Phase II trial of pembrolizumab and paclitaxel in hormone receptor-positive, hyperMUTATted metastatic breast cancer Identified by whole exOme sequeNcing (‘MUTATION2’)
- Conditions
- Neoplasms
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Female
- Target Recruitment
- 52
1. Histologically or cytologically confirmed premenopausal or postmenopausal hormone receptor-positive stage 4 breast cancer patients.
*Definition of hormone receptor positivity: Immunochemical staining using tumor samples, when the degree of nuclear staining of tumor cells in ER or PR is between 1 and 100% (ASCO/CAP guideline 2020)
2. Patients who have given written informed consent for this clinical study.
3. Patients who did not receive systemic cytotoxic chemotherapy in metastatic state. Hormone therapy and anti-HER2 targeted therapy are not limited.
4. Patients over 19 years of age as of the date of written informed consent.
5. The criteria for hypermutated are satisfied based on whole exome sequencing.
* Criteria for overmutation: The number of nonsynonymous mutations is initially set as 70 or more, and is applied based on the top 20% or higher through interim analysis for every 30 cases. That is, the standard may be changed every about 30 cases.
6. Patients with metastatic tumors that can be biopsied for complete exome sequencing. Biopsy of breast or axillary lymph node tumors is also allowed for patients with local recurrence after surgery or in stage 4 from diagnosis.
7. Patients with one or more measurable lesions based on RECIST v1.1. Tissues that have undergone biopsy are considered measurable lesions if not resected.
8. Patients whose disease progression has been confirmed since the most recent treatment (not applicable in the prescreening stage, ie, tissue biopsy is possible while maintaining the existing treatment).
9. Patients with an expected life span of 12 weeks or more.
10. ECOG is 0 to 1.
11. The laboratory test conducted within 10 days prior to the start of treatment meets the criteria described in the protocol.
12. In the case of female patients of childbearing potential, a urine test or serum pregnancy test confirmed negative pregnancy reaction within 72 hours prior to the first administration of the test drug. If the urine test is positive or negative and it is difficult to confirm, a serum pregnancy test is required.
13. For female patients of childbearing potential, willingness to use the appropriate method of contraception described in the protocol by day 180 after the last dose of the investigational drug.
*If abstinence is the patient's personal routine and the preferred method of contraception, that method of contraception is also acceptable.
1. Women of childbearing potential who have a positive urine pregnancy test within 72 hours prior to the first administration of the test treatment. If a urine test cannot confirm negative, a serum pregnancy test should be performed. In this case, if the serum pregnancy test result is positive, the participant must be excluded from participation in the test.
2. Has a history of receiving treatment with drugs targeting anti-PD-1, anti-PD-L1, anti-PD-L2 agents, or other stimulating or co-inhibiting T-cell receptors (eg CTLA-4, OX 40, CD137).
3. In the case of receiving prior systemic chemotherapy including study drugs within 4 weeks prior to randomization [In the case of kinase inhibitors or other short half-life drugs, less than 5 times the half-life before randomization has passed]
4. Previous radiation therapy within 2 weeks of starting treatment. Participants must recover from all radiation-related toxicity, do not need corticosteroids, and must not have had radiation pneumonia. A 1-week withdrawal period is permitted for palliative radiation (less than 2 weeks of radiation treatment) for non-CNS diseases.
5. Received live vaccine within 30 days prior to the first administration of the investigational drug.
-Note: Because seasonal influenza vaccines are generally inactivated flu vaccines, clinical participation is permitted. However, intranasal influenza vaccines (e.g. Flu-Mist®) are herbal poisoned vaccines and are not allowed to participate in clinical trials.
6. If there is a currently participating clinical study, participated in a clinical trial for an investigational drug within 4 weeks prior to the first administration of the investigational drug, and received trial treatment or used an investigational medical device.
-Note: Patients currently participating in observational studies can enroll in this study if 4 weeks have passed since the last drug administration.
7. Has been diagnosed with immunodeficiency or has been chronically receiving systemic steroid therapy (in excess of a dose equivalent to 10 mg per day of prednisone) or other immunosuppressive therapy in any form within 7 days prior to first administration of the test treatment.
8. Other invasive malignancies are known that are ongoing or require active treatment within the past 2 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, epidermal bladder cancer, or in situ cervical carcinoma are not eligible for curative treatment.
9. Active central nervous system (CNS) metastases and/or carcinoma meningitis are excluded from clinical trials. Patients treated for past brain metastasis are stable (if there is no progression of the disease on imaging for at least 4 weeks prior to the first administration of the clinical trial drug, and neurological symptoms have recovered to the baseline level), new metastasis to the brain, and If there is no enlargement of metastases and no steroids have been used for at least 7 days prior to clinical treatment, they can participate in clinical trials. Carcinoma meningitis is excluded from this study regardless of its clinical stability.
10. Previous history of hypersensitivity to Pembrolizumab or its excipients (grade 3 or higher)
11. In case of hypersensitivity to Paclitaxel or its excipients (grade 2 or higher peripheral neurosis) or contraindications to Paclitaxel
12. Active autoimmune diseases requiring systemic treatment within the past 2 years (eg, use of disease modula
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method