Outpatient and Intermittent Dosing of Elranatamab in Relapsed/Refractory Multiple Myeloma (EMBRACE)

A Study of Elranatamab Management With Outpatient and Intermittent Dosing in Relapsed/Refractory Multiple Myeloma

A phase II study of single agent elranatamab in patients with relapsed and/or refractory multiple myeloma (MM) who have previously received at least three classes of therapeutic agents and are refractory to the last line of treatment. The primary objective of this study is to improve the tolerability and safety of elranatamab in patients with relapsed and/or refractory multiple myeloma by evaluating an outpatient and intermittent dosing strategy.

Study Overview

• Status: Recruiting
• Conditions: Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Elranatamab injection

Detailed Description

This is a multi-centre, single arm, phase II study of single agent elranatamab in patients with relapsed and/or refractory multiple myeloma (MM) who have previously received at least three classes of therapeutic agents and are refractory to the last line of treatment. Potential study participants must have documented evidence of refractory or progressive disease during or within 60 days (measured from the end of the last cycle) of completing treatment with the last anti-myeloma drug regimen used just prior to study entry. Study participants will receive SC administration of elranatamab until disease progression, unacceptable toxicity or death. The primary short term outcome is hospitalization rate within the first 2 weeks of Cycle 1 of treatment; the primary long term outcome is rate of grade 3+ infections within the first 24 months of treatment. Study participants will be followed for survival for 36 months from the date of enrollment. A total of 40 study participants will be enrolled across approximately 5 Canadian clinical trial sites.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Emilio Aguirre, CRA,HIT,CHIM; Phone Number: 42650 905-527-2299; Email: aguirre@mcmaster.ca
• Study Contact Backup: Name: Daryl Solomon; Phone Number: 42622 905-527-2299; Email: solomd5@mcmaster.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1L3
      • Recruiting
      • Vancouver Cancer Center
      • Contact: Christopher Venner, MD; Phone Number: 604-877-6000
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Recruiting
      • Juravinski Cancer Center
      • Contact: Hira Mian, MD; Phone Number: 905-387-9495; Email: hira.mian@medportal.ca
    • Kingston, Ontario, Canada, K7L 2V7
      • Recruiting
      • Kingston General Hospital
      • Contact: Ashlee Young, Trial Activation Coordinator; Phone Number: 613-549-6666; Email: ashlee.young@kingstonhsc.ca
      • Principal Investigator: Bethany Monteith, MD
    • London, Ontario, Canada, N6A 5W9
      • Not yet recruiting
      • London Health Science Centre - Victoria Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • Ottawa Hospital
      • Contact: Arleigh Robertson McCurdy, MD; Phone Number: 71281 613-737-8899

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Relapsed and/or refractory MM defined as:

   1. Documented evidence of progressive disease (PD) after achieving at least minimal response (MR) for ≥ 1 cycle during a previous MM treatment (i.e., relapsed MM).
   2. Disease progression during or within 60 days from the end of the most recent MM treatment (i.e., refractory MM).

2. Measurable disease based on IMWG criteria, defined as at least one of the following, documented within 28 days before enrollment:

   1. Serum M-protein ≥ 0.5 g/dl.
   2. Urine M-protein excretion ≥ 200 mg/24 h.
   3. Serum-free light chains (FLC) assay: Involved FLC level ≥ 10 mg/dl (≥ 100 mg/l) AND an abnormal serum-free light chain ratio (< 0.26 or > 1.65) only for patients without measurable serum or urine M protein.

3. Receipt of at least three prior classes of drugs either in separate regimens or as combinations.

   The three classes are defined as:

   An immunomodulatory drug (lenalidomide or pomalidomide), a proteasome inhibitor (bortezomib, ixazomib, carfilzomib), and an anti-CD38 drug (daratumumab or isatuximab).

