M7824 and Eribulin Mesylate in Treating Participants With Metastatic Triple Negative Breast Cancer

Study Drug Administration:

Every cycle is 42 days (6 weeks).

Participant will receive M7824 by vein over about 1 hour on Days 1, 15, and 29 of each cycle.
Participant will stay in the clinic for about 2 hours after the infusion so the study staff
can watch participant for any side effects. If participant cannot tolerate the study drug,
participant's dose may be lowered or stopped.

Participant will receive eribulin by vein over about 2-5 minutes on Days 1, 8, 22, and 29 of
each cycle.

Length of Study:

Participant may receive M7824 and eribulin for as long as the study doctor thinks it is in
participant's best interest. Participant will no longer be able to take the study drugs if
the disease gets worse, if intolerable side effects occur, or if participant is unable to
follow study directions.

If the disease appears to get worse, participation in this study will be over.

Study Visits:

On Day 1 of Cycle 1:

- Participant will have a physical exam.

- Blood (about 4½ tablespoons) will be drawn for routine (including thyroid function),
biomarker (including genetic biomarker), and immune system testing.

- Urine will be collected for routine tests.

- Blood (about 1 teaspoon) will be drawn for antibody testing. Antibodies are created by
the immune system and may attack foreign cells or substances, such as the study drugs.

- Blood (about 1 teaspoon) will be drawn for pharmacokinetic (PK) testing before and after
treatment. PK testing measures the amount of study drug in the body at different time
points.

- Participant will have an EKG.

- If participant can become pregnant, blood (about 1 teaspoon) or urine will be collected
for pregnancy test.

On Day 8 of Cycle 1:

- Participant will have a physical exam.

- Blood (about 4½ tablespoons) will be drawn for routine, biomarker (including genetic
biomarker), and immune system testing.

On Day 15 of Cycle 1:

- Participant will have a physical exam.

- Blood (about 4½ tablespoons) will be drawn for routine (including thyroid function),
biomarker (including genetic biomarker), and immune system testing.

- Blood (about 1 teaspoon) will be drawn for PK testing before treatment

On Day 29 of Cycle 1:

- Participant will have a physical exam.

- Blood (about 4½ tablespoons) will be drawn for routine (including thyroid function),
biomarker (including genetic biomarker), and immune system testing.

On Day 36 of Cycle 1:

°Participant will have a physical exam.

On Day 1 of Cycles 2 and beyond:

- Participant will have a physical exam.

- Blood (about 4½ tablespoons) will be drawn for routine (including thyroid function),
biomarker (including genetic biomarker), and immune system testing.

- Urine will be collected for routine tests.

- Participant will have a tumor biopsy to check the status of the disease and for immune
system and biomarker testing (Cycle 3 only).

- During Cycles 2 and 3 blood (about 1 teaspoon) will be drawn for antibody testing.

- During Cycle 2 only, blood (about 1 teaspoon) will be drawn for PK testing before and
after treatment.

- During Cycle 3 only, blood (about 1 teaspoon) will be drawn for PK testing before
treatment.

On Day 15 and 29 of cycles 2 and beyond:

°Blood (about 4½ tablespoons) will be drawn for routine (including thyroid function),
biomarker (including genetic biomarker), and immune system testing.

On Day 22 of all cycles:

- Participant will have a physical exam.

- Blood (about 4½ tablespoons) will be drawn for routine and immune system testing.

Every 6 weeks, participant will have a CT scan.

If the disease has gotten worse:

- Participant will have a physical exam.

- Participant will have a biopsy to determine if the tumor has grown due to activity in
the immune system.

- Participant will also have blood (about 4½ tablespoons) collected for routine tests, to
check clotting, thyroid, liver and kidney function, and biomarker testing.

- Participant will have blood (about 1 teaspoon) collected for antibody testing.

- Participant will also have a CT scan.

90 Days after End of Treatment:

- Participant will be asked if participant has any side effects either at participant's
appointment or by telephone or email. If participant returns to MD Anderson for
participant's appointment, blood (about 2 teaspoons) will be collected for antibody
testing and PK testing.

Inclusion Criteria:

1. Signed written informed consent.

2. Histologically confirmed metastatic triple negative breast cancer with measureable
disease by RECIST 1.1 criteria HR defined as positive for the purposes of this study,
if expression of estrogen receptor (ER) and/or progesterone receptor (PR) expression
is greater than 10% by immunohistochemistry (IHC) and HER2 negative or non-amplified
is determined by the current ASCO-CAP criteria, which are as follows: HER2 testing by
IHC as 0 or 1+. If HER2 is 2+, ISH (in situ hybridization) must be performed.

3. ECOG performance status of 0-1.

4. Baseline MUGA or echocardiogram scans with LVEF of > 50%.

5. Patient must have adequate organ function as determined by the following lab values:
ANC =/> 1500 cells/µL -WBC counts > 2500/µL - Lymphocyte count =/> 300/µL Platelet
count =/> 100,000/µL Hemoglobin =/> 9.0 g/dL -Hepatic impairment Child-Pugh bilirubin disease who have serum indirect bilirubin level dose modification necessary in patients with hepatic insufficiency according to USPI -
AST and ALT involvement: AST and/or ALT following exception: Patients with documented liver involvement or bone metastases:
alkaline phosphatase 50 mL/min on the basis of
the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) x (weight in
kg) x (0.85 if female) 72 x (serum creatinine in mg/dL)

6. INR and aPTT therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as
low-molecular-weight heparin or warfarin) should be on a stable dose.

