Elotuzumab Plus Lenalidomide (Elo/Rev) for Serologic Relapse/Progression While on Lenalidomide

This is a randomized parallel 2-cohort phase 2 study of elotuzumab given at 10 mg/kg weekly
during induction in combination with lenalidomide (either 25 mg or 10 mg) in patients with
multiple myeloma who progress or relapse serologically while on single agent lenalidomide
maintenance.

The combination therapy with elotuzumab and lenalidomide will be continued until further
progression of myeloma (based on response criteria) or intolerability.

Inclusion Criteria:

- Patients with multiple myeloma who demonstrate evidence of serologic
relapse/progression while on lenalidomide maintenance given as part of first line
therapy (including upfront high-dose chemotherapy followed by autologous hematopoietic
cell transplantation (HCT)) without symptomatic relapse/progression. Lenalidomide
maintenance is defined as single agent lenalidomide therapy of any doses up to 10 mg
PO daily for up to 28 days (28-day cycle).

- Male or female patients aged ≥ 18 years old

- Ability to provide written informed consent obtained prior to participation in the
study and any related procedures being performed

- Measurable disease as outlined in protocol guidelines

- Participants must meet laboratory criteria as outlined in protocol guidelines

Exclusion Criteria:

- Prior elotuzumab

- Patients with clinical relapse/progression as per the International Myeloma Working
Group (IMWG) Uniform Response Criteria for Multiple Myeloma defined as one or more of
the following criteria:

- Development of new soft tissue plasmacytomas or bone lesions (osteoporotic
fractures do not constitute progression)

- Definite increase in the size of existing plasmacytomas or bone lesions. A
definite increase is defined as a 50% (and ≥1 cm) increase as measured serially
of the measurable lesion

- Hypercalcaemia (>11 mg/dL);

- Decrease in hemoglobin of ≥2 g/dL not related to therapy or other
non-myeloma-related conditions;

- Rise in serum creatinine by 2 mg/dL or more from the start of the therapy and
attributable to myeloma

- Hyperviscosity related to serum paraprotein

- Women who are pregnant or breast feeding or women of childbearing potential (WOCBP)
not using an effective method of birth control. Women of childbearing potential must
have a negative serum pregnancy testing within 7 days prior to the administration of
drug.

- Male patients whose sexual partners are WOCBP not using effective birth control

- Patients with a prior malignancy with in the last 5 years (except for basal or
squamous cell carcinoma, or in situ cancer of the cervix)

- Patients with known positivity for human immunodeficiency virus (HIV)) or hepatitis C;
baseline testing for HIV and hepatitis C is not required

- Patients with a diagnosis of POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein, and skin changes) or plasma cell leukemia (> 2.0 ×
10^9/L circulating plasma cells by standard differential)