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)
1 other identifier
interventional
85
1 country
31
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 multiple-myeloma
Started Jul 2015
Typical duration for phase_1 multiple-myeloma
31 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 27, 2015
CompletedFirst Posted
Study publicly available on registry
April 30, 2015
CompletedStudy Start
First participant enrolled
July 22, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 19, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
March 19, 2021
CompletedApril 2, 2021
March 1, 2021
5.7 years
April 27, 2015
March 31, 2021
Conditions
Outcome Measures
Primary Outcomes (4)
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 Outcomes (14)
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
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
- +9 more secondary outcomes
Study Arms (11)
Cohort A: ATZ (Run-In)
EXPERIMENTALCohort 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.
Cohort B1: ATZ + LEN (Dose Escalation)
EXPERIMENTALCohort 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.
Cohort C: ATZ + LEN (Post-ASCT):
EXPERIMENTALCohort 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.
Cohort D1: ATZ + DAR (Run-in)
EXPERIMENTALCohort 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.
Cohort D2: ATZ + DAR (Expansion)
EXPERIMENTALCohort 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.
Cohort D3: ATZ + DAR (Progressed)
EXPERIMENTALCohort 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).
Cohort E1: ATZ + DAR + LEN (Dose Escalation)
EXPERIMENTALCohort 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.
Cohort E2: ATZ + DAR + LEN (Expansion)
EXPERIMENTALCohort 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.
Cohort F1: ATZ + DAR + POM (Dose Escalation)
EXPERIMENTALCohort 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.
Cohort F2: ATZ + DAR + POM (Expansion)
ACTIVE COMPARATORCohort 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.
Cohort F3: DAR + POM + Dexamethasone
ACTIVE COMPARATORCohort 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.
Interventions
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.
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.
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.
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.
Participants will receive either 20mg or 40mg of dexamethasone PO every 7 days from Day 1 of each cycle.
Eligibility Criteria
You may qualify if:
- 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)
- +6 more criteria
You may not qualify if:
- 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
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (31)
University of Alabama at Birmingham
Birmingham, Alabama, 35249, United States
University Of Arkansas
Little Rock, Arkansas, 72205, United States
Scripps Clinic Torrey Pines
La Jolla, California, 92037, United States
UC Davis; Comprehensive Cancer Center
Sacramento, California, 95817, United States
University of California, San Francisco
San Francisco, California, 94116, United States
Yale University
New Haven, Connecticut, 06511, United States
Mayo Clinic Hospital - Florida
Jacksonville, Florida, 32224, United States
Emory Univ Winship Cancer Inst
Atlanta, Georgia, 30322, United States
Loyola University Med Center
Maywood, Illinois, 60153, United States
Indiana University Health; Goshen Center for Cancer Care
Goshen, Indiana, 46526, United States
Indiana University Department of Medicine; IU Simon Cancer Center
Indianapolis, Indiana, 46202, United States
University of Louisville
Louisville, Kentucky, 40202-1798, United States
University of Maryland School of Medicine
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Med Ctr; Hem/Onc
Boston, Massachusetts, 02215, United States
Univ of Michigan Medical Ctr
Ann Arbor, Michigan, 48109-0718, United States
Karmanos Cancer Institute.
Detroit, Michigan, 48201, United States
Henry Ford Hospital; Hematology Oncology
Detroit, Michigan, 48202, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Comprehensive Cancer Centers of Nevada
Henderson, Nevada, 89014, United States
Mount SInai Medical Center
New York, New York, 10029, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
UNC Chapel Hill
Chapel Hill, North Carolina, 27514, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44915, United States
University of Oklahoma Health Sciences Center; Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104, United States
Lifespan Cancer Institute
Providence, Rhode Island, 02905, United States
Medical University of South Carolina; Hollings Cancer Center
Charleston, South Carolina, 29425, United States
Texas Oncology-Baylor Sammons Cancer Center
Dallas, Texas, 75246, United States
UT Southwestern MC at Dallas
Dallas, Texas, 75390, United States
Houston Methodist Cancer Center
Houston, Texas, 77030, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
Related Publications (1)
Wong S, Hamidi H, Costa LJ, Bekri S, Neparidze N, Vij R, Nielsen TG, Raval A, Sareen R, Wassner-Fritsch E, Cho HJ. Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM. Front Immunol. 2023 Jul 25;14:1085893. doi: 10.3389/fimmu.2023.1085893. eCollection 2023.
PMID: 37559718DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 27, 2015
First Posted
April 30, 2015
Study Start
July 22, 2015
Primary Completion
March 19, 2021
Study Completion
March 19, 2021
Last Updated
April 2, 2021
Record last verified: 2021-03