This multicenter, open-label, Phase I study will evaluate the safety and pharmacokinetics of MPDL3280A alone or in combination with lenalidomide in patients with multiple myeloma who have relapsed or who have undergone autologous stem cell transplantation (ASCT). The planned duration of this study is approximately 36 months. Trial Overview Treatments: Lenalidomide, MPDL3280A Enrollment: Approx. 46 patients will be enrolled in this study. Who Sponsors this trial? Genentech Phase: Phase 1 Trial ID: MM-0728 Inclusion Criteria

• Age greater than or equal to 18 years
• Previous diagnosis of multiple myeloma with objective evidence of measurable disease
• Willing and able to undergo bone marrow aspiration and biopsy tissue sample collection during screening
• Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less, meaning you may be symptomatic, <50% in bed during the day (Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours)
• Receipt of 1 to 3 prior therapies with a proteasome inhibitor and lenalidomide, with disease progression following the most recent therapy (Relapsed Cohorts)

• Active or prior malignancy which may confound the study endpoint assessments
• Prior therapy with MPDL3280A or other immunotherapies including cluster of differentiation 137 (CD137) agonists or anti-programmed death (PD)-1, anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4), and other anti-PD-L1 antibodies
• Uncontrolled cancer pain
• Treatment with any investigational drug within 30 days
• Known hypersensitivity to study drug and/or drug class
• History of autoimmune disease excepted controlled, treated thyroidism or type 1 diabetes Alkylating agents within 28 days or other anti-cancer therapy within 21 days
• Immunosuppressive therapy within 6 weeks of treatment initiation
• Daily corticosteroid requirement within 2 weeks of treatment initiation
• Prior allogeneic stem cell transplant or solid organ transplant
• Active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV)

After you read the Informed Consent Form, you will have a chance to discuss it with your family and friends. If you decide to participate in the study, you will be asked to sign the Informed Consent Form. No study testing or study evaluations will be done before you sign this consent form. The following tests and assessments will be done at the first visit:

• Your medical history, surgical history, and cancer history will be reviewed, including any previous treatment you have received for your cancer.
• Your demographic information will be recorded, including your date of birth, sex, race, and ethnicity.
• You will be asked about the medications you have taken within 7 days before your screening visit.
• You will have a complete physical examination (including neurological exam to determine if you have peripheral neuropathy [loss of sensation or nerve pain]) performed to identify any conditions that you might have or have had. Your cancer will be assessed by physical examination. Radiologic imaging scans will be done to assess your cancer. This will include scans of your chest, abdomen, pelvis, and brain. These imaging tests may be performed up to 35 days before you receive your first study treatment.
• An X-ray scan of your bones, called a skeletal survey, will be done to look for myeloma in the bones. Your performance status (a measure of how you are able to perform ordinary tasks and able to carry out daily activities) will be evaluated.
• Your height, weight, and vital signs (heart rate, breathing rate, blood pressure, oxygen level, and temperature) will be measured.
• An electrocardiogram (ECG) will be done to record the electrical activity of your heart. An ECG requires temporary placement of electrical sensors on parts of your upper body (torso).
• Evaluation of your heart function by an ultrasound (echocardiogram) or nuclear medicine test (MUGA)
• Blood samples (approximately 2?3 tablespoons) will be taken from a vein in your arm for laboratory blood tests within 14 days before your first study treatment. These tests will evaluate your blood counts, liver and kidney function, blood clotting ability, status of your myeloma, and any other safety evaluations.
• Approximately 1?2 tablespoons of blood will be taken to test for Epstein-Barr, hepatitis B, and hepatitis C viruses.
• Approximately 1 tablespoon of blood will be taken to test for human immunodeficiency virus (HIV).
• A urine sample will be collected for standard laboratory tests and urine will be collected for 24 hours for myeloma-specific tests.
• If you are a woman able to bear children, even if you have had your tubes tied (tubal ligation), you will also have a blood sample (approximately 1 teaspoon) taken for a pregnancy test within 14 days before your first study treatment.
• Approximately 1?2 tablespoons of blood will be taken to measure immune cells.
• A bone marrow biopsy and aspirate will be performed during screening.
• You will undergo computed tomography (CT) or magnetic resonance imaging (MRI) scans to determine if your myeloma has spread outside of the bone marrow and/or bones.
• The initial screening visit may take approximately 3?4 hours, depending on clinic scheduling.

If the examinations, tests, and procedures show that you can be in the study and you choose to take part, you will be enrolled into the study. You will be assigned by a computer program to one of three treatment groups based on your disease status and the cohort (groups) and/or dose level that is available at the time of your enrollment. If you have been assigned to Cohort A or Cohort C, you will receive MPDL3280A alone. If you have been assigned to Cohort B, you will receive MDPL3280A and lenalidomide. All treatment cycles are 21 days long. You and or study doctor will know which treatment you will receive. You will receive study treatment as described below. Cohorts A and C: You will receive MPDL3280A every 3 weeks starting on the first day of the first cycle and then on the first day of every cycle thereafter at a dose of 1200 mg (this dose will remain the same during the study) directly into your bloodstream through a vein in your arm (infusion). If your myeloma has returned, even after a previous ASCT, you may be assigned to Cohort A. If you have recently had an ASCT and have leftover disease, then you will be assigned to Cohort C. Cohort B: You will receive MPDL3280A every 3 weeks starting on the first day of the first cycle and then on the first day of every cycle thereafter at a dose of 1200 mg (this dose will remain the same during the study) directly into your bloodstream through a vein in your arm (infusion). In addition, you will receive lenalidomide capsules (1?3) by mouth for the first 14 days of each cycle. Several different doses of lenalidomide will be tested to find the most effective dose when combined with MPDL3280A. You will be asked to write down when you take lenalidomide on a patient diary. Trial Locations For trial contaction information, please visit Roche.com or call (888) 662-6728 (US only) or email global.rochegenentechtrials@roche.com. Please reference Study ID Number: GO29695 This trial has 8 active trial sites in the US. Find the closest site to your location by clicking at SparkCures here. Spark Cures: To Find Additional Trials for Myeloma Patients To find additional clinical trials for multiple myeloma, click here. You can search by drug, type of disease, location and type of treatment.