An Exploratory Study to Evaluate the Combination of Elotuzumab and Nivolumab With and Without Pomalidomide in Relapsed Refractory Multiple Myeloma

This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational drug combination to learn whether the combination
works in treating a specific disease. "Investigational" means that the drug combination is
being studied.

This study has two parts. Each part tests a different combination of drugs.

- In Part 1 participants will be given elotuzumab and nivolumab.

- In Part 2 participants will be given elotuzumab, nivolumab, pomalidomide, and
dexamethasone.

Each of these drugs works in a different way to help the body fight multiple myeloma. The
drugs are being tested in different combinations to see if they are more effective when taken
together.

Elotuzumab is an antibody, that stimulates the immune system to fight your disease. The FDA
(the U.S. Food and Drug Administration) has approved elotuzumab in combination with
lenalidomide as a treatment option for this disease.

In this research study, the participant will receive pomalidomide which is an
immunomodulatory drug. This means that pomalidomide modulates the immune system to help fight
the disease. The FDA has approved pomalidomide as a treatment option for this disease after
receiving two other therapies.

Dexamethasone, also FDA approved, is a type of steroid and is usually combined with other
chemotherapy for the treatment of blood cancers, such as myeloma and leukemias.

The FDA has not approved nivolumab for this specific disease but it has been approved for
other uses, specifically lung cancer. Nivolumab works by blocking an inhibitory signal within
immune cells, potentially allowing the immune system to fight the cancer.

In this research study the investigators are looking to see if the combination of elotuzumab,
nivolumab, pomalidomide, and dexamethasone is effective in fighting the cancer.

Inclusion Criteria:

- Male or female patient ≥ age 18 years

- Patient is able to understand and has given voluntary written informed consent before
performance of any study-related procedures not part of normal medical care, with the
understanding that consent may be withdrawn by the patient at any time without
prejudice to their future medical care

- Patient has been previously diagnosed with MM based on standard International Myeloma
Working Group (IMWG) criteria and currently requires treatment.

- Patient must have received at least two previous lines of therapy for multiple myeloma
including lenalidomide or thalidomide and a proteasome inhibitor (bortezomib,
carfilzomib or ixazomib).

- Patient must have demonstrated disease progression on or within 60 days of completion
of the last therapy. Patient has measurable disease defined as at least one of the
following:

- Serum M protein ≥ 0.5 g/dL (≥5 g/L)

- Urine M protein ≥200 mg/24 hours

- Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and
an abnormal serum FLC ratio (<0.26 or >1.65)

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Appendix A)

- Negative serum or urine pregnancy test for women of child-bearing potential

- Screening Laboratory parameters:

- Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L). Granulocyte
colony-stimulating factor (GCSF) is not permitted during screening to meet eligibility
criteria and within 14 days of initiation of therapy

- Platelet count ≥ 75,000 cells/dL (75 x 109/L) Platelet transfusion is not
permitted during screening to meet eligibility criteria and within 14 days of
initiation of therapy

- Hemoglobin ≥ 8.0 g/dl ( red blood cell (RBC) transfusions are permitted during
the screening period)

- Total Bilirubin ≤ 1.5 X upper limit of normal (ULN) (Patients with known Gilbert
Syndrome are allowed to have total bilirubin < 3.0 mg/dL)

- Aspartate transaminase (AST, or SGOT) and alanine transaminase (ALT, or SGPT) ≤
3.0x ULN

- Estimated creatinine clearance by Cockcroft-Gault formula ≥ 40 mL/min

- Serum creatinine < 1.5 X ULN. (Appendix C)

Exclusion Criteria:

- Diagnosed or treated for another malignancy within 3 years prior to enrollment, with
the exception of complete resection of basal cell carcinoma or squamous cell carcinoma
of the skin, an in situ malignancy, or low risk prostate cancer after curative
therapy.

- Prior therapy with pomalidomide

- Prior treatment with monoclonal antibodies including elotuzumab

- Prior therapy with anti-programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1)
agents.

- Received any investigational drug within 14 days or 5 half-lives of the
investigational drug, whichever is longer.

- Prior anti-cancer therapy within 14 days.

- Patient has any Grade 3 or > unresolved adverse reaction from previous treatment.
Previous allogeneic stem cell transplantation with active graft-versus-host disease
(GVHD) or being under immunosuppressive therapy in the last 2 months prior to
inclusion in the trial.

- Autologous stem cell transplant if < 12 weeks from enrollment.

- Daily requirement for oral corticosteroids (equivalent to > 10 mg/day prednisone
daily) Inhaled or topical corticosteroids are allowed.

- Patient is human immunodeficiency virus (HIV) positive,.

- Patient is Hepatitis B Surface antigen-positive.

- Patient has active hepatitis C infection.

- Patient has an autoimmune disease. (Subjects are permitted to enroll if they have
vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
condition only requiring hormone replacement, psoriasis not requiring systemic
treatment, or conditions not expected to recur in the absence of an external trigger).

- Any clinically significant, uncontrolled medical conditions that, in the treating
Investigator's opinion, would impose excessive risk to the patient or may interfere
with compliance or interpretation of the study results. Uncontrolled intercurrent
illness may include, but is not limited to, ongoing or active infection, symptomatic
congestive heart failure, unstable angina pectoris, clinically significant cardiac
arrhythmia, or psychiatric illness/social situations as determined by treating
investigator that would limit compliance with study requirements.

- History of erythema multiforme or severe hypersensitivity to prior IMiD's®

- Inability to tolerate thromboprophylaxis

- Known severe intolerance to prior steroid therapy (Grade 3 or above adverse event
which was unresponsive to a dose reduction)