4. At least 18 years of age.
5. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.

Exclusion Criteria:

Medical conditions

1. Active plasma cell leukemia (either 20% of peripheral white blood cells or > 2.0 × 109/L circulating plasma cells by standard differential).
2. Amyloidosis.
3. POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, Skin Changes).
4. Monoclonal gammopathy of unknown significance or smoldering multiple myeloma.
5. Solitary plasmacytoma.
6. Stem cell transplant within 12 weeks prior to enrollment or active graft versus host disease.

7. History of prior treatment with a BCMA targeting agent.

   Laboratory Parameters

8. Laboratory results within 28 days as per below prior to enrollment:

   • Absolute neutrophil count (ANC) ≤ 1.0 x 109 /L) (use of growth factor is permitted if completed at least 7 days prior to enrollment).
   • Platelet count ≤ 25 x 109 /L (transfusion support permitted if completed at least 7 days prior to enrollment).
   • Hemoglobin ≤ 8.0 g/dL (transfusion support permitted if completed at least 7 days prior to enrollment, concurrent erythropoietin stimulating agents allowed).
   • Serum AST and ALT > 2.5 x upper limit of normal (ULN).
   • Creatinine clearance < 30 mL/min (according to the Cockcroft Gault formula, by 24-hour urine collection for creatinine clearance, or according to local institutional standard method).
   • Total bilirubin > 2.0 x ULN (≥ 3.0 unless known to have Gilbert's disease).

   Support Requirement

9. As this protocol requires outpatient administration, the patient will be excluded if they cannot agree to the following for the first 9 days post-first dose of drug administration:

   1. Staying within 60 minutes of travel distance to their trial-based hospital.
   2. Must have a caregiver/support person who will stay with the patient.
   3. Patient and/or their caregiver/support person agree to monitor and record oral temperature q8 hours.
   4. Patients must agree that if they have an oral temperature of (≥38°C), they must report to the study team within 1 hour and can come to the hospital for admission within 2 hours.

   Other co-morbidities

10. Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as any of the following within 6 months before enrollment:

    • Acute myocardial infarction or acute coronary syndromes (eg, unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, symptomatic pericardial effusion).
    • Clinically significant cardiac arrhythmias (eg, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia).
    • Thromboembolic or cerebrovascular events (eg, transient ischemic attack, cerebrovascular accident, deep vein thrombosis [unless associated with a central venous access complication], or pulmonary embolism).
    • Prolonged QT syndrome (or triplicate average QTcF >470 msec at screening).
11. Ongoing Grade ≥2 peripheral sensory or motor neuropathy.
12. History of Guillain-Barre Syndrome (GBS) or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
13. Unresolved acute effects of any prior therapy for MM in the last three months to either baseline severity or NCI CTCAE ≤Grade 1.
14. Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection.
15. Any other active malignancy within 2 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
16. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities), or surgical (major surgery within 14 days prior to enrollment) that could interfere with the patient's safety, obtaining informed consent or compliance to the study procedures.

17. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to elranatamab or any of the components of the study treatment.

    Concomitant Medications

18. Treatment with a chemotherapeutic or anti-MM drug within the last 28 days or 5 half-lives (whichever is shorter) prior to enrollment or are currently enrolled in another interventional clinical study.
19. Receipt of any other therapy to treat cancer (including radiation, biologics, cellular therapies, and/or steroids at doses > 20 mg dexamethasone or equivalent) within 14 days prior to the enrollment.

20. Receipt of any live vaccine within 30 days prior to enrollment or expected need of live vaccination during study participation. (Administration of locally approved non-live vaccine can be done as per local guidelines during the screening and/or treatment period including the COVID-19 mRNA vaccine. Elranatamab should be administered ± 7 days from the SARS-CoV-2 vaccine administration).

    Pregnancy and Contraception

21. Pregnancy or lactating female or inability of female patients of childbearing potential (FCBP) to meet contraception requirements (see Section 5.1.3.).

    Informed Consent

22. Inability to provide signed, informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Elranatamab injection; The administration of two step-up elranatamab doses (12 mg and 32 mg) and full dose 76 mg. The dosing interval for the first Cycle (each cycle q28 days) is every week. Cycles 2-3, the dosing interval increases to q2weeks. Cycles 4-12, the dosing interval increases to q4weeks. Cycles 13+, further dosing interval increases to q8weeks will be scheduled if a participant meets criteria for IMWG complete response (CR) in Cycle 12 (bone marrow required at Cycle 12 to confirm). If a participant does not meet CR criteria at Cycle 12, they will be continued on Q4W dosing.

