ABBV-383 for the Treatment of Relapsed Refractory Waldenström Macroglobulinemia

NCT07420959 | Not Yet Recruiting Phase 1 FDA Drug

• 3 other identifiers: MC230817NCI-2026-0043425-007511
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of ABBV-383 and to see how well it works in treating patients with Waldenström macroglobulinemia that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). ABBV-383 is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens).

Conditions

Recurrent Waldenstrom Macroglobulinemia; Refractory Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of etentamig (ABBV-383) (Phase 1)

  MTD is defined as the highest tested dose level that is determined to have acceptable toxicity and tolerability based on dose-limiting toxicity (DLT) definitions. An unacceptable dose level is one that induces DLT in at least one-third of patients (at least 2 of a maximum of 6 new patients). The MTD of ABBV-383 thus will be the highest tested dose level where at most one out of 6 patients treated have a reported DLT.

  Up to 1 cycle (Cycle length = 28 days)

• Very good partial response (VGPR) or better response as the best response achieved (Phase 2)

  The International Workshop on Waldenström's Macroglobulinemia-11 (IWWM-11) Response Criteria will be used for response assessment. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. 95% confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

  Within 12 cycles of initiation of therapy (Cycle length = 28 days)

Secondary Outcomes (7)

• Major response rate (MRR)

  At 6 and 12 months

• Progression-free survival (PFS)

  6 and 12 months

• Time to response

  Up to 2 years

• Duration of response

  Up to 2 years

• Time to next treatment

  Up to 2 years

Study Arms (1)

Treatment (ABBV-383)

EXPERIMENTAL

Patients receive ABBV-383 IV as a single push or over 30 minutes to 4 hours on days 1 and 4 of cycle 1 and on day 1 of subsequent cycles. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or PET/CT during screening and blood and urine sample collection and bone marrow aspiration and biopsy throughout the trial. Additionally, patients with extramedullary disease undergo CT or PET/CT throughout the trial.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Biological: Etentamig; Procedure: Positron Emission Tomography; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (ABBV-383)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Treatment (ABBV-383)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (ABBV-383)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (ABBV-383)

Etentamig BIOLOGICAL

Given IV

Also known as: ABBV 383, ABBV-383, ABBV383, Anti-alpha BCMA/Anti-alpha CD3 T-cell Engaging Bispecific Antibody TNB-383B, Anti-BCMA x aCD3 T-BsAb TNB-383B, Anti-BCMA x aCD3 T-cell Engaging Bispecific Antibody TNB-383B, Anti-BCMA/Anti-CD3 T-cell Engaging Bispecific Antibody ABBV-383, BCMA x CD3 T-cell Engaging Bispecific Antibody ABBV-383, TNB 383B, TNB-383B, TNB383B

Treatment (ABBV-383)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (ABBV-383)

Questionnaire Administration OTHER

Ancillary studies

Treatment (ABBV-383)

Eligibility Criteria

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

You may qualify if:

• PRE-REGISTRATION: Age ≥ 18 years
• PRE-REGISTRATION: Histological confirmation of relapsed and/or refractory Waldenstrom macroglobulinemia, with known prior exposure to a Bruton tyrosine kinase (BTK) inhibitor unless medically contraindicated. Note: although not preferred, archival bone marrow tumor tissue that was collected within 12 weeks prior to screening and without intervening anti- BCMA treatment may be used if the patient is unwilling to provide a fresh pretreatment marrow biopsy
• PRE-REGISTRATION: Measurable disease as defined as serum immunoglobulin M (IgM) levels ≥ 0.5 g/dL (500 mg/dL)
• PRE-REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• PRE-REGISTRATION: Subject is naïve to treatment with ABBV-383 or anti-BCMA bispecific antibodies
• PRE-REGISTRATION: Hemoglobin ≥ 8.0 g/dL (obtained ≤ 14 days prior to pre-registration)
• PRE-REGISTRATION: Absolute neutrophil count (ANC) ≥ 1000/mm\^3 \[neutropenia due to marrow infiltration may be supported by granulocyte colony-stimulating factor (GCSF)\] (obtained ≤ 14 days prior to pre-registration). Transfusion and/or growth factor support is permitted prior to assessment, but neutrophils, platelets, and hemoglobin must be stable for ≥ 72 hours after transfusion and/or growth factor administration for the subject to be eligible
• PRE-REGISTRATION: Platelet count ≥ 75,000/mm\^3 (obtained ≤ 14 days prior to pre-registration) EXCEPTION: If thrombocytopenia deemed to be related to the bone marrow infiltration (disease burden) by WM cells, platelet count threshold of ≥ 50,000 is acceptable. Transfusion and/or growth factor support is permitted prior to assessment, but neutrophils, platelets, and hemoglobin must be stable for ≥ 72 hours after transfusion and/or growth factor administration for the subject to be eligible
• PRE-REGISTRATION: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 14 days prior to pre-registration) (except for subjects with documented Gilbert's syndrome, in which case direct bilirubin must be ≤ 2 x ULN)
• PRE-REGISTRATION: Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (obtained ≤ 14 days prior to pre-registration)
• PRE-REGISTRATION: Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (obtained ≤ 14 days prior to pre-registration)
• PRE-REGISTRATION: Calculated creatinine clearance ≥ 30 ml/min using the Cockcroft-Gault formula (obtained ≤ 14 days prior to pre-registration)
• PRE-REGISTRATION: Negative pregnancy test done ≤ 7 days prior to pre-registration, for persons of childbearing potential only. Note: Subjects must have 2 negative results for pregnancy tests prior to initiating therapy. The first test (serum) should be performed during the screening period prior to first dose of study drug and the second test (urine, minimum sensitivity of 25 IU/L). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• PRE-REGISTRATION: Willing to follow strict birth control measures as suggested by the study
• PRE-REGISTRATION: Female participants: Female participant is eligible to participate if she is not pregnant or breast feeding, and at least one of the following conditions applies:

You may not qualify if:

• PRE-REGISTRATION: Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential (and persons able to father a child) who are unwilling to employ adequate contraception
• PRE-REGISTRATION: Subject has known allergic reaction, significant sensitivity, or intolerance to constituents of the study drugs (and excipients) and/or other products in the same class
• PRE-REGISTRATION: Any of the following prior therapies:
• Major surgery ≤ 4 weeks prior to registration
• Chemotherapy ≤ 2 weeks prior to registration
• An investigational therapy, including chemotherapy, radiotherapy, biological, immunotherapy or targeted small molecule agents within 5 half-lives (or 2 weeks, if half-life is unknown) prior to registration
• Patient has received steroid therapy given with anti-neoplastic intent ≤ 7 days prior registration
• Autologous stem cell transplant ≤ 12 weeks or allogeneic transplant ≤ 24 weeks prior to registration
• Organ transplant requiring continued use of immunosuppressants
• Live, attenuated vaccines ≤ 4 weeks prior to registration
• Received a monoclonal antibody given with anti-neoplastic intent ≤ 30 days prior to registration
• PRE-REGISTRATION: Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

Specimen Handling; Biopsy; Magnetic Resonance Spectroscopy

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; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Prashant Kapoor, MD

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Cancer Center Clinical Trials Study Coordinator

CONTACT

507-293-6386

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2026
• First Posted: February 19, 2026
• Study Start: March 25, 2026
• Primary Completion (Estimated): March 25, 2036
• Study Completion (Estimated): March 25, 2038
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

US (1)