| Eligibility |
Inclusion Criteria:
1. Male participants or female participants who are pre or postmenopausal women and at
least 19 years of age on the day of signing informed consent with histologically or
cytologically confirmed diagnosis of stage IV hormone receptor-positive breast cancer
will be enrolled in this study.
2. A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
2. a WOCBP must agree to use a contraception as detailed in Appendix 3 of this
protocol during the treatment period and for at least 120 days, corresponding to
time needed to eliminate any study treatments [e.g., 5 terminal half-lives for
pembrolizumab and paclitaxel (52.7 hours)] after the last dose of study
treatment.
3. No prior systemic cytotoxic chemotherapy in the metastatic setting. Lines of endocrine
or HER2-targeted therapy are not limited.
* No prior paclitaxel, except =12 months after last dose of chemotherapy for early
breast cancer (if chemotherapy given)
4. Criteria of hypermutation should be met.
*Criteria of hypermutation: 70 nonsynonymous mutations per tumor per exome as the
presumptive starting cut-off for upper 20% of mutation burden. we will revise cut-off
after enrolling every 30 patients. That is, the criteria of hypermutation will be
altered every 30 cases.
5. The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.
6. Have measurable disease based on RECIST 1.1. Lesions situated in a previously
irradiated area are considered measurable if progression has been demonstrated in such
lesions.
7. 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
8. Documented disease progression on the most recent therapy. This is not applicable
during prescreening phase. That is, tissue biopsy is possible while maintaining
existing treatment.
9. Life expectancy of > 12 weeks
10. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Evaluation of ECOG is to be performed within 7 days prior to the date of
allocation/randomization.
11. Have adequate organ function as defined in the following table(Table 2). Specimens
must be collected within 10 days prior to the start of study treatment.
Exclusion Criteria:
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
OX 40, CD137).
3. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks [could consider shorter interval for kinase inhibitors or other short
half-life drugs] prior to allocation.
4. Has received prior radiotherapy within 2 weeks of start of study intervention.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease.
5. Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
6. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study intervention.
- Note: Participants who have entered the follow-up phase of an investigational
study may participate as long as it has been 4 weeks after the last dose of the
previous investigational agent.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Has a history of a second malignancy, unless potentially curative treatment has been
completed with no evidence of malignancy for 2 years.
- Note: The time requirement does not apply to participants who underwent
successful definitive resection of basal cell carcinoma of the skin, squamous
cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer,
or other in-situ cancers
9. Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases (eg., whole brain radiation therapy, gamma-knife
surgery or brain tumor removal) may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study intervention.
10. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
11. Has hypersensitivity (=Grade 2 peripheral neuropathy) or contraindication to
paclitaxel or any of its excipients.
12. 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 and is allowed.
13. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
14. Has an active infection requiring systemic therapy.
15. Has a known history of Human Immunodeficiency Virus (HIV) infection: HIV-1 or HIV-2
antibody+ or HTLV-1 antibody+
16. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection.
1. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection
(defined as having a negative HBsAg test and a positive hepatitis B core antibody
[HBcAb] test, accompanied by a negative HBV DNA test) are eligible.
2. Patients positive for HCV antibody are eligible only if polymerase chain reaction
(PCR) is negative for HCV RNA.
17. Has a known history of active TB (Bacillus Tuberculosis).
18. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
19. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
20. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment.
21. Has had an allogenic tissue/solid organ transplant.
|