Drug: Elranatamab injection; Elranatamab (Elrexfio) is a humanized bispecific antibody that targets both BCMA-expressing multiple myeloma (MM) cells and CD3-expressing T cells.; Other Names: Elrexio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization rate	Hospitalization rate, defined as the number of patients who are hospitalized within the first 2 weeks of Cycle 1 of treatment, due to any cause, divided by the number of patients who are treated with elranatamab.	2 weeks
Rate of grade 3+ infections	Rate of grade 3+ infections as grade by NCI CTCAE v5 within the first 24 months of treatment, defined as the number of patients who experience a grade 3+ infection within 24 months of treatment, divided by the number of patients who are treated with elranatamab.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate.	Overall response rate, defined by the IMWG criteria.	36 months
Progression free survival.	PFS, defined as the time from the date of first dose until confirmed PD per IMWG criteria or death due to any cause, whichever occurs first.	36 months
Duration of response.	DOR is defined, for participants with an overall response per IMWG criteria, as the time from the first documentation of overall response that is subsequently confirmed, until confirmed PD per IMWG criteria, or death due to any cause, whichever occurs first.	36 months
Time to response.	TTR is defined, for participants with an overall response per IMWG criteria, as the time from the date of first dose to the first documentation of overall response that is subsequently confirmed.	36 months
Adverse Events	AEs will be graded according to NCI CTCAE Version 5. CRS and ICANS will be assessed. AEs will be characterized by type, frequency, severity, timing, seriousness, and relationship to elranatamab. AEs will be presented with and without regard to causality based on the investigator's judgment. The frequency of overall toxicity, categorized by toxicity Grades 1 through 5, will be described. Additional summaries will be provided for AEs that are observed with higher frequency and for AESIs (including CRS and ICANS).	36 months
Clinical laboratory data	Clinical laboratory data will be classified by grade according to NCI CTCAE version 5.0 and will be analyzed using summary statistics. The worst on-treatment grades during the treatment period will be summarized.	36 months.
Overall survival	OS, defined from the date of study registration to the date or death due to any cause.	36 months
Patient Frailty	Frailty will be measured using the IMWG frailty score and the time for the 4-meter walk test will be recorded.	To the time of disease progression.
Frequency and Timing of Hospitalization	Frequency and timing hospitalization will be recorded during the first two weeks of the study treatment.	2 weeks.
Patient Quality of Life	QoL during treatment measured using the EORTC QOL Questionnaire-C30 instrument EORTC QLQ-C30	To the time of disease progression.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory outcome BCMA expression (biologic tumor characteristics)	BCMA levels in blood and their relationship to clinical response and progression.	36 months
Feasibility, adherence and satisfaction of remote patient monitoring	Feasibility, adherence and satisfaction of remote patient monitoring during the first 9 days of treatment using an outpatient remote monitoring device	First 9 days of treatment.
Patient satisfaction with the use of the remote monitoring device	Patient satisfaction with the use of the remote monitoring device will be captured using a single, 5-point likert scale question, asked when the device is returned.	First 9 days of treatment.

Collaborators and Investigators

• Sponsor: Ontario Clinical Oncology Group (OCOG)
• Collaborators: Pfizer; McMaster University
• Investigators: Principal Investigator: Hira Mian, MD, McMaster University; Study Director: Jim Wright, MD, OCOG - McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 11, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 20, 2024

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: relapsed; refractory; cytokine release syndrome; multiple myeloma; elranatamab; immune effector-cell associated neurotoxicity
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Systemic Inflammatory Response Syndrome; Inflammation; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Shock; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Cytokine Release Syndrome; Recurrence; Multiple Myeloma
• Other Study ID Numbers: OCOG-2023-EMBRACE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No