RACHEL1: Radiation and CHEckpoint bLockade Trial in Patients With Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer

Study Drug Administration:

There are 28 days in every cycle.

If you are found to be eligible to take part in this study, you will receive 1 of 2 dose
levels of MSB0011359C, based on when you join the study. The first 3 participants will
receive the higher of the 2 dose levels. Each new group (of 3) will receive the same dose
unless intolerable side effects are seen in a certain number of participants. If this occurs,
the next groups will receive the lower dose level of MSB0011359C. If intolerable side effects
are seen in a certain number of participants when using the lower dose, the study will be
stopped.

You will receive MSB0011359C by vein over about 1 hour every 14 days +/-3 days. You will be
watched for side effects for 2 hours after each infusion. Radiation therapy will start within
3 days after the second dose of MSB0011359C. Depending on the site of your disease, you will
receive radiation 1 time a day for 5 days or 10 days.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drug if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

If you cannot tolerate the study drug, your dose may be lowered or stopped.

Your participation on the study will be over 90 days after you receive the last dose of
MSB0011359C.

Pharmacokinetic (PK) Testing:

Blood (about 1 teaspoon) will be collected on Day 1 of Cycles 1 and 3, and before study drug
infusion in Cycles 2 and 6 for pharmacokinetic (PK) testing. They may also be tested at the
end of study visit. PK testing measures the amount of study drug in the body at different
time points. The samples will also be tested to learn how the drug has changed inside your
body. This will help the doctors decide if the daily dose of the study drug needs to be
increased, decreased, or remain at the current level.

Study Visits:

On Day 1 of Each Cycle:

- You will have a physical exam.

- Blood (about 14 teaspoons) will be drawn for routine tests and to measure your blood
sugar levels, blood clotting function, the amount of cholesterol in your blood, and your
thyroid, liver, and kidney functions.

- You will have an EKG to check your heart function.

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

On Day 56:

- You will have a physical exam.

- Blood (about 14 teaspoons) will be drawn for routine tests, to measure the amount of
cholesterol in your blood, and your liver and kidney functions.

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

- You will have a CT scan, a PET/CT scan, and/or an MRI to check the status of the
disease.

- You will have a tumor biopsy of 2 sites if possible (the site that received radiation
and a site that did not) on Day 56 or within 7 days of Day 56 for immune system and
biomarker testing, including genetic biomarkers.

End-of-Study Visit (EOT):

If the disease gets worse, you will have an end of study visit. At this visit you will have
the following tests:

- Blood (about 14 teaspoons) will be drawn for routine tests and to measure your blood
sugar levels, blood clotting function, the amount of cholesterol in your blood, and to
test your thyroid, liver, and kidney function.

- You will have a core biopsy to find out if the tumor has grown due to problems with your
immune system.

Inclusion Criteria:

1. Is willing and able to provide written informed consent for the trial and has signed
the appropriate written informed consent form, approved by the investigator's
Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the
performance of any trial activities.

2. Is Age >/= 18 years at time of study entry

3. ECOG Performance Status of 0-1

4. Highly effective contraception for both male and female subjects if the risk of
conception exists. Highly effective contraception must be used 30 days prior to first
trial administration, for the duration of trial treatment, and at least for 4 months
after stopping trial treatment (see Appendix 2 for further details). Should a woman
become pregnant or suspect she is pregnant while she or her partner is participating
in this trial, the treating physician should be informed immediately.

5. Has confirmed HR+ and HER2 negative breast cancer with known metastatic disease. HR
defined as positive if expression greater than 10% by immunohistochemistry (IHC). 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. HER2 is positive if: i. IHC 3+ based on circumferential membrane
staining that is a. complete, intense ii. ISH positive based on: a. Single-probe
average HER2 copy number =/>6.0 signals/cell. b. Dual-probe HER2/CEP17 ratio =/>2.0
with an average HER2 copy number =/>4.0 signals/cell c. Dual-probe HER2/CEP17 ratio
=/>2.0 with an average HER2 copy number <4.0 signals/cell d. Dual-probe HER2/CEP17
ratio < 2.0 with an average HER2 copy number =/>6.0 signals/cell

6. Has at least 2 identified sites of metastatic disease by imaging.

7. Has received no more than 5 previous lines of chemotherapy and has received at least
one line of therapy with an endocrine therapy or endocrine therapy combination.

8. Adequate hematological function, defined by white blood cell (WBC) count =/> 3 ×
10^9/L with ANC =/>1.5 × 10^9/L, lymphocyte count=/> 0.5 × 10^9/L, platelet count
=/>100 × 10^9/L, and Hgb =/>9 g/dL

9. Adequate hepatic function defined by a total bilirubin level of normal (ULN), an AST, level
10. International normalized ratio (INR) < 1.5

11. Adequate renal function defined by an estimated creatinine clearance >30 mL/min
according to the Cockcroft-Gault formula or be measure for creatinine clearance from
24 hour urine collection.

12. Has not had major surgery within 28 days prior to starting study treatment. Central
venous access surgeries and/or placements would not be considered as major surgery.

13. Is eligible for palliative radiotherapy as determined by the treating radiation
oncologist.

Exclusion Criteria:

1. Anticancer treatment within 14 days before the start of trial treatment [e.g.,
cytoreductive therapy, radiotherapy (with the exception of palliative radiotherapy
delivered in a normal organ-sparing technique), immune therapy, or cytokine therapy].

2. Major surgery as determined by the investigator within 28 days before the start of
trial treatment (prior diagnostic biopsy is permitted).

3. Systemic therapy with immunosuppressive agents within 7 days before the start of
treatment; or use of any investigational drug within 28 days before the start of trial
treatment.

4. Subjects with active central nervous system (CNS) metastases with significant
neurological compromise or symptoms are excluded. Subjects with a history of treated
CNS metastases (by surgery or radiation therapy), who show no evolving new
neurological symptoms are eligible for the study.

5. Receipt of any organ transplantation, including allogeneic stem-cell transplantation,
but with the exception of transplants that do not require immunosuppression (e.g.,
corneal transplant, hair transplant).

6. Significant acute or chronic infections including, among others: a. Known history of
testing positive test for human immunodeficiency virus (HIV) or known acquired
immunodeficiency syndrome. b. Active HBV (HBV surface antigen positive) or HCV (HCV
RNA positive). c. Subjects with known active tuberculosis (history of exposure or
history of positive tuberculosis test plus presence of clinical symptoms, physical or
radiographic findings).

7. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent: a. Subjects with type I diabetes, vitiligo, alopecia, psoriasis, hypo- or
hyperthyroid disease not requiring immunosuppressive treatment are eligible b.
Subjects requiring hormone replacement with corticosteroids are eligible if the
steroids are administered only for the purpose of hormonal replacement and at doses ≤
10 mg of prednisone or equivalent per day.

8. Clinically significant cardiovascular/ cerebrovascular disease as follows: cerebral
vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6
months prior to enrollment), unstable angina, congestive heart failure (New York Heart
Association Classification Class > II), or serious cardiac arrhythmia.

9. Clinically relevant diseases (for example, inflammatory bowel disease) and / or
uncontrolled medical conditions, which, in the opinion of the Investigator, might
impair the subject's tolerance or ability to participate in the trial.

10. Vaccine administration within 4 weeks of M7824 administration. Vaccination with live
vaccines while on trial is prohibited. Administration of inactivated vaccines is
allowed (for example, inactivated influenza vaccines).

11. Pregnancy and breast feeding