AN OPEN-LABEL, 3-ARM, MULTICENTER, RANDOMIZED PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ELRANATAMAB (PF-06863135) MONOTHERAPY AND ELRANATAMAB + DARATUMUMAB VERSUS DARATUMUMAB + POMALIDOMIDE + DEXAMETHASONE IN PARTICIPANTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA WHO HAVE RECEIVED AT LEAST 1 PRIOR LINE OF THERAPY INCLUDING LENALIDOMIDE AND A PROTEASOME INHIBITOR

Official 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.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: FACTORIAL
• Masking: NONE
• Enrollment: 944 participants

Study Arms

• Part 1 Safety Lead-In Dose Escalation: Elranatamab + Daratumumab (EXPERIMENTAL)
• Part 2 Randomized Arm A: Elranatamab (EXPERIMENTAL)
• Part 2 Randomized Arm B: Elranatamab + Daratumumab (EXPERIMENTAL)
• Part 2 Randomized Arm C: Daratumumab + Pomalidomide + Dexamethasone (ACTIVE_COMPARATOR)
• Part 3 Arm D: Elranatamab (EXPERIMENTAL)
• Part 3 Arm E: Elranatamab + Daratumumab (EXPERIMENTAL)

Interventions

• DRUG: Elranatamab — subcutaneous
• DRUG: Daratumumab — Daratumumab / hyaluronidase, subcutaneous
• DRUG: Pomalidomide — oral
• DRUG: Dexamethasone — oral

Primary Outcomes

• Part 1 Safety Lead-In: Incidence of dose limiting toxicities (First 42 days after first elranatamab dose)
• Part 2 Randomized: Progression free survival per International Myeloma Working Group criteria (From 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 events (First 84 days after first elranatamab dose)

Secondary Outcomes

• Part 1 Safety Lead-In: Progression free survival per International Myeloma Working Group criteria (From date of randomization to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months)
• Overall survival (From date of randomization to date of discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months)
• Objective response rate per International Myeloma Working Group criteria (From 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)
• Duration of response per International Myeloma Working Group criteria (From date of confirmed objective response to date of progressive disease, discontinuation from study, death, or censoring, whichever occurs first, assessed up to 51 months)
• Time to response per International Myeloma Working Group criteria (From date of randomization to date of confirmed objective response, assessed up to 51 months)

Eligibility Criteria

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.

Trial Locations

• Clovis Community Medical Center, Clovis, California, United States
• Community Regional Medical Center, Fresno, California, United States
• UCHealth Poudre Valley Hospital, Fort Collins, Colorado, United States
• UCHealth Greeley Hospital, Greeley, Colorado, United States
• Sylvester Comprehensive Cancer Center - Aventura, Aventura, Florida, United States
• Sylvester Comprehensive Cancer Center - Coral Springs, Coral Springs, Florida, United States
• University of Miami Hospital and Clinics - Deerfield Beach, Deerfield Beach, Florida, United States
• Sylvester Comprehensive Cancer Center - Hollywood, Hollywood, Florida, United States
• University of Miami Hospital and Clinics, Miami, Florida, United States
• Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street)., New York, New York, United States
• ...and 10 more locations

Contact Information

• Pfizer CT.gov Call Center — CONTACT
  Phone: 1-800-718-1021
  Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Officials

• Pfizer CT.gov Call Center — STUDY_DIRECTOR
  Pfizer

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