## Protocol Section
### Identification Module
**NCT ID:** NCT06421675

**Acronym:** EMBRACE

**Brief Title:** Outpatient and Intermittent Dosing of Elranatamab in Relapsed/Refractory Multiple Myeloma

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

#### Organization Study ID Info
**ID:** OCOG-2023-EMBRACE
#### Organization
**Class:** OTHER
**Full Name:** Ontario Clinical Oncology Group (OCOG)
### Status Module
#### Completion Date
**Date:** 2028-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-03-11
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Pfizer

#### Lead Sponsor

**Class:** OTHER

**Name:** Ontario Clinical Oncology Group (OCOG)

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** 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.

**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.

### Conditions Module

**Conditions:**

- Refractory Multiple Myeloma

**Keywords:**

- relapsed

- refractory

- multiple myeloma

- elranatamab

- cytokine release syndrome

- immune effector-cell associated neurotoxicity

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** Multi-center, single-arm, phase II study of single-agent elranatamab in patients with relapsed and/or refractory multiple myeloma.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 40

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** The administration of two step-up elranatamab doses (12 mg and 32 mg) and full dose 76 mg. The dosing interval for the first 6 cycles (each cycle q28 days) is every week, cycles 7-12 are bi-weekly. The dosing interval will increase to q4 weeks (cycle 13+) according to IMWG dose-response criteria of \>= VGPR. Further dosing interval increase to q8weeks (cycles 19+) will be done among participants based on response criteria IMWG of \>= CR.

**Intervention Names:**

- Drug: Elranatamab injection

**Label:** Elranatamab injection

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Elranatamab injection

**Description:** Elranatamab (Elrexfio) is a humanized bispecific antibody that targets both BCMA-expressing multiple myeloma (MM) cells and CD3-expressing T cells.

**Name:** Elranatamab injection

**Other Names:**

- Elrexio

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Description:** BCMA levels in blood and their relationship to clinical response and progression.

**Measure:** Exploratory outcome BCMA expression (biologic tumor characteristics)

**Time Frame:** 36 months

**Description:** Feasibility, adherence and satisfaction of remote patient monitoring during the first 9 days of treatment using an outpatient remote monitoring device

**Measure:** Feasibility, adherence and satisfaction of remote patient monitoring

**Time Frame:** First 9 days of treatment.

**Description:** 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.

**Measure:** Patient satisfaction with the use of the remote monitoring device

**Time Frame:** First 9 days of treatment.

#### Primary Outcomes

**Description:** 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.

**Measure:** Hospitalization rate

**Time Frame:** 2 weeks

**Description:** 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.

**Measure:** Rate of grade 3+ infections

**Time Frame:** 24 months

#### Secondary Outcomes

**Description:** Overall response rate, defined by the IMWG criteria.

**Measure:** Overall response rate.

**Time Frame:** 36 months

**Description:** 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.

**Measure:** Progression free survival.

**Time Frame:** 36 months

**Description:** 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.

**Measure:** Duration of response.

**Time Frame:** 36 months

**Description:** 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.

**Measure:** Time to response.

**Time Frame:** 36 months

**Description:** 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).

**Measure:** Adverse Events

**Time Frame:** 36 months

**Description:** 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.

**Measure:** Clinical laboratory data

**Time Frame:** 36 months.

**Description:** OS, defined from the date of study registration to the date or death due to any cause.

**Measure:** Overall survival

**Time Frame:** 36 months

**Description:** Frailty will be measured using the IMWG frailty score and the time for the 4-meter walk test will be recorded.

**Measure:** Patient Frailty

**Time Frame:** To the time of disease progression.

**Description:** Frequency and timing hospitalization will be recorded during the first two weeks of the study treatment.

