Linvoseltamab in Addition to Lenalidomide (L2) During Maintenance Therapy of NDMM to Deepen Responses or Redrive MRD Negativity After Relapse

NCT06910124 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20241138
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether giving linvoseltamab with lenalidomide during maintenance treatment to participants with multiple myeloma will:

1. 1.Get rid of any residual multiple myeloma cells in participants' bodies which is known as minimal residual disease negative (MRD-) status. For participants that start the study with residual multiple myeloma cells in participants' bodies: to determine how long you remain MRD-.
2. 2.Increase the length of time that participants' disease is controlled. For participants with relapsed disease, to determine whether participants can re-attain MRD- status.
3. 3.Increase the length of time that participants' disease responds to treatment.

Conditions

Multiple Myeloma

Keywords

Newly Diagnosed Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Minimum Residual Disease Negative Conversion Rate

  The number of patients who experience MRD negativity (10\^-5 sensitivity by 12 cycles of linvoseltamab (MRD conversion rate) will be determined by dividing this number of MRD negative responses by the total number of evaluable patients. MRD negativity rate (\<10\^-5) by 12 cycles of linvoseltamab

  12 months

Secondary Outcomes (8)

• Minimum Residual Disease Negative Conversion Rate

  6 months

• Sustained MRD Negativity Rate

  Up to 2 years

• Overall Response Rate

  Up to 12 months

• Best Overall Response (BOR)

  Up to 12 months

• Duration of Response (DOR)

  Up to 4.5 years

Study Arms (2)

Cohort 1 - Linvoseltamab Treatment Group

EXPERIMENTAL

Participants in this group are currently receiving lenalidomide maintenance therapy for ≤12 months will have linvoseltamab added to the lenalidomide maintenance therapy and receive treatment with the combination for up to 24 cycles. Total participation duration is up to 4.5 years

Biological: Linvoseltamab; Drug: Lenalidomide

Cohort 2 - Lenalidomide Treatment Group

EXPERIMENTAL

Participants in this group are currently receiving lenalidomide maintenance therapy but have relapsed disease within 12 months of starting maintenance will have Linvoseltamab added to lenalidomide maintenance and receive treatment with the combination for up to 24 cycles. Total participation duration is up to 4.5 years

Biological: Linvoseltamab; Drug: Lenalidomide

Interventions

Linvoseltamab BIOLOGICAL

Participants will receive Linvoseltamab intravenously (IV) according to the following schedule and regimen, for up to 24 cycles, each cycle lasting 28 days: * Cycle 1 Day 1: 5mg * Cycle 1 Day 8: 25mg * Cycle 1 Days 15, 22: 100mg * Cycles 2 and 3, Days 1, 8, 15, 22: 100mg * Cycles 3 and 6, Days 1 and 15: 100mg * Cycles 7 through 24: 100mg

Cohort 1 - Linvoseltamab Treatment Group; Cohort 2 - Lenalidomide Treatment Group

Lenalidomide DRUG

Participants will take 10mg of Lenalidomide maintenance therapy standard of care by mouth daily from days 1 through 21 of each 28 day cycle of Linvoseltamab therapy. Lenalidomide therapy will begin on Cycle 2 Day 1 of Linvoseltamab therapy.

