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

Inclusion Criteria

Subjects must meet all of the following criteria:

• 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).
• For subjects with hormone receptor-positive, HER2-negative metastatic breast cancer, they are eligible if they have already received or been intolerant to at least two lines of endocrine therapies (including the adjuvant and/or metastatic setting), or are appropriate candidates for chemotherapy (i.e. large burden of visceral disease).
• 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.
• Male or female age ≥18 years.
• ECOG performance status 0, 1 or 2.
• 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
• PT and PTT ≤ 1.5X ULN; subjects receiving anticoagulant therapy are eligible if PT or PTT is within therapeutic range of intended use of anticoagulants per investigator discretion.
• INR ≤ 1.5; Patients receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation per investigator discretion.
• Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to receiving C1D1.
• 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.
• 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.
• Ability to understand and the willingness to sign the written informed consent document.

Exclusion Criteria

Subjects must not meet any of the following criteria:

• Prior chemotherapy within 3 weeks, prior targeted small molecule therapy or radiation therapy within 2 weeks, or prior anti-cancer monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks prior to Cycle 1 Day 1.
• Not recovered (i.e., ≤ Grade 1) from adverse events due to agents previously administered.

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