Nemtabrutinib, Bortezomib, and Rituximab for WM

NCT07464210 | Not Yet Recruiting Phase 2

• 1 other identifier: NEBULA
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II (2 parts), open-label, single arm, multicenter study to evaluate the efficacy and safety of nemtabrutinib in combination with bortezomib and rituximab

Conditions

Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Major response rate (MRR)

  Composite of complete response (CR) + very good partial response (VGPR) + partial response (PR) according to International Workshop on WM (IWWM)-11 response criteria

  At the end of Cycle 6 (each cycle is 28 days)

Secondary Outcomes (5)

• Progression-free survival (PFS)

  through study completion, an average of 2 years

• Overall survival

  through study completion, an average of 2 years

• Overall response rate (ORR)

  At the end of Cycle 24 (each cycle is 28 days)

• complete response (CR) rate

  At the end of Cycle 6 and Cycle 24 (each cycle is 28 days)

• Time to response (TTR)

  through study completion, an average of 2 years

Study Arms (1)

Treatment (NEBULA: Nemtabrutinib + Bortezomib + Rituximab) arm

EXPERIMENTAL

Nemtabrutinib + Bortezomib + Rituximab

Drug: NEBULA

Interventions

NEBULA DRUG

Nemtabrutinib + Bortezomib + Rituximab

Treatment (NEBULA: Nemtabrutinib + Bortezomib + Rituximab) arm

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Confirmed diagnosis of WM in accordance with the consensus panel of the IWWM (per local evaluation), and treatment naïve
• Symptomatic disease meeting at least 1 of the recommendations from the IWWM for requiring treatment.
• Measurable disease defined as serum monoclonal IgM \> 0.5g/dL.
• Is an individual of any sex/gender, who are at least 19 years of age on the day of signing informed consent (ICF).
• Participants Assigned Male Sex at Birth
• If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
• Nemtabrutinib: 12 days
• Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
• Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
• Uses a penile/external condom plus nonparticipant of childbearing potential who is not currently pregnant and should also be advised of the benefit for that partner to use an additional method of contraception, as a condom may break or leak.
• Note: Participants capable of producing ejaculate whose partner is pregnant or breastfeeding must agree to use penile/external condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate.
• \-- Contraceptive use by participants capable of producing sperm should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
• Participants Assigned Female Sex at Birth
• A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:

You may not qualify if:

• The participant must be excluded from the study if the participant meets any of the following criteria:
• Active HBV/HCV infection.
• Positive for human immunodeficiency virus (HIV).
• Gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy).
• Active infection requiring systemic therapy, including IV antibiotics during screening. Participants may be rescreened followed completion of IV antibiotic course.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• QTc prolongation (defined as a QTcF \>450 msecs) or other significant ECG abnormalities including second degree AV block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min).
• A history of anaphylaxis or hypersensitivity to investigational products or components of investigational products (nemtabrutinib, bortezomib, rituximab).
• History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding.
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
• NOTE: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder.
• A POCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Prior use of any BTKi.
• Prior exposure to proteasome inhibitors (bortezomib, ixazomib, carfilzomib).
• Prior exposure to anti-CD20 antibody.

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, 03080, South Korea

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

Sra protein, Drosophila

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

Central Study Contacts

Ja Min Byun, MD, PhD

CONTACT

82-02-2072-7215; jaminbyun@snu.ac.kr

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: Professor, MD, PhD

Study Record Dates

• First Submitted: March 2, 2026
• First Posted: March 11, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2030
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

KR (1)