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A Study to Learn About the Study Medicine Elranatamab Alone and With Daratumumab in People With Multiple Myeloma Who Have Received Other Treatments

Phase 3
Recruiting
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT05020236
Lead Sponsor
Pfizer
Brief Summary

The purpose of this clinical trial is to (1) learn whether the BCMA-CD3 bispecific antibody elranatamab can provide more benefit to people with multiple myeloma compared to a combination therapy including daratumumab, pomalidomide, and dexamethasone, and (2) learn about the safety and activity of elranatamab in combination with the anti-CD38 monoclonal antibody daratumumab. People with multiple myeloma who have received previous treatment including lenalidomide will be enrolled in the study.

Part 1 of the study will assess the safety and activity of different doses of elranatamab in combination with daratumumab.

People participating in Part 2 of the study will be randomly assigned to receive either elranatamab alone, elranatamab plus daratumumab, or daratumumab, pomalidomide, and dexamethasone. Part 2 will evaluate the safety and activity of (1) elranatamab alone compared to daratumumab, pomalidomide, and dexamethasone, and (2) elranatamab plus daratumumab.

Part 3 will assess the effect of increased measures to protect against infection in people treated with either elranatamab alone or together with daratumumab.

All people participating in the study will receive study treatment until their disease progresses, they experience unacceptable side effects, or they choose to no longer participate in the study.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
944
Inclusion Criteria
  • Prior diagnosis of multiple myeloma 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.
    • Serum immunoglobulin FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
  • Prior anti-multiple myeloma therapy including treatment with lenalidomide.

  • ECOG performance status ≤2.

  • Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.

  • Not pregnant and willing to use contraception.

Exclusion Criteria
  • Smoldering multiple myeloma.
  • Plasma cell leukemia.
  • Amyloidosis.
  • POEMS Syndrome.
  • Stem cell transplant within 12 weeks prior to enrolment, or active graft versus host disease.
  • Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection.
  • Any other active malignancy within 3 years prior to enrolment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
  • Previous treatment with a BCMA-directed therapy.
  • Live attenuated vaccine within 4 weeks of the first dose of study intervention.
  • Administration with an investigational product (e.g. drug or vaccine) concurrent with study intervention or within 30 days preceding the first dose of study intervention used in this study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
Part 1 Safety Lead-In Dose Escalation: Elranatamab + DaratumumabElranatamab-
Part 1 Safety Lead-In Dose Escalation: Elranatamab + DaratumumabDaratumumab-
Part 2 Randomized Arm A: ElranatamabElranatamab-
Part 2 Randomized Arm B: Elranatamab + DaratumumabElranatamab-
Part 2 Randomized Arm B: Elranatamab + DaratumumabDaratumumab-
Part 2 Randomized Arm C: Daratumumab + Pomalidomide + DexamethasoneDaratumumab-
Part 2 Randomized Arm C: Daratumumab + Pomalidomide + DexamethasonePomalidomide-
Part 2 Randomized Arm C: Daratumumab + Pomalidomide + DexamethasoneDexamethasone-
Part 3 Arm D: ElranatamabElranatamab-
Part 3 Arm E: Elranatamab + DaratumumabElranatamab-
Part 3 Arm E: Elranatamab + DaratumumabDaratumumab-
Primary Outcome Measures
NameTimeMethod
Part 1 Safety Lead-In: Incidence of dose limiting toxicitiesFirst 42 days after first elranatamab dose
Part 2 Randomized: Progression free survival per International Myeloma Working Group criteriaFrom date of randomization to date of progressive disease, discontinuation from the study, death, or censoring, whichever occurs first, assessed up to 51 months
Part 3: Frequency of treatment-emergent adverse eventsFirst 84 days after first elranatamab dose
Secondary Outcome Measures
NameTimeMethod
Overall survivalFrom date of randomization to date of discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months
Time to response per International Myeloma Working Group criteriaFrom date of randomization to date of confirmed objective response, assessed up to 51 months
Progression free survival on next-line treatment per International Myeloma Working Group criteriaFrom date of randomization to date of second objective disease progression, discontinuation from the study, death, or censoring, whichever occurs first, assessed up to 51 months
Frequency of treatment-emergent adverse eventsFrom date of first dose of study intervention through minimum of 90 days after last study intervention administration. Reporting of non-serious AEs ends at start of new anti-cancer therapy.
Frequency of abnormal laboratory resultsFrom date of first dose of study intervention through minimum of 90 days after last study intervention administration. Reporting of non-serious AEs ends at start of new anti-cancer therapy.
Daratumumab pharmacokinetics by pre-dose concentrationsFrom date of first dose through up to 14 days after date of last dose of daratumumab
Part 1 Safety Lead-In: Progression free survival per International Myeloma Working Group criteriaFrom date of randomization to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months
Objective response rate per International Myeloma Working Group criteriaFrom date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first, assessed up to 51 months
Complete response rate per International Myeloma Working Group criteriaFrom date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first, assessed up to 51 months
Minimal residual disease negativity rate per International Myeloma Working Group criteriaFrom date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first, assessed up to 51 months
Rate of Grade ≥2 cytokine release syndromeFirst 28 days after first elranatamab dose
Elranatamab immunogenicity by anti-drug antibodies against elranatamabFrom date of first dose through up to 14 days after date of last dose of elranatamab
Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Myeloma 20From date of informed consent through up to 35 days after date of last dose of study intervention
Duration of response per International Myeloma Working Group criteriaFrom date of confirmed objective response to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months
Duration of complete response per International Myeloma Working Group criteriaFrom date of confirmed complete response to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months
Sustained minimal residual disease negativity rate per International Myeloma Working Group criteriaFrom date of randomization to date of progressive disease, discontinuation from study, death, or start of new anticancer therapy, whichever occurs first, assessed up to 51 months
Elranatamab pharmacokinetics by pre- and post-dose concentrationsFrom date of first dose through up to 14 days after date of last dose of elranatamab
Health-related quality of life by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30From date of informed consent through up to 35 days after date of last dose of study intervention

Trial Locations

Locations (236)

Clovis Community Medical Center

🇺🇸

Clovis, California, United States

Community Cancer Institute

🇺🇸

Clovis, California, United States

University of California San Francisco

🇺🇸

Fresno, California, United States

Community Regional Medical Center

🇺🇸

Fresno, California, United States

UCHealth Poudre Valley Hospital

🇺🇸

Fort Collins, Colorado, United States

UCHealth Harmony

🇺🇸

Fort Collins, Colorado, United States

UCHealth Greeley Hospital

🇺🇸

Greeley, Colorado, United States

UCHealth - Medical Center of the Rockies

🇺🇸

Loveland, Colorado, United States

Sylvester Comprehensive Cancer Center - Aventura

🇺🇸

Aventura, Florida, United States

Sylvester Comprehensive Cancer Center- The Lennar Foundation Medical Center

🇺🇸

Coral Gables, Florida, United States

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Clovis Community Medical Center
🇺🇸Clovis, California, United States

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