Clinical Trials /

Pembrolizumab in Hormone Receptor-positive, hyperMUTATted Metastatic Breast Cancer Identified by Whole exOme sequeNcing ('MUTATION2')

NCT03492918

Description:

Abbreviated Title : Pembrolizumab in hypermutated breast cancer Trial Phase : II Clinical Indication : Hormone receptor-positive metastatic breast cancer Trial Type : Interventional Type of control : None Route of administration : Intravenous Trial Blinding : None Treatment Groups : Pembrolizumab Number of trial subjects : Approximately 150 patients will be prescreened with whole exome sequencing. Then 30 patients will be enrolled in the treatment phase. Estimated enrollment period : 12 months Estimated duration of trial : The sponsor estimates that the trial will require approximately 24 months from the time the first subject signs the informed consent until the last subject's last visit. Duration of Participation : 12 months Estimated average length of treatment per patient : 8 months

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Hormone Receptor-positive, hyperMUTATted Metastatic Breast Cancer Identified by Whole exOme sequeNcing ('MUTATION2')
  • Official Title: Phase II Trial of Pembrolizumab in Hormone Receptor-positive, hyperMUTATted Metastatic Breast Cancer Identified by Whole exOme sequeNcing ('MUTATION2')

Clinical Trial IDs

  • ORG STUDY ID: 2017-3465-001
  • NCT ID: NCT03492918

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
PembrolizumabKeytrudapembrolizumab group

Purpose

Abbreviated Title : Pembrolizumab in hypermutated breast cancer Trial Phase : II Clinical Indication : Hormone receptor-positive metastatic breast cancer Trial Type : Interventional Type of control : None Route of administration : Intravenous Trial Blinding : None Treatment Groups : Pembrolizumab Number of trial subjects : Approximately 150 patients will be prescreened with whole exome sequencing. Then 30 patients will be enrolled in the treatment phase. Estimated enrollment period : 12 months Estimated duration of trial : The sponsor estimates that the trial will require approximately 24 months from the time the first subject signs the informed consent until the last subject's last visit. Duration of Participation : 12 months Estimated average length of treatment per patient : 8 months

Trial Arms

NameTypeDescriptionInterventions
pembrolizumab groupExperimentalDrug:Pembrolizumab Dose/Potency:200 mg Dose Frequency:Q3W Route of Administration:IV infusion Regimen/Treatment Period:Day 1 of each 3 week cycle Use:Experimental
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Pre or postmenopausal women with stage IV hormone receptor-positive breast cancer by
             histological or cytological confirmation

          -  Be willing and able to provide written informed consent/assent for the trial

          -  Progression after 1 or more lines of any systemic therapy (endocrine, HER2-targeted or
             chemotherapy) in the metastatic setting

          -  Be over 19 years of age on day of signing informed consent

          -  70 or more nonsynonymous mutations per tumor by WES

          -  Subject who has biopsy-accessible tumor for WES. Biopsy on breast tumor or axillary
             nodes is acceptable if locoregional recurrence after primary surgery occurs or de novo
             stage IV breast cancer is diagnosed

          -  Have measurable disease based on RECIST 1.1. Biopsied tumor may be counted a
             measurable lesion if it is not excised

          -  Documented disease progression on the most recent therapy

          -  Life expectancy of > 12 weeks

          -  Have a performance status of 0 or 1 on the ECOG Performance Scale.

          -  Demonstrate adequate organ function as defined in Table 3, all screening labs should
             be performed within 10 days of treatment initiation.

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication. If
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required.

          -  Female subjects of childbearing potential (Section 5.5.2) must be willing to use an
             adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the
             course of the study through 120 days after the last dose of study medication.

        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
        for the subject.

        Exclusion Criteria:

          -  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 the first dose of treatment.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of 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 1 or who has not recovered (i.e., ≤ Grade 1 or at
             baseline) from adverse events due to a previously administered agent. Note: Subjects
             with irreversible toxicity that is not reasonably expected to be exacerbated by the
             investigational product may be included (e.g., ≤ Grade 2 neuropathy; hair loss, et
             al.), 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.
             However, malignancies that have been curatively treated >5 years prior to study entry
             can be included. Exceptionally, cervical cancer in-situ, basal cell carcinoma or
             squamous cell carcinoma of the skin, papillary thyroid carcinoma and superficial
             bladder tumors (T1a and Tis) can be included anytime after potentially curative
             treatment

          -  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 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 or any evidence of active, non-infectious pneumonitis.

          -  Evidence of interstitial lung disease.

          -  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.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 or HTLV-1
             antibodies).

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., anti-HCV
             antibody detected or HCV RNA [qualitative] detected).

          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change of objective response rate(ORR) by RECIST 1.1
Time Frame:Every 3 cycles (each cycle is 21 days)
Safety Issue:
Description:Objective response rate (ORR) based on RECIST 1.1 in hormone receptor-positive, hypermutated metastatic breast cancer identified by whole exome sequencing (WES) Hypothesis: Pembrolizumab in patients with hormone receptor-positive, hypermutated metastatic breast cancer identified by WES will result in clinically meaningful ORR based on RECIST 1.1

Secondary Outcome Measures

Measure:Clinical benefit rate(CBR) by RECIST 1.1
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Yonsei University

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