A Study of Cobimetinib Administered as Single Agent and in Combination With Venetoclax, With or Without Atezolizumab, in Participants With Relapsed and Refractory Multiple Myeloma

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy of at least 12 weeks
• Documented multiple myeloma
• Received 3 to 5 prior lines of therapy for multiple myeloma, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
• Achieved a response (minimal response [MR] or better) to at least one prior regimen
• Documented evidence of progressive disease (as defined by the IMWG criteria) on or after their last prior therapy, or participants who were intolerant to their last prior therapy
• Toxicities resulting from previous therapy (including peripheral neuropathy) that must be resolved or stabilized to Grade 1

Exclusion criteria

• Anti-myeloma treatment within 14 days or 5 pharmacokinetic (PK) half-lives of the treatment, whichever is longer, before the date of randomization
• Completion of autologous stem cell transplant within 100 days prior to the date of randomization
• Prior allogeneic stem cell transplant as well as prior solid organ transplant
• Spinal cord compression not definitively treated with surgery and/or radiation
• Prior treatment with MEK inhibitors, B-cell lymphoma-2 (Bcl-2) inhibitors, or immune checkpoint inhibitor therapies including anti-cytotoxic T-lymphocyte associated protein-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1) or anti-programmed death-ligand 1 (anti-PD-L1)
• Treatment with systemic immunostimulatory agents within 28 days or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication within 14 days prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
• Prior radiation therapy within 14 days prior to study enrollment and/or persistence of radiation-related adverse effects
• History or evidence of retinal pathology on ophthalmic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration
• Left ventricular ejection fraction (LVEF) below institutional lower limit of normal
• History of clinically significant cardiovascular dysfunction
• Any previous venous thromboembolism greater than (>) Grade 3 within 12 months of study enrollment
• History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins (for participants in Arm C only)
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Active or history of autoimmune disease or immune deficiency
• History of malabsorption or other condition that would interfere with absorption of study drugs
• Active tuberculosis
• Severe infection within 28 days prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 14 days prior to initiation of study treatment
• Positive test results for hepatitis B (hepatitis B surface antigen [HBsAg] and/or total hepatitis B core antibody [HBcAb]) or hepatitis C virus (HCV) antibody
• Known history of human immunodeficiency virus (HIV) seropositivity
• Treatment with a live, attenuated influenza vaccine (e.g., FluMist) within 28 days prior to Cycle 1 Day 1, at any time during the study, and for at least 5 months after the last dose of study drug (for participants in Arm C only)
• Received strong cytochrome P-3A (CYP3A) inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, and moderate CYP3A inducers within 7 days prior to the initiation of study treatment