A Study of Atezolizumab (Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) Alone or in Combination With an Immunomodulatory Drug and/or Daratumumab in Participants With Multiple Myeloma (MM)

A Phase Ib Study of the Safety and Pharmacokinetics of Atezolizumab (Anti-PD-L1 Antibody) Alone or in Combination With an Immunomodulatory Drug and/or Daratumumab in Patients With Multiple Myeloma (Relapsed/Refractory and Post-Autologous Stem Cell Transplantation)

This multicenter, open-label, Phase I study will evaluate the safety, efficacy, and pharmacokinetics of atezolizumab alone or in combination with daratumumab and/or various immunomodulatory agents in participants with MM who have relapsed or who have undergone autologous stem cell transplantation (ASCT). Cycle length will be 21 days in Cohorts A to C and 28 days in Cohorts D to F.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Lenalidomide; Drug: Daratumumab; Drug: Pomalidomide; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic Torrey Pines
    • Sacramento, California, United States, 95817
      • UC Davis; Comprehensive Cancer Center
    • San Francisco, California, United States, 94116
      • University of California, San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Hospital - Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Univ Winship Cancer Inst
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Med Center
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Indiana University Health; Goshen Center for Cancer Care
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Department of Medicine; IU Simon Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202-1798
      • University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Med Ctr; Hem/Onc
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0718
      • Univ of Michigan Medical Ctr
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital; Hematology Oncology
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute.
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Comprehensive Cancer Centers of Nevada
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44915
      • Cleveland Clinic Foundation
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center; Stephenson Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Lifespan Cancer Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina; Hollings Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern MC at Dallas
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor Sammons Cancer Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Previous diagnosis of MM with objective evidence of measurable disease
• Willing and able to undergo bone marrow aspiration and biopsy tissue sample collection during screening and on study
• Eastern Cooperative Oncology Group (ECOG) performance status score less than or equal to (</=) 2
• Left ventricular ejection fraction (LVEF) greater than or equal to (>/=) 40 percent (%)
• Total bilirubin </=2 times the ULN
• Creatinine </=2.0 milligrams per deciliter (mg/dL), with creatinine clearance (CrCl) using the Cockcroft-Gault formula >/=40 milliliters per minute (mL/min) or 60 mL/min for those who receive lenalidomide
• Corrected calcium at or below ULN
• Transaminase levels </=2.5 times the upper limit of normal (ULN)
• Receipt of >/=1 but not more than 3 prior lines of therapy (Cohorts A, B, C, D1, E)
• Receipt of 2, but not more that 3 prior lines of therapy that must have included a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) (alone or in combination, and are refractory to the last line of treatment(Cohort D2)
• Receipt of >/=2 prior lines of therapy and progressed on treatment with an anti-CD38 monoclonal antibody and are refractory to both a PI and IMiD (Cohort D3)
• Receipt of >/=4 lines of prior therapy and are refractory to the last line of treatment (Cohort F)
• Absolute neutrophil count (ANC) >/=1000 cells per microliter (cells/mcL) (Cohorts A, B, D, E, F)
• Platelet count >/=50,000 cells/mcL, or >/=30,000 cells/mcL if more than 50% bone marrow involvement (Cohorts A, B, D, E, F)
• All participants who are prescribed lenalidomide or pomalidomide must be counseled at a minimum of every 21-28 days about pregnancy precautions and risks of fetal exposure (Cohorts B, C, E, F)
• Agree to be registered in and comply with all requirements of the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program (Cohorts B, C, E)
• Agree to be registered in and comply with all requirements of the Pomalyst REMS program (Cohort F)
