Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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: 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: 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 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: 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: 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 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.

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35249

University Of Arkansas
Little Rock, Arkansas 72205

Scripps Clinic Torrey Pines
La Jolla, California 92037

University of California, San Francisco
San Francisco, California 94116

Yale University
New Haven, Connecticut 06511

Mayo Clinic Hospital - Florida
Jacksonville, Florida 32224

Emory Univ Winship Cancer Inst
Atlanta, Georgia 30322

Indiana University Health; Goshen Center for Cancer Care
Goshen, Indiana 46526

University of Maryland School of Medicine
Baltimore, Maryland 21201

Massachusetts General Hospital
Boston, Massachusetts 02114

Beth Israel Deaconess Med Ctr; Hem/Onc
Boston, Massachusetts 02215

Univ of Michigan Medical Ctr
Ann Arbor, Michigan 48109-0718

Karmanos Cancer Institute.
Detroit, Michigan 48201

Washington University School of Medicine
Saint Louis, Missouri 63110

Comprehensive Cancer Centers of Nevada
Henderson, Nevada 89014

Mount SInai Medical Center
New York, New York 10029

Memorial Sloan-Kettering Cancer Center
New York, New York 10065

University of Oklahoma Health Sciences Center; Stephenson Cancer Center
Oklahoma City, Oklahoma 73104

Lifespan Cancer Institute
Providence, Rhode Island 02905

Medical University of South Carolina; Hollings Cancer Center
Charleston, South Carolina 29425

Texas Oncology-Baylor Sammons Cancer Center
Dallas, Texas 75246

Huntsman Cancer Institute
Salt Lake City, Utah 84112

Seattle Cancer Care Alliance
Seattle, Washington 98109

More Details

NCT ID
NCT02431208
Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: GO29695 www.roche.com/about_roche/roche_worldwide.htm
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.