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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A: ATZ (Run-In) | Experimental | 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. |
|
| Cohort B1: ATZ + LEN (Dose Escalation) | Experimental | 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. |
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| Cohort C: ATZ + LEN (Post-ASCT): | Experimental | 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. |
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| Cohort D1: ATZ + DAR (Run-in) | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody | Drug | 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. |
| Measure | Description | 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) |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35249 | United States | ||
| University Of Arkansas |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37559718 | Derived | 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. |
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| Cohort D2: ATZ + DAR (Expansion) | Experimental | 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. |
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| Cohort D3: ATZ + DAR (Progressed) | Experimental | 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). |
|
| Cohort E1: ATZ + DAR + LEN (Dose Escalation) | Experimental | 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. |
|
| Cohort E2: ATZ + DAR + LEN (Expansion) | Experimental | 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. |
|
| Cohort F1: ATZ + DAR + POM (Dose Escalation) | Experimental | 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. |
|
| Cohort F2: ATZ + DAR + POM (Expansion) | Active Comparator | 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. |
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| Cohort F3: DAR + POM + Dexamethasone | Active Comparator | 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. |
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| Daratumumab | Drug | 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. |
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| Lenalidomide | Drug | 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. |
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| Pomalidomide | Drug | 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. |
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| Dexamethasone | Drug | Participants will receive either 20mg or 40mg of dexamethasone PO every 7 days from Day 1 of each cycle. |
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| 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) |
| 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 |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| D000069446 | Atazanavir Sulfate |
| C556306 | daratumumab |
| D000077269 | Lenalidomide |
| C467566 | pomalidomide |
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D054833 | Isoindoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
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