• Sufficient recovery from first or second ASCT within 60-120 days of transplant (Cohort C)
• Off antibiotic/antifungal therapy for >/=14 days (Cohort C)
• Completion of any prior radiotherapy (Cohort C)
• ANC >/=1500 cells/mcL (Cohort C)

Exclusion Criteria:

• Other malignancy within 2 years prior to screening, with some exceptions
• Prior therapy with atezolizumab or other immunotherapies including CD137 agonists, anti-programmed death (PD)-1, anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and anti-PD-L1 therapeutic antibodies
• Uncontrolled cancer pain
• Treatment with any investigational drug within 30 days or 5 half-lives of the investigational drug, whichever is longer
• Known hypersensitivity to study drug and/or drug class
• History of autoimmune disease except for controlled, treated thyroidism or Type 1 diabetes
• Prior systemic anti-myeloma therapy within 14 days of Cycle 1 Day 1
• Prior treatment with chimeric antigen receptor (CAR) T cells or other forms of adoptive cellular therapy, with the exception of autologous stem cell transplantation
• Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome
• Plasma cell leukemia (greater than 2,000 cells/mcL of circulating plasma cells by standard differential)
• Immunosuppressive therapy within 6 weeks of Cycle 1 Day 1
• Daily corticosteroid requirement within 2 weeks of Cycle 1 Day 1
• Prior allogeneic stem cell transplant or solid organ transplant
• Active hepatitis B, active hepatitis C, or positive for human immunodeficiency virus (HIV)
• Uncontrolled, clinically significant pulmonary disease (for example, chronic obstructive pulmonary disease, pulmonary hypertension, idiopathic pulmonary fibrosis) that in the opinion of the investigator would put the participant at significant risk for pulmonary complications during the study
• History of pneumonitis
• Uncontrolled intercurrent illness including but not limited to uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breastfeeding females
• Inability to tolerate thromboprophylaxis (Cohorts B, C, E, F)
• Evidence of progressive MM compared to pretransplant evaluation (Cohort C)
• Prior treatment with anti-CD38 therapy including daratumumab (Cohorts D1, D2, E, F)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: ATZ (Run-In); Cohort A will involve a safety run-in to evaluate atezolizumab administered as a single agent in participants with relapsed or refractory MM who have received up to 3 lines of prior treatment. NOTE: This cohort has been completed.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Participants will receive intravenous (IV) atezolizumab until loss of clinical benefit, withdrawal, or study end. Cohorts A to C will receive 1200 milligrams (mg) on Day 1 of each 21-day cycle. Cohorts D to F (combination with daratumumab) will receive 840 mg on Days 2 and 16 of Cycle 1 and on Days 1 and 15 of each 28-day cycle thereafter.; Other Names: Tecentriq, MPDL3280A, "ATZ"
Experimental: Cohort B1: ATZ + LEN (Dose Escalation); Cohort B1 will involve a dose escalation to evaluate atezolizumab administered in combination with ascending-dose lenalidomide in participants with relapsed or refractory MM who have received up to 3 lines of prior treatment. NOTE: This cohort has been completed.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Participants will receive intravenous (IV) atezolizumab until loss of clinical benefit, withdrawal, or study end. Cohorts A to C will receive 1200 milligrams (mg) on Day 1 of each 21-day cycle. Cohorts D to F (combination with daratumumab) will receive 840 mg on Days 2 and 16 of Cycle 1 and on Days 1 and 15 of each 28-day cycle thereafter.; Other Names: Tecentriq, MPDL3280A, "ATZ"; Drug: Lenalidomide; Lenalidomide will be administered orally (PO) until loss of clinical benefit, withdrawal, or study end. Cohort B1 will receive 10, 15, or 25 mg, ascending-dose lenalidomide, on Days 1-14 of each 21-day cycle. Cohort C will receive 10 mg on Days 1-14 of each 21-day cycle, beginning in Cycle 4. Cohort E (combination with daratumumab) will receive 10, 15, or 25 mg on Days 1-21 of each 28-day cycle. Participants in Cohort E1 will receive ascending-dose lenalidomide, and those in Cohort E2 will receive lenalidomide at the MTD as determined in Cohort E1.; Other Names: Revlimid, "LEN"
