ELISA in Relapsed/Refractory MM

NCT06832865 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 24-727
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label phase 2 study of elranatamab in combination with isatuximab administered subcutaneously in patients with relapsed and refractory multiple myeloma (RRMM) who have received at least two prior lines of therapy and who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). The subcutaneous injection method of isatuximab administration, including the device used to administer isatuximab, is investigational.

Conditions

Relapsed Refractory Multiple Myeloma (RRMM); Relapsed Refractory Multiple Myeloma

Keywords

Prior lines of therapy; relapsed and refractory multiple myeloma; RRMM

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Objective Response will be classified using the International Myeloma Working Group (IMWG) Uniform Response criteria. The rate (ORR) will be calculated using a Simon's two-stage design to test the null hypothesis that the ORR ≤ 0.40 versus the alternative that ORR ≥ 0.60. All patients who receive at least one complete cycle of treatment will be included in a response evaluation. Participants who do not complete cycle 1 (i.e., due to disease progression or who die prior to the end of cycle 1) will not be considered evaluable for response; these participants may be replaced. In the first stage, 22 patients will be accrued. If there are 10 or fewer responses in these 22 patients, the study will be stopped. Otherwise, study will continue to enroll to a total of 30. The null hypothesis will be rejected if 16 or more responses are observed in 30 patients.

  Day 1 to 2 years post-treatment.

Secondary Outcomes (5)

• Incidence of Drug Related Toxicities

  Day 1 to 30 days post-treatment (30 days post last dose). Participants can receive treatment until disease progression, unacceptable toxicity, or withdrawal.

• Median Progression Free Survival (PFS)

  Day 1 through end of follow-up, up to 5 years.

• Median Overall Survival (OS)

  Day 1 through end of follow-up, up to 5 years.

• Rate of Minimal Residual Disease (MRD) status in participants who have achieved very good partial response (VGPR) or complete response (CR)

  Screening through 24 months on treatment.

• Sustained minimal residual disease (MRD) negative status

  Day 1 through 24 months on treatment.

Study Arms (1)

Elranatamab + Isatuximab-irfc

EXPERIMENTAL

Elranatamab will be administered via subcutaneous (SC) injection usually into the abdomen or lower stomach at the following visits during each 28-day cycle: * Cycle 1: Days 1, 4, 8, 15, 22 * Cycles 2-6: Days 1 and 15 * Cycles 7+: Day 1. Isatuximab for SC administration will be administered via subcutaneous (SC) injection usually into the abdomen or lower stomach, using an investigational injector device called the on-body delivery system at the following visits during each 28-day cycle: * Cycles 2-6: Days 1 and 15 * Cycles 7+: Day 1 This will continue as long as the participant is receiving treatment.

Drug: elranatamab; Drug: Isatuximab SC; Device: Isatuximab SC-OBDS

Interventions

elranatamab DRUG

Subcutaneously injected study drug, usually into the abdomen or lower stomach. Each vial of elranatamab contains a sufficient amount of product to ensure an extractable volume of 1.9 mL at a concentration of 40 mg/mL. The dosing is as follows: * Cycle 1 Day 1: 12 mg/0.3 mL * Cycle 1 Day 4: 32 mg/0.8 mL * Cycle 1 Day 8, 15, 22: 76 mg/1.9 mL * Cycles 2-6, Day 1 and 15: 76 mg/1.9 mL * Cycles 7+, Day 1: 76 mg/1.9 mL

Also known as: PF-06863135

Elranatamab + Isatuximab-irfc

Isatuximab SC DRUG

Isatuximab (SAR650984) is an IgG1 derived monoclonal antibody binding selectively the human CD38 membrane protein. Subcutaneously (SC) injected study drug with each vial containing 140 mg/mL (1400 mg/10mL) isatuximab. Isatuximab SC will be injected using the investigational OBDS and in the following doses: * Cycles 2-6, Day 1 and 15: 1400 mg/10 mL * Cycles 7+ Day 1: 1400 mg/10 mL

Also known as: SAR650984, Isatuximab irfc

Elranatamab + Isatuximab-irfc

Isatuximab SC-OBDS DEVICE

The On Body Delivery System (OBDS) also called Isatuximab SC Wearable Injection System, is a sterile, single-use, disposable, elastomeric, user-filled investigational medical device. The OBDD has a reservoir for the drug product (isatuximab). A self-contained, integrated needle (with manual insertion and automatic retraction mechanism) is provided within the OBDS. The OBDS will be used to inject isatuximab each time the participant receives isatuximab in this study. Study drug administration will be done by trained medical professionals in the clinic. The OBDS device will be prepared by the medical professional, placed on the abdomen using the adhesive (sticky) pads that are on the device, the study drug (isatuximab) will be injected, and then the device will be removed.

