Multiple MyelomaPhase 1NCT02431208
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 1 study testing Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Daratumumab and Lenalidomide in people with Multiple Myeloma, run by Hoffmann-La Roche at 31 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Daratumumab and Lenalidomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 31 sitesUnited States
- Study dates
- 22 Jul 2015to 19 Mar 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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)
Trial locations and contacts
31 sites in 1 country.
31 sites in 1 country
United States31 sites
Univ of Michigan Medical Ctr
Ann Arbor, Michigan, 48109-0718
Emory Univ Winship Cancer Inst
Atlanta, Georgia, 30322
University of Maryland School of Medicine
Baltimore, Maryland, 21201
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Med Ctr; Hem/Onc
Boston, Massachusetts, 02215
UNC Chapel Hill
Chapel Hill, North Carolina, 27514
Medical University of South Carolina; Hollings Cancer Center
Charleston, South Carolina, 29425
Cleveland Clinic Foundation
Cleveland, Ohio, 44915
Texas Oncology-Baylor Sammons Cancer Center
Dallas, Texas, 75246
UT Southwestern MC at Dallas
Dallas, Texas, 75390
Karmanos Cancer Institute.
Detroit, Michigan, 48201
Henry Ford Hospital; Hematology Oncology
Detroit, Michigan, 48202
Indiana University Health; Goshen Center for Cancer Care
Goshen, Indiana, 46526
Comprehensive Cancer Centers of Nevada
Henderson, Nevada, 89014
Houston Methodist Cancer Center
Houston, Texas, 77030
Indiana University Department of Medicine; IU Simon Cancer Center
Indianapolis, Indiana, 46202
Mayo Clinic Hospital - Florida
Jacksonville, Florida, 32224
Scripps Clinic Torrey Pines
La Jolla, California, 92037
University Of Arkansas
Little Rock, Arkansas, 72205
University of Louisville
Louisville, Kentucky, 40202-1798
Loyola University Med Center
Maywood, Illinois, 60153
Yale University
New Haven, Connecticut, 06511
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
UC Davis; Comprehensive Cancer Center
Sacramento, California, 95817
University of California, San Francisco
San Francisco, California, 94116
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: 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.
- Conditions
- Multiple Myeloma
- Being tested
- Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Daratumumab, Lenalidomide, Pomalidomide, Dexamethasone
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibodyDrug
Also called Tecentriq, MPDL3280A, "ATZ"
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.
DaratumumabDrug
Also called Darzalex, "DAR"
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.
LenalidomideDrug
Also called Revlimid, "LEN"
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.
PomalidomideDrug
Also called Pomalyst, "POM"
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.
DexamethasoneDrug
Participants will receive either 20mg or 40mg of dexamethasone PO every 7 days from Day 1 of each cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody |
| 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. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Lenalidomide |
| 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. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Lenalidomide |
| 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. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Daratumumab |
| 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. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Daratumumab |
| 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). Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Daratumumab |
| 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. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Daratumumab; Drug: Lenalidomide |
| 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. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Daratumumab; Drug: Lenalidomide |
| 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. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Daratumumab; Drug: Pomalidomide |
| 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. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Daratumumab; Drug: Pomalidomide |
| 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. Receives: Drug: Daratumumab; Drug: Pomalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants by Best Overall Response According to International Myeloma Working Group (IMWG) Criteria
Measured: 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
Measured: From start of treatment until 30 days after last dose (up to approximately 36 months)
RP2D of Pomalidomide in the Combinations Tested
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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)
Measured: 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
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2015 (estimated)
- Study start22 Jul 2015
- Primary completion19 Mar 2021
- Study completion19 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02431208
- Sponsor's protocol ID
- GO29695
- Status last verified
- Mar 2021
- First submitted
- 27 Apr 2015
- Last updated
- 2 Apr 2021
- Results posted
- No
Publications
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.
PubMed 37559718
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02431208
- Acronym / sponsor ID
- GO29695
- Conditions
- Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 22 Jul 2015 (actual)
- Primary completion
- 19 Mar 2021 (actual)
- Study completion
- 19 Mar 2021 (actual)
- First posted
- 30 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Cohort A: ATZ (Run-In) | Experimental | Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibodyCohort 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 | Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Drug: LenalidomideCohort 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): | Experimental | Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Drug: LenalidomideCohort 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) | Experimental | Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Drug: DaratumumabCohort 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) | Experimental | Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Drug: DaratumumabCohort 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) | Experimental | Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Drug: DaratumumabCohort 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 | Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Drug: Daratumumab, Drug: LenalidomideCohort 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 | Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Drug: Daratumumab, Drug: LenalidomideCohort 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 | Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Drug: Daratumumab, Drug: PomalidomideCohort 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 | Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Drug: Daratumumab, Drug: PomalidomideCohort 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 comparator | Drug: Daratumumab, Drug: Pomalidomide, Drug: DexamethasoneCohort 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibodyAlso: Tecentriq, MPDL3280A, "ATZ"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. | Drug | Cohort A: ATZ (Run-In), Cohort B1: ATZ + LEN (Dose Escalation), Cohort C: ATZ + LEN (Post-ASCT):, Cohort D1: ATZ + DAR (Run-in), Cohort D2: ATZ + DAR (Expansion), Cohort D3: ATZ + DAR (Progressed), Cohort E1: ATZ + DAR + LEN (Dose Escalation), Cohort E2: ATZ + DAR + LEN (Expansion), Cohort F1: ATZ + DAR + POM (Dose Escalation), Cohort F2: ATZ + DAR + POM (Expansion) |
| DaratumumabAlso: Darzalex, "DAR"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. | Drug | Cohort D1: ATZ + DAR (Run-in), Cohort D2: ATZ + DAR (Expansion), Cohort D3: ATZ + DAR (Progressed), Cohort E1: ATZ + DAR + LEN (Dose Escalation), Cohort E2: ATZ + DAR + LEN (Expansion), Cohort F1: ATZ + DAR + POM (Dose Escalation), Cohort F2: ATZ + DAR + POM (Expansion), Cohort F3: DAR + POM + Dexamethasone |
| LenalidomideAlso: Revlimid, "LEN"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. | Drug | Cohort B1: ATZ + LEN (Dose Escalation), Cohort C: ATZ + LEN (Post-ASCT):, Cohort E1: ATZ + DAR + LEN (Dose Escalation), Cohort E2: ATZ + DAR + LEN (Expansion) |
| PomalidomideAlso: Pomalyst, "POM"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. | Drug | Cohort F1: ATZ + DAR + POM (Dose Escalation), Cohort F2: ATZ + DAR + POM (Expansion), Cohort F3: DAR + POM + Dexamethasone |
| DexamethasoneParticipants will receive either 20mg or 40mg of dexamethasone PO every 7 days from Day 1 of each cycle. | Drug | Cohort F3: DAR + POM + Dexamethasone |
Primary outcome
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)
14 secondary outcomes
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)
Maximum Observed Serum Concentration (Cmax) of Atezolizumab
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
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
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2021.
- Derived from this study: PubMed 37559718Wong 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
31 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody, Daratumumab and Lenalidomide in people with Multiple Myeloma, run by Hoffmann-La Roche at 31 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02431208, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2021.