A Study to Learn About the Effects of the Combination of Elranatamab (PF-06863135), Daratumumab, and Lenalidomide Compared With Daratumumab, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Who Are Not Candidates for Transplant

JRCT ID: jRCT2021220036

Registered date:26/12/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Multiple Myeloma
• Date of first enrollment: 12/06/2023
• Target sample size: 646
• Countries of recruitment: Korea, Republic of,Japan,Poland,Japan,Taiwan,Japan
• Study type: Interventional

Intervention(s)

Part 1 Dose Level 1:Elranatamab, Daratumumab, Lenalidomide
Part 1 Multiple Dose Levels :Elranatamab, Daratumumab, Lenalidomide
Part 2 Randomized Arm A:Elranatamab, Daratumumab,Lenalidomide
Part 2 Randomized Arm B: Daratumumab, Lenalidomide, Dexamethasone

Outcome(s)

Primary Outcome

Primary Outcome Measures :
1.Part 1 Dose Limiting Toxicity [ Time Frame: From the first dose of elranatamab up until the end of Cycle 1 (each Cycle is 28 days). ]
2.Part 2: Progression free survival [ Time Frame: From randomization up to 61 months. ]
3.Part 2: Minimal residual disease negativity rate [ Time Frame: At 12 months after randomization ]

Secondary Outcome

Secondary Outcome Measures :
1.Overall minimal residual disease negativity rate [ Time Frame: From date of randomization up to 61 months ]
2.Duration of minimal residual disease negativity (Part 2) [ Time Frame: From date of minimal residual disease negative status up to 61 months ]
3.Sustained minimal residual disease negativity rate (Part 2) [ Time Frame: From date of randomization up to 61 months ]
4.Objective Response Rate [ Time Frame: From the date of randomization up to 61 months ]
5.Complete Response Rate [ Time Frame: From the date of randomization up to 61 months ]
6.Time to Response [ Time Frame: From the date of randomization to date of confirmed objective response up to 61 months ]
7.Duration of Response [ Time Frame: From the date of confirmed objective response up to 61 months ]
8.Duration of Complete Response [ Time Frame: From the date of confirmed complete response up to 61 months ]
9.Overall Survival [ Time Frame: From date of randomization up to 61 months ]
10.Frequency of treatment-emergent adverse events [ Time Frame: From the date of first dose of study intervention up to 61 months ]
11.Frequency of abnormal laboratory results [ Time Frame: From the date of first dose of study intervention up to 61 months ]
12.Elranatamab pharmacokinetics by pre-dose concentrations when used with lenalidomide and daratumumab [ Time Frame: From date of first dose of study intervention up to 61 months ]
Pharmacokinetics of elranatamab (trough concentrations of elranatamab)

13.Elranatamab pharmacokinetics by post-dose concentrations when used with lenalidomide and daratumumab [ Time Frame: From date of first dose of study intervention up to 61 months ]
Pharmacokinetics of elranatamab (post-dose serum concentrations of elranatamab)

14.Incidence of Anti-Drug Antibody and Neutralizing Antibody against elranatamab [ Time Frame: From date of first dose of study intervention up to 61 months ]
Immunogenicity of elranatamab

15.Titers of Anti-Drug Antibody and Neutralizing Antibody against elranatamab [ Time Frame: From date of first dose of study intervention up to 61 months ]
Immunogenicity of elranatamab

16.Part 2: Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire -Myeloma 20 [ Time Frame: From date the informed consent is signed up to 61 months ]
Higher scores on the functioning subscales (body image, future perspective) represent higher levels of functioning, whereas higher scores on the symptom subscales (disease symptoms, side effects) represent a greater presence of symptoms

17.Part 2: Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 [ Time Frame: From date the informed consent is signed up to 61 months ]
Higher scores on the functional scales represent higher levels of functioning. Higher scores on the global health status/quality of life scale represent higher health status/quality of life. Higher scores on the symptom scales/items represent a greater presence of symptoms.

18.Part 1: Daratumumab and lenalidomide pharmacokinetics by pre-dose concentrations in combination with elranatamab [ Time Frame: From date of first dose of study intervention up to 61 months ]
Pharmacokinetics of daratumumab and lenalidomide (trough concentrations of daratumumab and lenalidomide)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Inclusion Criteria:
*Diagnosis of multiple myeloma (MM) as defined by IMWG criteria (Rajkumar et al., 2014)
*Measurable disease based on IMWG criteria as defined by at least 1 of the following:
*Serum M-protein >=0.5 g/dL;
*Urinary M-protein excretion >=200 mg/24 hours;
*Involved FLC >=10 mg/dL (>=100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
*Part 1: Participants with relapsed/refractory multiple myeloma (RRMM) who have received 1-2 prior lines of therapy including at least one immunomodulatory drug and one proteasome inhibitor: or participants with newly-diagnosed multiple myeloma (NDMM) that are transplant-ineligible as defined by age >=65 years or transplant-ineligible as defined by age <65 years with comorbidities impacting the possibility of transplant.
*Part 2: participants with newly-diagnosed multiple myeloma that are transplant-ineligible as defined by age >=65 years or transplant-ineligible as defined by age <65 years with comorbidities impacting the possibility of transplant
*ECOG performance status <=2.
*Not pregnant and willing to use contraception
*For participants with RRMM: Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade <=1.

Exclude criteria

Exclusion Criteria:
*Smoldering Multiple Myeloma.
*Monoclonal gammopathy of undetermined significance.
*Waldenstroms Macroglobulinemia
*Plasma cell leukemia.
*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.
*Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ, or Stage 0/1 with minimal risk of recurrence per investigator.
*For participants with RRMM: Previous treatment with a BCMA-directed therapy or anti-CD38-directed therapy within 6 months preceding the first dose of study intervention in this study. Stem cell transplant <=3 months prior to first dose of study intervention or active GVHD.
*For participants with NDMM: Previous systemic treatment for MM except for a short course of corticosteroids (ie, up to 4 days of 40 mg dexamethasone or equivalent before the first dose of study intervention).
*Live attenuated vaccine administered within 4 weeks of the first dose of study intervention.
*Administration of investigational product (eg, drug or vaccine) concurrent with study intervention or within 30 days (or as determined by the local requirement) preceding the first dose of study intervention used in this study.

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT05623020