Experimental: Cohort C: ATZ + LEN (Post-ASCT): Cohort C will evaluate atezolizumab administered in combination with lenalidomide in participants with MM who have measureable disease after ASCT. NOTE: This cohort is closed to enrollment.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Participants will receive intravenous (IV) atezolizumab until loss of clinical benefit, withdrawal, or study end. Cohorts A to C will receive 1200 milligrams (mg) on Day 1 of each 21-day cycle. Cohorts D to F (combination with daratumumab) will receive 840 mg on Days 2 and 16 of Cycle 1 and on Days 1 and 15 of each 28-day cycle thereafter.; Other Names: Tecentriq, MPDL3280A, "ATZ"; Drug: Lenalidomide; Lenalidomide will be administered orally (PO) until loss of clinical benefit, withdrawal, or study end. Cohort B1 will receive 10, 15, or 25 mg, ascending-dose lenalidomide, on Days 1-14 of each 21-day cycle. Cohort C will receive 10 mg on Days 1-14 of each 21-day cycle, beginning in Cycle 4. Cohort E (combination with daratumumab) will receive 10, 15, or 25 mg on Days 1-21 of each 28-day cycle. Participants in Cohort E1 will receive ascending-dose lenalidomide, and those in Cohort E2 will receive lenalidomide at the MTD as determined in Cohort E1.; Other Names: Revlimid, "LEN"
Experimental: Cohort D1: ATZ + DAR (Run-in); Cohort D1 will involve a safety run-in to evaluate atezolizumab administered in combination with daratumumab in participants with relapsed or refractory MM who have received up to 3 lines of prior treatment.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Participants will receive intravenous (IV) atezolizumab until loss of clinical benefit, withdrawal, or study end. Cohorts A to C will receive 1200 milligrams (mg) on Day 1 of each 21-day cycle. Cohorts D to F (combination with daratumumab) will receive 840 mg on Days 2 and 16 of Cycle 1 and on Days 1 and 15 of each 28-day cycle thereafter.; Other Names: Tecentriq, MPDL3280A, "ATZ"; Drug: Daratumumab; Participants will receive 16 milligrams per kilogram (mg/kg) IV daratumumab until loss of clinical benefit, withdrawal, or study end. Treatment will be per the U.S. Package Insert and given on Days 1, 8, 15, 22 of Cycles 1 and 2; on Days 1 and 15 of Cycles 3 to 6; and on Day 1 of each 28-day cycle thereafter.; Other Names: Darzalex, "DAR"
Experimental: Cohort D2: ATZ + DAR (Expansion); Cohort D2 will involve an expansion to evaluate atezolizumab administered in combination with daratumumab in participants with relapsed or refractory MM who have received 2 but no more than 3 lines of prior treatment that must have included a PI and IMiD and are refractory to the last line of treatment.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Participants will receive intravenous (IV) atezolizumab until loss of clinical benefit, withdrawal, or study end. Cohorts A to C will receive 1200 milligrams (mg) on Day 1 of each 21-day cycle. Cohorts D to F (combination with daratumumab) will receive 840 mg on Days 2 and 16 of Cycle 1 and on Days 1 and 15 of each 28-day cycle thereafter.; Other Names: Tecentriq, MPDL3280A, "ATZ"; Drug: Daratumumab; Participants will receive 16 milligrams per kilogram (mg/kg) IV daratumumab until loss of clinical benefit, withdrawal, or study end. Treatment will be per the U.S. Package Insert and given on Days 1, 8, 15, 22 of Cycles 1 and 2; on Days 1 and 15 of Cycles 3 to 6; and on Day 1 of each 28-day cycle thereafter.; Other Names: Darzalex, "DAR"
Experimental: Cohort D3: ATZ + DAR (Progressed); Cohort D3 will involve an expansion to evaluate atezolizumab in combination with daratumumab in participants with relapsed or refractory MM who have received 2 or more lines of prior treatment and have progressed with an anti-cluster of differentiation (CD) 38 monoclonal antibody, either alone or in combination, and are refractory to both a proteasome inhibitor (PI) and immunomodulatory drug (IMiD).	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Participants will receive intravenous (IV) atezolizumab until loss of clinical benefit, withdrawal, or study end. Cohorts A to C will receive 1200 milligrams (mg) on Day 1 of each 21-day cycle. Cohorts D to F (combination with daratumumab) will receive 840 mg on Days 2 and 16 of Cycle 1 and on Days 1 and 15 of each 28-day cycle thereafter.; Other Names: Tecentriq, MPDL3280A, "ATZ"; Drug: Daratumumab; Participants will receive 16 milligrams per kilogram (mg/kg) IV daratumumab until loss of clinical benefit, withdrawal, or study end. Treatment will be per the U.S. Package Insert and given on Days 1, 8, 15, 22 of Cycles 1 and 2; on Days 1 and 15 of Cycles 3 to 6; and on Day 1 of each 28-day cycle thereafter.; Other Names: Darzalex, "DAR"
