Multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
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 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 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 transplant-ineligible as defined by age =65 years) yes F.1.3.1 Number of subjects for this age range 639
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions: 1. Smoldering MM or MGUS or Waldenströms Macroglobulinemia or Plasma cell leukemia as defined as =20 % circulating plasma cells in the peripheral blood with an absolute plasma cell count of more than 2x10 9/L or Systemic light chain amyloidosis or POEMS Syndrome. 2. Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as any of the following within 6 months prior to enrollment: a. Acute myocardial infarction or acute coronary syndromes (eg, unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, symptomatic pericardial effusion); b. Clinically significant cardiac arrhythmias (eg, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia); c. Thromboembolic or cerebrovascular events (eg, transient ischemic attack, cerebrovascular accident, deep vein thrombosis [unless associated with a central venous access complication] or pulmonary embolism); d. Prolonged QT syndrome (or QTcF >470 msec at screening). e. LVEF 3 peripheral motor polyneuropathy. 4. Participants with active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) COVID-19/SARS-CoV-2, HBV, HCV, and known HIV or AIDS-related illness. Active infections must be resolved at least 14 days prior to enrollment. Comments regarding specific circumstances follow. a. HIV: In equivocal cases, participants whose viral load is negative may be eligible. HIV seropositive participants who are otherwise healthy and at low risk for AIDS-related outcomes could be considered eligible. Potential eligibility for a specific HIV positive protocol candidate should be evaluated and discussed with the Sponsor prior to any screening, based on current and past CD4 and T-cell counts, history (if any) of AIDS defining conditions (eg, opportunistic infections), and status of HIV treatment. Also, the potential for drug-drug interactions will be taken into consideration. b. HBV/HCV: Relevant laboratory tests should be performed at screening. Refer to CDC website (https://www.cdc.gov/hepatitis/index.htm) for further details. c. HBV: • This criterion excludes participants with a positive HBsAg (ie, either acute or chronic active hepatitis). • However, participants with HBV antibody positivity indicating immunity, either due to vaccination or prior natural infection, are eligible. • Participants with positive anti-HBcAb but negative HBsAg and anti-HBsAb profile are eligible if HBV DNA is not detected. d. HCV: • Positive HCV antibody is indicative of infection but may not necessarily render a potential participant ineligible, depending on clinical circumstances. If exposure to HCV is recent, HCV antibody may not have yet turned positive. In this circumstance it is recommended to test HCV RNA. Refer to CDC website for further details (https://www.cdc.gov/hepatitis/hcv/pdfs/hcv_graph.pdf). 5. 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. 6. Participants with known or suspected hypersensitivity to the study interventions or any of their excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 • To assess 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 •To evaluate the efficacy of Arm A and Arm B •To determine the safety and tolerability of elranatamab when used in combination with daratumumab + lenalidomide •To evaluate the PK of elranatamab when used in combination with daratumumab + lenalidomide •To evaluate the immunogenicity of elranatamab when used in combination with daratumumab and lenalidomide . •To evaluate the impact of treatment on participant HRQoL;Primary end point(s): Part 1 •DLTs during the DLT observation period (from the first dose of elranatamab in Cycle 0 until the end of Cycle 1). Part 2 • MRD negativity rate at 12 months after randomization per IMWG as assessed via NGS • PFS by investigator 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 • AEs as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), timing, seriousness, and relationship to study treatment. Severity of CRS and ICANS will be graded according to ASTCT criteria. • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0), and timing. • ORR and CRR, per IMWG response criteria as determined by investigator. • Time to event endpoints: TTR, DOR, DOCR and PFS per IMWG response criteria as determined by investigator, and OS; • MRD negativity rate (central laboratory) per IMWG sequencing criteria. • Predose and post dose concentrations of elranatamab • ADAs and NAbs against elranatamab • Predose concentrations of daratumumab and lenalidomide Part 2 • Overall MRD negativity rate per IMWG • Duration of MRD negativity per IMWG • Sustained MRD negativity rate per IMWG • ORR, CRR, TTR, DOR, and DOCR by investigator per IMWG • OS • 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 and MY20;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 | — |
Countries
Australia, Austria, Belgium, Czechia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Korea, Republic of, Netherlands, Poland, Spain, Taiwan
Contacts
Public ContactClinicalTrials.gov Call Center
Pfizer Inc.
Outcome results
None listed