Pilot Study of Paclitaxel Plus Pembrolizumab in Metastatic HER2-Negative Breast Cancer

Inclusion Criteria

• •Subjects must meet all of the following criteria:
• •1. Histologically or cytological confirmed diagnosis of HER2-negative metastatic breast cancer or locally advanced disease not amenable to resection.
• •* Available ER and PR status from tumor sample with either hormone receptor positive or negative tumor(s).
• •2. Measurable disease by RECIST 1.1, or evaluable bone disease, i.e., bone lesions that are lytic or mixed (i.e. lytic + sclerotic) in the absence of measurable lesion. Refer to section 11 for the evaluation of measurable disease.
• •3. Male or female age ≥18 years.
• •4. ECOG performance status 0, 1 or 2.
• •5. Must have normal organ and marrow function as defined below:
• •* Hematologic - Absolute neutrophil count ≥1,500/mcL
• •\- Platelets ≥75,000/mcL
• •\- Hemoglobin ≥ 9 g/dL
• •* Renal
• •* Creatinine ≤ 1.5X ULN or
• •* Measured or calculated creatinine clearance (CrCl) ≥ 30 mL/min for subject with creatinine levels \> 1.5X ULN \[CrCl should be calculated per institutional standard; GFR can also be used in place of creatinine or CrCl\]
• •* Hepatic
• •* Total bilirubin ≤1.5X ULN or for subjects with total bilirubin levels \>1.5X ULN, direct bilirubin ≤ULN
• •* AST(SGOT)/ALT(SGPT) ≤2.5X ULN
• •* Coagulation
• •6. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to receiving C1D1.
• •7. Female subjects of childbearing potential must be willing to use an adequate method of birth control as outlined in Section 8.1.10, be surgically sterile, or abstain from heterosexual activity for the course of the study and 120 days after the last dose of study therapy. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. Male subjects of reproductive potential should agree to use an adequate method of contraception starting with the first dose of study therapy and 120 days after the last dose of study therapy. Abstinence is acceptable if this is the established and preferred contraception for the subject.
• •8. Has completed the screening requirement of a core or punch biopsy of a tumor lesion per Section 5 (bone tissue not acceptable). Biopsy of the breast tumor or other regional areas is acceptable (i.e. lymph nodes, skin lesions).
• •* Subjects who are unable to meet the screening requirement of a tumor biopsy due to inaccessible tumor, subject safety concern, or bone-only disease may submit an archived tumor specimen from primary tumor or metastatic biopsy collected within 12 months from consent.
• •* Subjects who decline tumor biopsy may submit archived tumor specimen as specified above (within 12 months from consent) only after Sponsor-Investigator approval.
• •9. Ability to understand and the willingness to sign the written informed consent document.
• •9. History of known allergic reaction to paclitaxel
• •10. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might 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.
• •11. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. Pregnant women are excluded from this study because paclitaxel is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with paclitaxel, breastfeeding should be discontinued if the mother is treated with paclitaxel. These potential risks also apply to pembrolizumab being used in this study.
• •12. Has a known history of Human Immunodeficiency Virus (HIV) or known acquired immunodeficiency disorder (AIDS). HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with paclitaxel and pembrolizumab. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• •13. Has known active infection with hepatitis B or hepatitis C.
• •14. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• •o Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• •15. Has a known additional malignancy that progressed or required active treatment within the last 5 years.
• •o Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer.
• •16. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• •17. Has an active infection requiring systemic therapy.
• •18. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •19. Has received a live vaccine within 30 days of Cycle 1 Day 1 of study therapy. o 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.