Experimental: Cohort E1: ATZ + DAR + LEN (Dose Escalation); Cohort E1 will involve a dose escalation to evaluate atezolizumab administered in combination with daratumumab and ascending-dose lenalidomide in participants with relapsed or refractory MM who have received up to 3 lines of prior treatment. NOTE: This cohort is closed to enrollment.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Participants will receive intravenous (IV) atezolizumab until loss of clinical benefit, withdrawal, or study end. Cohorts A to C will receive 1200 milligrams (mg) on Day 1 of each 21-day cycle. Cohorts D to F (combination with daratumumab) will receive 840 mg on Days 2 and 16 of Cycle 1 and on Days 1 and 15 of each 28-day cycle thereafter.; Other Names: Tecentriq, MPDL3280A, "ATZ"; Drug: Lenalidomide; Lenalidomide will be administered orally (PO) until loss of clinical benefit, withdrawal, or study end. Cohort B1 will receive 10, 15, or 25 mg, ascending-dose lenalidomide, on Days 1-14 of each 21-day cycle. Cohort C will receive 10 mg on Days 1-14 of each 21-day cycle, beginning in Cycle 4. Cohort E (combination with daratumumab) will receive 10, 15, or 25 mg on Days 1-21 of each 28-day cycle. Participants in Cohort E1 will receive ascending-dose lenalidomide, and those in Cohort E2 will receive lenalidomide at the MTD as determined in Cohort E1.; Other Names: Revlimid, "LEN"; Drug: Daratumumab; Participants will receive 16 milligrams per kilogram (mg/kg) IV daratumumab until loss of clinical benefit, withdrawal, or study end. Treatment will be per the U.S. Package Insert and given on Days 1, 8, 15, 22 of Cycles 1 and 2; on Days 1 and 15 of Cycles 3 to 6; and on Day 1 of each 28-day cycle thereafter.; Other Names: Darzalex, "DAR"
Experimental: Cohort E2: ATZ + DAR + LEN (Expansion); Cohort E2 will involve an expansion to evaluate atezolizumab administered in combination with daratumumab and the maximum tolerated dose (MTD) of lenalidomide determined in Cohort E1 in participants with relapsed or refractory MM who have received up to 3 lines of prior treatment. NOTE: This cohort is closed to enrollment.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Participants will receive intravenous (IV) atezolizumab until loss of clinical benefit, withdrawal, or study end. Cohorts A to C will receive 1200 milligrams (mg) on Day 1 of each 21-day cycle. Cohorts D to F (combination with daratumumab) will receive 840 mg on Days 2 and 16 of Cycle 1 and on Days 1 and 15 of each 28-day cycle thereafter.; Other Names: Tecentriq, MPDL3280A, "ATZ"; Drug: Lenalidomide; Lenalidomide will be administered orally (PO) until loss of clinical benefit, withdrawal, or study end. Cohort B1 will receive 10, 15, or 25 mg, ascending-dose lenalidomide, on Days 1-14 of each 21-day cycle. Cohort C will receive 10 mg on Days 1-14 of each 21-day cycle, beginning in Cycle 4. Cohort E (combination with daratumumab) will receive 10, 15, or 25 mg on Days 1-21 of each 28-day cycle. Participants in Cohort E1 will receive ascending-dose lenalidomide, and those in Cohort E2 will receive lenalidomide at the MTD as determined in Cohort E1.; Other Names: Revlimid, "LEN"; Drug: Daratumumab; Participants will receive 16 milligrams per kilogram (mg/kg) IV daratumumab until loss of clinical benefit, withdrawal, or study end. Treatment will be per the U.S. Package Insert and given on Days 1, 8, 15, 22 of Cycles 1 and 2; on Days 1 and 15 of Cycles 3 to 6; and on Day 1 of each 28-day cycle thereafter.; Other Names: Darzalex, "DAR"
Experimental: Cohort F1: ATZ + DAR + POM (Dose Escalation); Cohort F1 will involve a dose escalation to evaluate atezolizumab administered in combination with daratumumab and ascending-dose pomalidomide in participants with relapsed or refractory MM who have received 4 or more lines of prior treatment and are refractory to the last line of treatment. NOTE: This cohort has been completed.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Participants will receive intravenous (IV) atezolizumab until loss of clinical benefit, withdrawal, or study end. Cohorts A to C will receive 1200 milligrams (mg) on Day 1 of each 21-day cycle. Cohorts D to F (combination with daratumumab) will receive 840 mg on Days 2 and 16 of Cycle 1 and on Days 1 and 15 of each 28-day cycle thereafter.; Other Names: Tecentriq, MPDL3280A, "ATZ"; Drug: Daratumumab; Participants will receive 16 milligrams per kilogram (mg/kg) IV daratumumab until loss of clinical benefit, withdrawal, or study end. Treatment will be per the U.S. Package Insert and given on Days 1, 8, 15, 22 of Cycles 1 and 2; on Days 1 and 15 of Cycles 3 to 6; and on Day 1 of each 28-day cycle thereafter.; Other Names: Darzalex, "DAR"; Drug: Pomalidomide; Pomalidomide will be administered PO until loss of clinical benefit, withdrawal, or study end. Cohort F (combination with daratumumab) will receive 2 or 4 mg on Days 1-21 of each 28-day cycle. Participants in Cohort F1 will receive ascending-dose pomalidomide, and those in Cohort F2 will receive pomalidomide at the MTD as determined in Cohort F1.; Other Names: Pomalyst, "POM"
