ABBV-383 for Relapsed or Refractory Waldenström Macroglobulinemia
This study is testing a drug called etentamig (ABBV-383) for people with Waldenström macroglobulinemia that has come back after treatment (relapsed) or isn't responding to treatment (refractory). ABBV-383 is a type of monoclonal antibody, which is a protein designed to target and interfere with cancer cell growth. The study aims to find the safest and most effective dose of ABBV-383 and see how well it works. You may be able to join if you are at least 18 years old and have relapsed or refractory Waldenström macroglobulinemia, especially if you've had a Bruton tyrosine kinase (BTK) inhibitor before. Success in the study would mean finding a safe dose and seeing a good or very good response to the treatment within about a year.
- Study design
- This is a Phase 1/2 interventional study, meaning it looks at both safety and effectiveness. It plans to enroll 38 participants.
- What's involved
- You would undergo blood and urine tests, bone marrow aspirations and biopsies, and CT or PET/CT scans. You would also receive etentamig (ABBV-383) intravenously.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study measures responses within 12 cycles of treatment initiation, with each cycle lasting 28 days.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT07420959
ABBV-383 for the Treatment of Relapsed Refractory Waldenström Macroglobulinemia
Not Yet Recruiting
PHASE1Ages 18+InterventionalTreatmentMayo ClinicInvestigator-initiated
~38 participants
Updated 2026-07-08 on ClinicalTrials.gov
What's tested:Biospecimen CollectionBone Marrow AspirationBone Marrow BiopsyComputed TomographyEtentamigPositron Emission Tomography
At a glance
Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Maximum tolerated dose (MTD) of etentamig (ABBV-383) (Phase 1)
Measured over Up to 1 cycle (Cycle length = 28 days)
+1 more outcome measured
Conditions
NCT07420959
Where you'd take part
This study runs at 1 site. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.
Mayo Clinic in Rochester
Rochester, Minnesotastudy coordinator listed
Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.
Study leadership
- Prashant Kapoor, MD · PRINCIPAL_INVESTIGATOR · Mayo Clinic in Rochester
Who to contact
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Eligibility criteria
Inclusion
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:
Is not a woman of childbearing potential (WOCBP) OR
Due to the risk for embryo-fetal toxicity and prescribed under a pregnancy prevention/controlled distribution program, WOCBP participants will be eligible if they commit to either:
Abstain continuously from heterosexual sexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
To use birth control as follows:
Two methods of reliable birth control (one method that is highly effective and one additional effective (barrier) method), beginning 4 weeks prior to initiating treatment with lenalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of lenalidomide treatment
PRE-REGISTRATION: Male patients: Male participants are eligible to participate if they agree to the following from the time of first dose of study treatment until 28-days after the last dose of lenalidomide, to allow for clearance of any altered sperm:
Refrain from donating sperm PLUS either:
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR
Must agree to use contraception/barrier as detailed below:
Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of \< 1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females)
Note: Subjects of childbearing potential must practice at least one of the specified method of birth control with partner(s) initiated prior to first dose of study drug administration to 90 days after the last dose of study drug. These methods include the following:
A barrier method of contraception (including male and female condoms with or without spermicide) plus one of the following hormonal contraceptives:
Combined (estrogen and progestogen containing) hormonal contraception associated with the inhibition of ovulation
Oral, intravaginal or transdermal
Progestogen-only hormonal contraception associated with the inhibition of ovulation
Oral, injectable, implantable
An intrauterine device (IUD)
Intrauterine hormone-releasing system (IUS)
Bilateral tubal occlusion
Vasectomized partner
Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment, starting the day prior to first dose of study drug, for the duration of the study, and for 90 days after the last dose of study drug). Total sexual abstinence should only be used as a contraceptive method if it is in line with the subjects' usual and preferred lifestyle. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to the investigational medicinal product (IMP), and withdrawal are not acceptable methods of contraception.
PRE-REGISTRATION: Provide written informed consent and is willing to comply with the tests required per the protocol
PRE-REGISTRATION: Willingness to provide mandatory blood and bone marrow samples specimens for correlative research
PRE-REGISTRATION: Rochester only: Willingness to enroll in Institutional Review Board (IRB) #521-93
REGISTRATION: Ability to complete questionnaire(s) by themselves or with assistance
REGISTRATION: Negative pregnancy test done ≤ 7 days prior to 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
REGISTRATION: Subject was pre-registered ≤ 14 days prior to registration
Exclusion
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
PRE-REGISTRATION: Immunocompromised patients and patients with a known history of human immunodeficiency virus (HIV). Subjects with HIV may be permitted provided that the subject has an undetectable HIV viral load by standard clinical assays on antiretroviral medication \[Highly Active Antiretroviral Therapy (HAART)\] and is able to tolerate study treatment per investigator's judgement. Subjects with active, hepatitis C virus or active hepatitis B virus infection \[subjects with resolved infection (hepatitis B virus surface antigen (HbsAg) negative, but hepatitis B virus core antibody (antiHBc) or hepatitis B virus surface antibody (antiHBs) positive\] must be screened using real-time polymerase chain reaction (PCR) of hepatitis B virus (HBV) deoxyribonucleic acid (DNA).
PRE-REGISTRATION: Uncontrolled intercurrent life threatening illness including, but not limited to:
Ongoing or active infection
Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia
Psychiatric illness/social situations that would limit compliance with study requirements
Any organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the metabolism of ABBV 383 or put the study outcomes at undue risk specifically
A subject with history of stroke or intracranial hemorrhage within ≤ 24 weeks prior to registration
Concurrent light and/or heavy chain amyloidosis or central nervous system (CNS) involvement with Waldenström Macroglobulinemia (WM) (Bing Neel syndrome)
PRE-REGISTRATION: Other active malignancy other than WM ≤ 3 years prior to registration EXCEPTIONS: with the exception of a) adequately treated in situ carcinoma of the cervix uteri, b) adequately treated basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, c) prostate cancer Gleason grade 6 or lower AND with stable prostate specific antigen levels off treatment; d) previous malignancy confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study
REGISTRATION: If any of the following exist at screening, subject will not be eligible for trial because this trial involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
Pregnant women
Nursing women
Men or women of childbearing potential who are unwilling to employ adequate contraception (per protocol)
What this trial measures
- Maximum tolerated dose (MTD) of etentamig (ABBV-383) (Phase 1)Up to 1 cycle (Cycle length = 28 days)
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.
- Very good partial response (VGPR) or better response as the best response achieved (Phase 2)Within 12 cycles of initiation of therapy (Cycle length = 28 days)
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.