Mosunetuzumab in Combination With Pirtobrutinib in Patients With Relapsed or Refractory Waldenstrom Macroglobulinemia (MPOWER)

Starting soon · Phase 2

Conditions studied: Waldenstrom Macroglobulinemia

In brief

The purpose of this clinical trial it to test the safety and tolerability of the study drugs mosunetuzumab in combination with pirtobrutinib in patients with relapsed or refractory Waldenstrom's Macroglobulinemia.

Key facts

Study ID: NCT07548450
Run by: University of Utah
People needed: 25
Starts: 2026-06-01
Expected to finish: 2035-06-01
Last updated by the study team: 2026-04-23

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Subjects aged ≥ 18 years with documented diagnosis of WM with the definition of measurable disease
Subjects who are able to comply with the study protocol.
Subjects with relapsed or refractory WM who have received at least one prior line of therapy.
Must have received prior treatment with covalent BTK inhibitor or have declined such treatment.
Prior autologous stem cell transplant is permitted if completed ≥ 100 days prior to treatment.
Prior allogeneic transplants are not permitted.
Subjects must have an indication for treatment per 2nd International Workshop on WM35
ECOG Performance Status ≤ 2
Adequate organ function as defined as:
Hematologic:
Absolute neutrophil count ≥ 1000/mm3 independent of G-CSF support, unless there is documented bone marrow involvement or splenomegaly with ensuing cytopenia in which case ANC of 750 cells/mm3 (0.75 x 10\^9/L) is permissible. Also, there should be no evidence of myelodysplasia or hypoplastic bone marrow.
Platelet count ≥75,000 cells/mm3 (≥75 x 10\^9/L) independent of transfusion support unless there is documented bone marrow involvement in which case platelet count of 50,000 cells/mm3 (50 x 10\^9/L) is permissible. Patients must be responsive to transfusion support if given for thrombocytopenia and patients refractory to transfusion support are not eligible. Also, there should be no evidence of myelodysplasia or hypoplastic bone marrow.
Hemoglobin of ≥ 8.5 g/dL (≥ 85 g/L) independent of transfusion support unless there is documented bone marrow involvement or splenomegaly with ensuing cytopenia in which case hemoglobin of 7 g/dL (70 g/L) is permissible. Patients must be responsive to transfusion support if given for anemia and patients refractory to transfusion support are not eligible. Also, there should be no evidence of myelodysplasia or hypoplastic bone marrow.
Coagulation: Activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin (PT) or (international normalized ratio (INR) not greater than 1.5 x ULN.
Hepatic:
Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN) or ≤3 x ULN with document liver involvement and/ or Gilbert's disease
AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
Participants with liver metastases will be allowed to enroll with AST and ALT levels ≤ 5 x ULN.
Renal:
Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula.
Participants must adhere to the following sex and contraceptive/barrier requirements:
If participant is of childbearing potential, they must have a negative pregnancy test
For participants of non-childbearing potential: The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
< 50 years of age:
Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and

You may not qualify if…

History of transformation of indolent disease to DLBCL
Active or history of CNS lymphoma or leptomeningeal infiltration
Prior treatment with a non-covalent BTK inhibitor
Prior treatment with CD20-directed bispecific antibody therapy
Receiving other investigational agents.
Receipt of a live, attenuated vaccine within 4 weeks before first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study
Patients must not receive live, attenuated vaccines (e.g., FluMistâ) while receiving study treatment or after the last dose until B-cell recovery to the normal ranges.
Inactivated influenza vaccination should be given during the influenza season only.
An approved coronavirus disease 2019 (COVID-19) vaccine (messenger RNA [mRNA], inactivated virus, and replication deficient viral vector vaccines) is allowed, as these are not considered live vaccines.
Receipt of systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) with the exception of corticosteroid treatment £ 10 mg/day prednisone or equivalent within 2 weeks prior to the first dose of mosunetuzumab
Patients who received acute, low-dose, systemic immunosuppressant medications (e.g., single dose of dexamethasone for nausea or B-symptoms) may be enrolled in the study if deemed appropriate by the investigator.
The use of inhaled corticosteroids is permitted.
The use of mineralocorticoids for management of orthostatic hypotension is permitted.
The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted.
History of solid organ transplantation
History of severe allergic or anaphylactic reaction to humanized, chimeric or murine monoclonal antibodies (MAbs) or known sensitivity or allergy to murine products
Known active bacterial, viral (including SARS-CoV-2), fungal, or other infection, or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1
Known or suspected chronic active Epstein-Barr virus (EBV) infection
Known or suspected history of macrophage activation syndrome (MAS) / hemophagocytic lymphohistiocytosis (HLH)
History of confirmed progressive multifocal leukoencephalopathy (PML)
Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
Patients with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 1 year and have no significant residual neurologic deficits as judged by the investigator are allowed.
Patients with a history of epilepsy who have had no seizures in the past 1 year while not receiving any anti-epileptic medications are allowed.
Clinically significant active malabsorption syndrome or other conditions likely to affect gastrointestinal absorption of the study drug
History of bleeding diathesis

Where it is running

Huntsman Cancer Institute at University of Utah — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

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