Active Comparator: Cohort F2: ATZ + DAR + POM (Expansion); Cohort F2 will involve an expansion to evaluate atezolizumab administered in combination with daratumumab and the MTD of pomalidomide determined in Cohort F1 in participants with relapsed or refractory MM who have received 4 or more lines of prior treatment and are refractory to the last line of treatment. NOTE: This cohort is randomized.	Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Participants will receive intravenous (IV) atezolizumab until loss of clinical benefit, withdrawal, or study end. Cohorts A to C will receive 1200 milligrams (mg) on Day 1 of each 21-day cycle. Cohorts D to F (combination with daratumumab) will receive 840 mg on Days 2 and 16 of Cycle 1 and on Days 1 and 15 of each 28-day cycle thereafter.; Other Names: Tecentriq, MPDL3280A, "ATZ"; Drug: Daratumumab; Participants will receive 16 milligrams per kilogram (mg/kg) IV daratumumab until loss of clinical benefit, withdrawal, or study end. Treatment will be per the U.S. Package Insert and given on Days 1, 8, 15, 22 of Cycles 1 and 2; on Days 1 and 15 of Cycles 3 to 6; and on Day 1 of each 28-day cycle thereafter.; Other Names: Darzalex, "DAR"; Drug: Pomalidomide; Pomalidomide will be administered PO until loss of clinical benefit, withdrawal, or study end. Cohort F (combination with daratumumab) will receive 2 or 4 mg on Days 1-21 of each 28-day cycle. Participants in Cohort F1 will receive ascending-dose pomalidomide, and those in Cohort F2 will receive pomalidomide at the MTD as determined in Cohort F1.; Other Names: Pomalyst, "POM"
Active Comparator: Cohort F3: DAR + POM + Dexamethasone; Cohort F3 is an expansion control arm for cohort F2. Participants will receive daratumumab in combination with pomalidomide at the MTD and dexamethasone. NOTE: This cohort is randomized.	Drug: Daratumumab; Participants will receive 16 milligrams per kilogram (mg/kg) IV daratumumab until loss of clinical benefit, withdrawal, or study end. Treatment will be per the U.S. Package Insert and given on Days 1, 8, 15, 22 of Cycles 1 and 2; on Days 1 and 15 of Cycles 3 to 6; and on Day 1 of each 28-day cycle thereafter.; Other Names: Darzalex, "DAR"; Drug: Pomalidomide; Pomalidomide will be administered PO until loss of clinical benefit, withdrawal, or study end. Cohort F (combination with daratumumab) will receive 2 or 4 mg on Days 1-21 of each 28-day cycle. Participants in Cohort F1 will receive ascending-dose pomalidomide, and those in Cohort F2 will receive pomalidomide at the MTD as determined in Cohort F1.; Other Names: Pomalyst, "POM"; Drug: Dexamethasone; Participants will receive either 20mg or 40mg of dexamethasone PO every 7 days from Day 1 of each cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants by Best Overall Response According to International Myeloma Working Group (IMWG) Criteria	From Day 1 of Cycle 2 (cycle = 21 or 28 days) until progression, withdrawal, or study end (up to 36 months overall)
Recommended Phase II Dose (RP2D) of Lenalidomide in the Combinations Tested	From start of treatment until 30 days after last dose (up to approximately 36 months)
RP2D of Pomalidomide in the Combinations Tested	From start of treatment until 30 days after last dose (up to approximately 36 months)
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)	From start of treatment until 30 days after last dose (up to approximately 36 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) According to IMWG Criteria		From first observed response until the date of first recorded progression or death from any cause (up to 36 months overall)
Progression-Free Survival (PFS) According to IMWG Criteria		From start of treatment until the date of first recorded progression or death from any cause (up to 36 months overall)
Percentage of Participants with Objective Response According to IMWG Criteria		From Day 1 of Cycle 2 until progression, withdrawal, or study end (up to 36 months overall). For Cohort D3 Only: 6, 9, and 12 months.
