Multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants must meet the following inclusion criteria to be eligible for enrollment into the study. Criteria are for both Part 1 and Part 2 unless otherwise specified: Age and Sex: 1. Participant’s age =18 years (or the minimum country specific age of consent if >18) at Visit 1 (Screening). • Male participants and female participants of childbearing potential must agree to use methods of contraception as described in Section 5.3.1. • A female participant is eligible to participate if she is not pregnant or breastfeeding. • Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants. Type of Participant and Disease Characteristics: 2. Diagnosis of multiple myeloma (MM) as defined according to IMWG criteria (Rajkumar et al, 2014), including measurable disease based on IMWG criteria as defined by at least 1 of the following (as assessed by the central laboratory for Part 2): o Serum M-protein =0.5 g/dL; o Urinary M-protein excretion =200 mg/24 hours; o Involved free light chain (FLC) =10 mg/dL (=100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (1.65). 3. Part 1 only: Participant with NDMM or RRMM. NDMM participant must be transplant-ineligible as defined by age =65 years or transplantineligible as defined by age =65 years) yes F.1.3.1 Number of subjects for this age range 1100
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions: •Smoldering MM. •Monoclonal gammopathy of undetermined significance (MGUS). •Plasma cell leukemia. •Waldenströms Macroglobulinemia. •Systemic light chain amyloidosis. •Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin abnormalities (POEMS) Syndrome. •Impaired cardiovascular function or clinically significant cardiovascular diseases within 6 months prior to enrollment. •Ongoing Grade 3 or higher peripheral sensory or motor neuropathy, history of Guillain-Barré syndrome (GBS) or GBS variants, or history of any Grade >3 peripheral motor polyneuropathy. •Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) coronavirus disease 2019 (COVID-19)/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hepatitis B virus (HBV), hepatitis C virus (HCV), and known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. Active infections must be resolved at least 21 days prior to enrollment. Participants treated with systemic anti-infective agents within 28 days prior to enrollment are not eligible. Prophylactic use of systemic agents is permitted. •Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ, or Stage 0/1 with minimal risk of recurrence per investigator. •Participants with known or suspected hypersensitivity to the study interventions or any of their excipients. •Participants with known or suspected central nervous system (CNS) or clinical signs of myelomatous meningeal involvement. •Other surgical (including major surgery within 14 days prior to enrollment), medical or psychiatric conditions including recent (within the past year) or active suicidal ideation/behaviour or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. •Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed (assuming no drug interaction potential).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 • To assess dose limiting toxicities (DLTs) of EDR to select an RP3D for the combination to be used in Part 2 of this study. Part 2 •To compare the efficacy of EDR (Arm A) vs DRd (Arm B) as measured by MRD status and PFS ;Secondary Objective: Part 1 •To evaluate the overall safety profile of EDR to select an RP3D for the combination to be used in Part 2 of this study. •To evaluate the efficacy of EDR to select an RP3D for the combination to be used in Part 2 of this study. •To evaluate the PK of elranatamab when used in combination with daratumumab and lenalidomide •To evaluate the immunogenicity of elranatamab when used in combination with daratumumab and lenalidomide •To evaluate the PK of daratumumab and lenalidomide when used in combination with elranatamab Part 2 Key Secondary: To compare the efficacy of EDR (Arm A) vs DRd (Arm B) as measured by OS;Primary end point(s): Part 1 DLTs during the DLT observation period: •For all dose levels (DLs) except DL F: From the first priming dose of elranatamab in the 2 Step-up Priming Dose Period until 28 days (± visit windows) from the first administration of the EDR combination. •For DL F: 28 days (± visit windows) from the day of the first full dose of elranatamab (76 mg) in combination with daratumumab (D) and lenalidomide (R.). Part 2: •Sustained MRD negativity rate (central lab) for at least 12 months per IMWG as assessed via next generation sequencing (NGS) •PFS by blinded independent central review (BICR) per IMWG;Timepoint(s) of evaluation of this end point: Assessments are to be conducted at the time points specified in the Schedule of Activity (SoA) in Section 1 of the protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 •Adverse events (AEs) as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0), timing, seriousness, and relationship to study treatment. Severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria. • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing. •Objective response rate (ORR) and complete response rate (CRR,), per International Myeloma Working Group (IMWG) response criteria as determined by investigator. •Time to event endpoints: time to response (TTR, ), duration of response (DOR, ), duration of complete response (DOCR) and progression-free survival (PFS) per IMWG response criteria as determined by investigator, and overall survival (OS;); •Minimal residual disease (MRD) negativity rate (central laboratory) per IMWG sequencing criteria. • Predose and post dose concentrations of elranatamab • Anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) against elranatamab • Predose concentrations of daratumumab and lenalidomide Part 2 Key Secondary: OS Secondary: • Overall MRD negativity rate per IMWG • Duration of MRD negativity per IMWG • PFS and progression-free survival on next line of therapy (PFS2) by investigator per IMWG • ORR, CRR, TTR, DOR, and DOCR by BICR per IMWG • AEs as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study treatment. The severity of CRS and ICANS will be graded according to ASTCT criteria (Lee, 2019). • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing. • Predose and post dose concentrations of elranatamab. • ADAs and NAbs against elranatamab. • EORTC QLQ-C30 an | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Mexico, Netherlands, New Zealand, Norway, Poland, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactClinicalTrials.gov Call Center
Pfizer Inc.
Outcome results
None listed