copy number ≥6.0 signals/cell; Dual-probe HER2/CEP17 ratio ≥2.0 with an average HER2; copy number ≥4.0 signals/cell; Dual-probe HER2/CEP17 ratio ≥2.0 with an average HER2copy number \<4.0 signals/cell; or Dual-probe HER2/CEP17 ratio \< 2.0 with an average HER2 copy number ≥6.0 signals/cell. Equivocal findings for IHC as 2+ should be reflexed to FISH. Equivocal results by FISH may be considered with approval from the Sponsor-Investigator.
• Measurable disease based on RECIST 1.1 within 28 days prior to registration. Except in patients with bone-only disease, in the absence of measurable disease, evaluable bone lesion is allowed. NOTE: Bone-only disease is the sole non-measurable disease site allowed and biopsy is required. Measurable disease is required in all other cases.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. NOTE: Subjects for whom newly-obtained fresh tissue samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor-Investigator.
• Normal cardiac function as determined by treating physician per institutional standards via echocardiogram (ECHO) performed within 28 days prior to registration.
• Prior chemotherapy must be completed at least 28 days prior to registration or at least 14 days prior to registration for targeted therapy.
• Prior hormonal therapy or radiation therapy must be completed at least 14 days prior to registration. If subject is currently receiving fulvestrant, it may continue without interruption as per standard of care.
• The subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline. 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 study registration, as determined by the enrolling physician.
• Demonstrate adequate organ function as defined in the table below; all screening labs will be performed within 28 days of study registration.
• Hematological
• Absolute Neutrophil Count (ANC): ≥ 1500/mm3

You may not qualify if:

• Is currently receiving an investigational agent or has received an investigational agent or used an investigational device within 28 days of study registration.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study registration. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a known history of active TB (Bacillus Tuberculosis). NOTE: TB testing is not required.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). NOTE: HIV testing is not required.
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• NOTE: Hepatitis B and Hepatitis C testing is not required.
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has received prior chemotherapy within 28 days prior to study registration or has received prior hormonal/targeted therapy within 14 days prior to study registration
• More than two lines of chemotherapy or more than two lines of hormonal therapy excludes participation.
• 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 known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has known history of non-infectious pneumonitis/interstitial lung disease that required steroids or has any evidence of active pneumonitis/interstitial lung disease.
• Has known history of, or any evidence of active interstitial lung disease, Class II-IV congestive heart failure, or myocardial infarction within 6 months from randomization.
• Active infection requiring systemic therapy.

Sponsors & Collaborators

• Nancy Chan, MD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

Michigan State University, Breslin Cancer Center

Lansing, Michigan, 48910, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

New York University Clinical Cancer Center

New York, New York, 10016, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab; Fulvestrant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Nancy Chan

  Rutgers Cancer Institute of New Jersey

  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: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 9, 2018
• Study Start: January 29, 2018
• Primary Completion: August 4, 2023
• Study Completion (Estimated): September 1, 2027
• Last Updated: January 2, 2026

Record last verified: 2025-12

Locations

US (5)