7. Men or women 18 years of age or older.

8. Women of childbearing potential must be using an adequate method of contraception to
avoid pregnancy during the study and for at least 4 months after the last dose of
study drugs in such a manner that the risk of pregnancy is minimized. Men on study
also must be using contraception. Women of childbearing potential (WOCBP) are women
who have not been postmenopausal greater than 1 year or undergone a hysterectomy or
bilateral oophorectomy.

9. Negative serum or urine pregnancy test for women within 72 hours of receiving the
first dose of the study medication for women of childbearing potential.

10. Has received no more than 5 previous lines of chemotherapy.

Exclusion Criteria:

1. Women who are pregnant or breast-feeding.

2. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or
anti- Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including
ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation
or checkpoint pathways) for metastatic breast cancer-or- if patient has had prior
immune-oncology therapies in the neoadjuvant or adjuvant setting within the past 12
months.

3. Has had major surgery within 21 days before Cycle 1, Day 1.

4. Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).

5. Myocardial infarction within 6 months before starting therapy, symptomatic congestive
heart failure (New York Heart Association > class II), unstable angina, or unstable
cardiac arrhythmia requiring medication.

6. Serious intercurrent infections or non-malignant medical illness that are uncontrolled
or the control of which may be jeopardized by this therapy.

7. Psychiatric disorders or other conditions rendering the subject incapable of complying
with the requirements of the protocols.

8. History or risk of autoimmune disease, including but not limited to systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's
syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune
thyroid disease, vasculitis, or glomerulonephritis.

9. Patients with a history of autoimmune hypothyroidism (such as atrophic thyroiditis) on
a stable dose of thyroid replacement hormone may be eligible.

10. Patients with uncontrolled Type 1 diabetes mellitus. If on a stable insulin regimen
may be eligible, after discussion with Principal Investigator.

11. Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis would be
excluded) are permitted provided that they meet the following conditions: Patients
with psoriasis must have a baseline ophthalmologic exam to rule out ocular
manifestations Rash must cover less than 10% of body surface area (BSA) Disease is
well controlled at baseline and only requiring low potency topical steroids (e.g.,
hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%,
alclometasone dipropionate 0.05%) No acute exacerbations of underlying condition
within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA],
methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or
oral steroids)

12. Patients with HIV-1 may be eligible if they meet the following conditions: -CD4 cell
count > 350 cells/mm3 obtained within 90 days prior to study start -Plasma HIV-1 RNA
below detected limit obtained by FDA-approved assays for > 2 years on cART -Plasma
HIV-1 RNA level of less than 40 copies/mL obtained by the Abbott m2000 assay or less
than 20 copies/mL by Roche Taqman v2.0 assay within 90 days prior to study start
-Plasma HIV-1 RNA greater than or equal to 0.4 copies/mL by single copy assay within
120 days prior to entry -Receiving a stable cART regimen containing at least 3 agents
(not including ritonavir if less than a 200 mg total daily dose) with no change in the
components of antiretroviral therapy for at least 90 days prior to study entry

13. Patients with prior allogeneic stem cell or solid organ transplantation.

14. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

15. Patients with known active hepatitis B (defined as having a positive hepatitis B
surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past
hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a
negative HBsAg test and a positive antibody to hepatitis B core antigen [anti HBc]
antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody
are eligible only if polymerase chain reaction is negative for HCV RNA.

16. Known active tuberculosis

17. Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or
anticipation that such a live, attenuated vaccine will be required during the study.
Influenza vaccination should be given during influenza season only (approximately
October to March). Patients must not receive live, attenuated influenza vaccine (e.g.,
FluMist) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.

18. Treatment with systemic immunostimulatory agents (including but not limited to
interferons or IL-2) within 4 weeks or five half-lives of the drug, whichever is
shorter, from Cycle 1 Day 1.

19. Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including but not limited to prednisone, dexamethasone, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents)
within 1 week prior to Cycle 1 Day 1, or anticipated requirement for systemic
immunosuppressive medications during the trial. Patients who have received acute, low
dose, systemic immunosuppressant medications (e.g., dexamethasone prior to the
anthracycline-based chemotherapy for nausea) may be enrolled in the study. The use of
inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.

20. Concurrent disease or condition that would interfere with study participation or
safety, such as any of the following: Active, clinically significant infection either
grade > 2 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse
Events (CTCAE) v4.03 or requiring the use of parenteral anti-microbial agents within
14 days before Day 1 of study drug -Clinically significant bleeding diathesis or
coagulopathy, including known platelet function disorders Non-healing wound, ulcer, or
bone fracture

21. Known hypersensitivity to any of the components of M7824 or eribulin

22. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins.

23. Subjects with active central nervous system (CNS) metastases causing clinical symptoms
or metastases that require therapeutic intervention, including leptomeningeal disease,
are excluded. Subjects with a history of treated CNS metastases (by surgery or
radiation therapy) are not eligible unless they have fully recovered from treatment,
demonstrated no progression for at least 2 months, and do not require continued
steroid therapy.