Cohort 1 - Linvoseltamab Treatment Group; Cohort 2 - Lenalidomide Treatment Group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of newly-diagnosed multiple myeloma (NDMM) per International Myeloma Working Group (IMWG) documented initially prior to any treatment (Kumar et al., 2016).
• Documentation of having received a triplet or quadruplet based initial combination therapy containing at least two of the following: Immunomodulatory drug (IMiD), proteosome inhibitor (PI), and/or anti-cluster of differentiation 38 (anti-CD38).
• Documentation of receiving induction therapy with or without high-dose melphalan with autologous stem cell transplant (HDM-ASCT) and receiving lenalidomide maintenance therapy ≤ 12 months.
• Cohort 1: at the time of assessment, the patient's current response is a partial response (PR), very good partial response (VGPR), or complete response (CR) but MRD+ by the FDA-cleared next-generation sequencing (NGS) Adaptive clonoseq assay.
• Cohort 2: at the time of assessment, the patient has a relapse from their initial complete response (CR) (\<CR response are ineligible) post induction but do not meet criteria for IMWG progression (eg, patients who no longer meet criteria for CR but whose M-protein is ≤ 0.5 g/dL and/or immunofixation has turned positive, and/or have converted to MRD+ by the FDA-cleared NGS Adaptive clonoseq assay).
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 3 (Appendix A)
• Adequate organ function
• Absolute neutrophil count (ANC) ≥ 1000/microlitre (unless patient has ethnic neutropenia)
• Platelets ≥ 50,000/microlitre
• Hemoglobin ≥ 8 g/dL (transfusions permitted)
• Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) or direct bilirubin ≤ ULN for patients with total bilirubin levels \> 1.5 ULN (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 X ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) ≤ 3 X ULN
• Serum creatinine ≤ 1.5 X ULN (except if due to myeloma) or calculated estimated glomerular filtration rate (eGFR)/creatinine clearance (CrCl) (by Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease, or Cockcroft-Gault) ≥ 15 mL/min/1.73 m2
• Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 90 days following the last dose of study treatment.
• Willing and able to provide written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.

You may not qualify if:

• Patients who have received prior systemic therapies for Multiple Myeloma (MM) other than initial IMiD/PI/anti CD38/HDM-ASCT-based combination therapy.
• Treatment with corticosteroids for MM or other indications is permitted.
• Prior radiation therapy and surgery is permitted.
• Patients who are receiving any other investigational agents unless deemed not to interfere with the study by the Principal Investigator (PI).
• Patients who receive a live attenuated vaccine within 4 weeks of scheduled study treatment administration.
• Contraindication to any concomitant medication, including those medications administered for infusion reaction, antiviral, antibacterial, anticoagulation, tumor lysis, or hydration prophylaxis given prior to therapy.
• Patient has any of the following:
• a. Human immunodeficiency virus (HIV)-positive with 1 or more of the following: i. History of acquired immune deficiency syndrome (AIDS)-defining conditions Cluster of differentiation 4 count \< 350 cells/mm3 ii. Detectable viral load during screening or within 6 months prior to screening iii. Not receiving highly active anti-retroviral therapy iv. Had a change in antiretroviral therapy within 6 months of the start of screening v. Receiving antiretroviral therapy that may interfere with study treatment as assessed after discussion with the PI
• b. Hepatitis B infection (ie, hepatitis B surface antigen (HBsAg) or hepatitis B virus (HBV) DNA positive). Patients with resolved infection (ie, patients who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-Hepatitis-C\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of HBV deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status. Exception: Patients with serologic findings suggestive of HBV vaccination (anti HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination do not need to be tested for HBV DNA by PCR.
• c. Active hepatitis C (HCV) infection as measured by positive HCV-ribonucleic acid (RNA) testing. Participants with a history of HCV antibody positivity must undergo HCV-RNA testing. If a participant with history of chronic hepatitis C infection (defined as both HCV antibody and HCV RNA positive) completed antiviral therapy and has undetectable HCV RNA 12 weeks following the completion of therapy, the participant is eligible for the study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the experimental agents used in study.
• Female patient refuses to discontinue breastfeeding her infant during study treatment or within 3 months after receiving the last dose of study treatment.
• Participant plans to father a child while enrolled in this study or within 3 months after the last dose of study treatment.
• Presence of the following cardiac conditions:
• New York Heart Association stage III or IV congestive heart failure

Sponsors & Collaborators

• Dickran Kazandjian, MD: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide

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

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Dickran Kazandjian, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dickran Kazandjian, MD

CONTACT

305-243-5001; dkazandjian@miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Clinical

Study Record Dates

• First Submitted: March 27, 2025
• First Posted: April 4, 2025
• Study Start: December 2, 2025
• Primary Completion (Estimated): December 2, 2032
• Study Completion (Estimated): December 2, 2032
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)