**Measure:** Frequency and Timing of Hospitalization

**Time Frame:** 2 weeks.

**Description:** QoL during treatment measured using the EORTC QOL Questionnaire-C30 instrument EORTC QLQ-C30

**Measure:** Patient Quality of Life

**Time Frame:** To the time of disease progression.

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** aguirre@mcmaster.ca

**Name:** Emilio Aguirre, CRA,HIT,CHIM

**Phone:** 905-527-2299

**Phone Ext:** 42650

**Role:** CONTACT

**Contact 2:**

**Email:** nasons@mcmaster.ca

**Name:** Sharon Nason

**Phone:** 905-527-2299

**Phone Ext:** 42622

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Calgary

**Contacts:**

***Contact 1:***

- **Email:** nbahlis@ucalgary.ca

- **Name:** Nazir Jacques Bahlis, MD

- **Phone:** 403-944-1880

- **Role:** CONTACT

**Country:** Canada

**Facility:** Arnie Charbonneau Cancer Institute

**State:** Alberta

**Zip:** T2N 4Z6

**Location 2:**

**City:** Edmonton

**Contacts:**

***Contact 1:***

- **Email:** irwindee@ualberta.ca

- **Name:** Irwindeep Sandhu, MD

- **Phone:** 780-432-8757

- **Role:** CONTACT

**Country:** Canada

**Facility:** Cross Cancer Institute

**State:** Alberta

**Zip:** T6G 1Z2

**Location 3:**

**City:** Vancouver

**Contacts:**

***Contact 1:***

- **Name:** Christopher Venner, MD

- **Phone:** 604-877-6000

- **Role:** CONTACT

**Country:** Canada

**Facility:** Vancouver Cancer Center

**State:** British Columbia

**Zip:** V5Z 1L3

**Location 4:**

**City:** Hamilton

**Contacts:**

***Contact 1:***

- **Email:** hira.mian@medportal.ca

- **Name:** Hira Mian, MD

- **Phone:** 905-387-9495

- **Role:** CONTACT

**Country:** Canada

**Facility:** Juravinski Cancer Center

**State:** Ontario

**Zip:** L8V 1C3

**Location 5:**

**City:** Ottawa

**Contacts:**

***Contact 1:***

- **Name:** Arleigh Robertson McCurdy, MD

- **Phone:** 613-737-8899

- **Phone Ext:** 71281

- **Role:** CONTACT

**Country:** Canada

**Facility:** Ottawa Hospital

**State:** Ontario

**Zip:** K1H 8L6

#### Overall Officials

**Official 1:**

**Affiliation:** McMaster University

**Name:** Hira Mian, MD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** OCOG - McMaster University

**Name:** Jim Wright, MD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000020141

- Term: Hemostatic Disorders

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000010265

- Term: Paraproteinemias

- ID: D000001796

- Term: Blood Protein Disorders

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000006474

- Term: Hemorrhagic Disorders

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC25

- Name: Substance Related Disorders

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M12058

- Name: Multiple Myeloma

- Relevance: HIGH

- As Found: Multiple Myeloma

- ID: M27588

- Name: Neoplasms, Plasma Cell

- Relevance: HIGH

- As Found: Multiple Myeloma

- ID: M2157

- Name: Cytokine Release Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M22080

- Name: Neurotoxicity Syndromes

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M21977

- Name: Hemostatic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5059

- Name: Blood Coagulation Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M13178

- Name: Paraproteinemias

- Relevance: LOW

- As Found: Unknown

- ID: M5077

- Name: Blood Protein Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9560

- Name: Hemorrhagic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3947

- Name: Multiple Myeloma

- Relevance: HIGH

- As Found: Multiple Myeloma

- ID: T4120

- Name: Neurotoxicity Syndromes

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000009101

- Term: Multiple Myeloma

- ID: D000054219

- Term: Neoplasms, Plasma Cell

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M4225

- Name: Antibodies

- Relevance: LOW

- As Found: Unknown

- ID: M20194

- Name: Antibodies, Bispecific

- Relevance: LOW

- As Found: Unknown

- ID: M10184

- Name: Immunoglobulins

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