Overall Survival		From start of treatment until death from any cause (up to 36 months overall)
Maximum Observed Serum Concentration (Cmax) of Atezolizumab	Predose (0 h) and postdose (0.5 h) (infusion = 0.5-1 h) on Day 1 of Cycles 1, 3 (cycle = 21 or 28 days) and Day 2 of Cycle 1; predose (0 h) on Day 1 of Cycles 2, 4, 8; then every 8 cycles until/at treatment discontinuation (up to 36 months); and 90 days after last dose (up to 36 months overall)	From predose (0 hours [h]) on Day 1 of Cycle 1 until treatment discontinuation (up to 36 months overall); see Outcome Measure Description for details
Minimum Observed Serum Concentration (Cmin) of Atezolizumab		Predose (0 h) on Day 1 of Cycles 1, 2, 3, 4, 8 (cycle = 21 or 28 days) and Day 2 of Cycle 1; then every 8 cycles until/at treatment discontinuation (up to 36 months); and 90 days after last dose (up to 36 months overall)
Cmax of Lenalidomide		Predose (0 h) and postdose (1 h) on Day 1 of Cycles 1, 4 (cycle = 21 days); predose (0 h) and postdose (0.5, 1, 2, 4, 8 h) on Day 15 of Cycles 1, 3; predose (0 h) and postdose (2 h) on Day 15 of Cycles 2, 4, 8
Cmin of Lenalidomide		Predose (0 h) on Day 1 of Cycles 1, 4 (cycle = 21 days) and Day 15 of Cycles 1, 2, 3, 4, 8
Cmax of Pomalidomide		Predose (0 h) and postdose (1, 2, 4, 6, 8 h) on Day 15 of Cycles 1, 3 (cycle = 28 days); predose (0 h) and postdose (4 h) on Day 15 of Cycles 2, 4, 8
Cmin of Pomalidomide		Predose (0 h) on Day 15 of Cycles 1, 2, 3, 4, 8 (cycle = 28 days)
Cmax of Daratumumab	Predose (0 h) and postdose (0.5 h) (infusion ~3-6 h) on Day 1 of Cycles 1, 3 (cycle = 28 days); predose (0 h) on Day 1 of Cycles 2, 4, 8; then every 8 cycles until/at treatment discontinuation (up to 36 months); and 90 days after last dose (up to 36 months overall)	From predose (0 h) on Day 1 of Cycle 1 until treatment discontinuation (up to 36 months overall); see Outcome Measure Description for details
Cmin of Daratumumab		Predose (0 h) on Day 1 of Cycles 1, 2, 3, 4, 8 (cycle = 28 days); then every 8 cycles until/at treatment discontinuation (up to 36 months); and 90 days after last dose (up to 36 months overall)
Change in Number of Participants With Anti-Drug Antibody (ADA) Response to Atezolizumab from Baseline to End of Study	From treatment start until study end; assessed predose (0 h) on Day 1 of Cycles 1, 2, 3, 4, 8 (cycle = 21 or 28 days) and Day 2 of Cycle 1; then every 8 cycles until/at treatment discontinuation (up to 36 months); and 90 days after last dose (up to 36 months overall)	From treatment start until study end (up to 36 months overall); see Outcome Measure Description for details
Change in Number of Participants With ADA Response to Daratumumab from Baseline to End of Study		From treatment start until study end; assessed predose (0 h) on Day 1 of Cycles 1, 3, 8 (cycle = 28 days); at treatment discontinuation (up to 36 months); and 90 days after last dose (up to 36 months overall)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2015
• Primary Completion (Actual): March 19, 2021
• Study Completion (Actual): March 19, 2021

Study Registration Dates

• First Submitted: April 27, 2015
• First Submitted That Met QC Criteria: April 29, 2015
• First Posted (Estimate): April 30, 2015

Study Record Updates

• Last Update Posted (Actual): April 2, 2021
• Last Update Submitted That Met QC Criteria: March 31, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Antibodies; Pomalidomide; Lenalidomide; Daratumumab; Antibodies, Monoclonal; Atezolizumab
• Other Study ID Numbers: GO29695