Also known as: On Body Delivery System (Device), OBDS, Isatuximab Subcutaneous Injection Device (On Body Delivery System, OBDS), Isatuximab SC Wearable Injection System

Elranatamab + Isatuximab-irfc

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. This study will enroll patients with relapsed and refractory multiple myeloma who have had at least 2 prior lines of therapy including patients who have had previous treatment with both immunomodulatory drugs (IMiDs) and a proteasome inhibitor (PI). Prior therapy with anti-CD38 and anti-B cell maturation antigen (BCMA) target will be permitted except an anti-BCMA T cell engager. Patients cannot be refractory to an anti-CD38 antibody.
• \. Measurable disease of multiple myeloma as defined by at least one of the following:
• a. Serum monoclonal protein ≥ 0.5 g/dL. Patients with IgD disease and lower amounts of monoclonal protein may be permitted to enroll with PI approval
• b. ≥ 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
• c. Serum free light chain ≥ 100 mg/L (10 mg/dL) and abnormal serum free kappa to serum free lambda light chain (FLC) ratio (\<0.26 or \>1.65)
• \. Age ≥18 years.
• a. The effects of elranatamab and isatuximab on the developing human fetus are unknown. For this reason and because anti-BCMA bispecific antibodies are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 months after the last dose of elranatamab and 5 months after the last dose of isatuximab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• \. ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• \. Participants must have adequate organ and marrow function as defined below:
• a. ANC ≥ 1000/μL. G-CSF is not permitted within 7 days of screening.
• b. Platelet count ≥ 50,000/µL. Platelet transfusion is not permitted within 7 days of screening.
• c. Hemoglobin ≥ 8 g/dL. Red blood cell transfusions are permitted to meet eligibility criteria.
• d. Calculated creatinine clearance of ≥ 30 mL/min by Cockcroft-Gault equation.
• e. Patient has adequate hepatic function, as evidenced by each of the following:
• Serum bilirubin values \< 2 mg/dL; and

You may not qualify if:

• \. Patients with active plasma cell leukemia, POEMS syndrome, or amyloidosis are excluded from this trial.
• \. Stem cell transplant within 12 weeks prior to enrollment, or active GVHD.
• \. Ongoing Grade ≥2 peripheral sensory or motor neuropathy.
• \. History of any grade peripheral sensory or motor neuropathy with prior BCMA directed therapy. History of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
• \. Previous treatment with an anti-BCMA bispecific T cell engager.
• a. Prior treatment with anti-BCMA CAR-T and/or ADC therapy is permitted; however, the participant cannot be refractory to this therapy if it was administered as the last line prior to study enrollment.
• \. Participants who are receiving any investigational agents currently.
• \. Participants who have had myeloma therapy or investigational drug within 2 weeks prior to start of treatment or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
• \. Known or suspected hypersensitivity to the study drug or any components of the device (e.g. adhesive which contains acrylic).
• \. Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as any of the following within 6 months prior to enrollment:
• a. Acute myocardial infarction, acute coronary syndromes (e.g., unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, pericardial effusion);
• b. Clinically significant cardiac arrhythmias (e.g., uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
• c. Thromboembolic or cerebrovascular events (e.g., transient ischemic attack, cerebrovascular accident, deep vein thrombosis \[unless associated with a central venous access complication\] or pulmonary embolism);
• \. Participants with known active HBV, HCV, HIV, or any active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 14 days prior to enrollment. Per institutional protocol, HBV DNA testing by PCR is mandatory for subjects at risk for HBV reactivation.
• \. 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 and or other cancers treated with curative intent.

Sponsors & Collaborators

• Pfizer: collaborator
• Sanofi: collaborator
• Massachusetts General Hospital: lead

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

isatuximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Noopur Raje, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Noopur Raje, MD

CONTACT

617-724-1969; nraje@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 13, 2025
• First Posted: February 18, 2025
• Study Start: August 14, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (3)