Clinical trial NCT05014412: A Study to Learn About the Study Medicine (Elranatamab) in Participants With Multiple Myeloma That Has Come Back After Responding to Treatment or Has Not Responded to Treatment
Official title: A PHASE 1/2, OPEN-LABEL, MULTICENTER STUDY TO EVALUATE A DOSING REGIMEN WITH TWO STEP-UP PRIMING DOSES AND LONGER DOSING INTERVALS OF ELRANATAMAB (PF-06863135) MONOTHERAPY IN PARTICIPANTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: BCMA
Multiple Myeloma
Relapse/Refractory
RRMM
Elranatamab
Targeted T-cell
MagnetisMM
MM9
Phase 2
B-Cell Maturation Antigen
monoclonal antibody
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-08-20
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study (Part 1 and Part 2) is to evaluate the safety of a step-up dosing approach (starting with low doses followed by higher doses) of the study medicine (elranatamab) in participants with multiple myeloma that has come back after responding to treatment or has not responded to treatment (relapsed/refractory multiple myeloma). This study will also look at the safety and efficacy of different doses of elranatamab, as well as different intervals between doses.

Participants in the study will receive elranatamab as an injection under the skin at the study clinic. After the initial step-up doses, participants will start receiving one dose every week. The frequency of clinic visits for injections may then decrease over time. Participation will be at least two years.

Detailed description: The purpose of the study (Part 1 and Part 2) of the study is to evaluate the safety (in particular the rate of Grade ≥ 2 CRS) of a step-up priming dose regimen of elranatamab in participants with relapsed/refractory multiple myeloma. In addition, this study will assess the safety of different dosing regimens of elranatamab and if it can provide a clinical benefit in those participants. Elranatamab is a bispecific antibody: binding of elranatamab to CD3-expressing T-cells and BCMA-expressing multiple myeloma cells causes targeted T-cell-mediated cytotoxicity.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of multiple myeloma (IMWG criteria, Rajkumar et al, 2014)
* Measurable disease, as defined by at least 1 of the following:

  1. Serum M-protein \>0.5 g/dL by SPEP
  2. Urinary M-protein excretion \>200 mg/24 hours by UPEP
  3. Serum immunoglobulin FLC≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio
* Refractory to at least one IMiD
* Refractory to at least one PI
* Refractory to at least one anti-CD38 antibody
* Relapsed/refractory to last anti-myeloma regimen
* ECOG performance status ≤1
* 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
* Active Plasma cell leukemia
* POEMS syndrome
* Amyloidosis
* Waldenström's macroglobulinemia
* Known active CNS involvement or clinical signs of myelomatous meningeal involvement
* Stem cell transplant within 12 weeks prior to enrollment or active GVHD
* Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection
* 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 malignancy with minimal risk of recurrence per investigator.
* Previous treatment with an anti-BCMA bispecific antibody or CAR-T cell therapy.
* Live attenuated vaccine within 4 weeks of the first dose
* Previous administration with an investigational drug within 30 days or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer)
* Known or suspected hypersensitivity to the study intervention, or any of its excipients

Primary outcomes:
measure: Number of Participants With Grade 2 or Higher Cytokine Release Syndrome (CRS) During Cycle 1: Parts 1 and 2
timeFrame: Parts 1 and 2: Cycle 1 (28 days)
Secondary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs): Part 2A
timeFrame: Part 2A: 28 days starting from the first 116 or 152 mg dose
measure: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [All Causalities and Treatment Related]: Parts 1 and 2
timeFrame: Day 1 of dosing up to 90 days post last dose (maximum treatment duration 25 cycles, follow up to 790 days)
measure: Number of Participants With Maximum Grade 3 or 4 and Grade 5 AEs [All Causalities and Treatment Related] Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5: Parts 1 and 2
timeFrame: Day 1 of dosing up to 90 days post last dose (maximum treatment duration 25 cycles, follow up to 790 days)
measure: Number of Participants With Adverse Events of Special Interest (AESI)- CRS and Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) [All Causalities and Treatment Related]: Parts 1 and 2
timeFrame: Day 1 of dosing up to 90 days post last dose (maximum treatment duration 25 cycles, follow up to 790 days)
measure: Number of Participants With Hematological Measures With Baseline CTCAE Grade >=2 Shifted to a Maximum CTCAE Grade 3-4: Parts 1 and 2
timeFrame: Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
measure: Number of Participants With Clinical Chemistry Parameters With Baseline CTCAE Grade >=2 Shifted to a Maximum CTCAE Grade 3-4: Parts 1 and 2
timeFrame: Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
measure: Number of Participants With Liver Function Tests Abnormalities: Parts 1 and 2
timeFrame: Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
measure: Objective Response Rate (ORR) Per International Myeloma Working Group (IMWG) Response Criteria as Determined by Investigator: Parts 1 and 2
timeFrame: Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
measure: Complete Response Rate (CRR) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2
timeFrame: Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
measure: Time to Response (TTR) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2
timeFrame: Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
measure: Duration of Response (DOR) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2
timeFrame: Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
measure: Duration of Complete Response Rate (DOCR) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2
timeFrame: Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
measure: Progression Free Survival (PFS) Per IMWG Response Criteria as Determined by Investigator: Parts 1 and 2
timeFrame: Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
measure: Overall Survival (OS): Parts 1 and 2
timeFrame: Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
measure: Minimal Residual Disease (MRD) Negativity Rate Per IMWG Sequencing Criteria: Parts 1 and 2
timeFrame: Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
measure: Pre- and Post-dose Concentrations of Elranatamab: Parts 1 and 2
timeFrame: Parts 1 and 2: Till study completion approximately 3 years 7 months
measure: Number of Participants With Anti-Drug Antibody (ADA) and Neutralizing Antibody (Nab) Against Elranatamab: Parts 1 and 2
timeFrame: Parts 1 and 2: From start of treatment to end of the study (approximately 3 years 7 months)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Fort Collins
country: United States
facility: Cancer Care & Hematology - Fort Collins
state: Colorado
city: Greeley
country: United States
facility: UCHealth Cancer Care & Hematology - Greeley
state: Colorado
city: Loveland
country: United States
facility: UCHealth Cancer Care & Hematology - Loveland
state: Colorado
city: Gainesville
country: United States
facility: UF Health Shands Cancer Hospital
state: Florida
city: Gainesville
country: United States
facility: UF Health Shands Hospital Pharmacy Investigational Drug Service - Main
state: Florida
city: Gainesville
country: United States
facility: UF Health Shands Hospital
state: Florida
city: Metairie
country: United States
facility: East Jefferson General Hospital Bone Marrow Transplant Clinic
state: Louisiana
city: Metairie
country: United States
facility: East Jefferson General Hospital
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Montvale
country: United States
facility: MSK Bergen
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - David H. Koch Center for Cancer Care (74th Street).
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: MSK Nassau
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Austin
country: United States
facility: St. David's South Austin Medical Center
state: Texas
city: San Antonio
country: United States
facility: Blood Cancer and Stem Cell Transplant Clinic
state: Texas
city: San Antonio
country: United States
facility: Methodist Healthcare System of San Antonio dba Methodist Hospital
state: Texas
city: San Antonio
country: United States
facility: Methodist Hospital Investigational Pharmacy
state: Texas
city: San Antonio
country: United States
facility: Methodist Plaza Clinical Trials Office
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Kobe-city
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Shibuya-ku
country: Japan
facility: Japanese Red Cross Medical Center
state: Tokyo
city: Kyoto
country: Japan
facility: University Hospital,Kyoto Prefectural University of Medicine
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust NIHR
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: