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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
85
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.
Percentage of Participants by Best Overall Response According to International Myeloma Working Group (IMWG) Criteria
Time frame: 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
Time frame: From start of treatment until 30 days after last dose (up to approximately 36 months)
RP2D of Pomalidomide in the Combinations Tested
Time frame: 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)
Time frame: From start of treatment until 30 days after last dose (up to approximately 36 months)
Duration of Response (DOR) According to IMWG Criteria
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From start of treatment until death from any cause (up to 36 months overall)
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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.
University of Alabama at Birmingham
Birmingham, Alabama, United States
University Of Arkansas
Little Rock, Arkansas, United States
Scripps Clinic Torrey Pines
La Jolla, California, United States
UC Davis; Comprehensive Cancer Center
Sacramento, California, United States
University of California, San Francisco
San Francisco, California, United States
Yale University
New Haven, Connecticut, United States
Mayo Clinic Hospital - Florida
Jacksonville, Florida, United States
Emory Univ Winship Cancer Inst
Atlanta, Georgia, United States
Loyola University Med Center
Maywood, Illinois, United States
Indiana University Health; Goshen Center for Cancer Care
Goshen, Indiana, United States
...and 21 more locations
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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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)