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Waldenstrom MacroglobulinemiaPhase 2MPOWERNCT07548450

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

A Phase 2 study testing Pirtobrutinib and Mosunetuzumab in people with Waldenstrom Macroglobulinemia, run by University of Utah at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Waldenstrom Macroglobulinemia
What is being tested?
Pirtobrutinib and Mosunetuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
Nov 2026to Nov 2035
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • Subjects must have an indication for treatment per IWWM
  • 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 (or having undergone surgical sterilization (bilateral oophorectomy of hysterectomy). The following age-specific requirements apply:
  • < 50 years of age:
  • Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
  • Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
  • --≥ 50 years of age:
  • Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
  • Had radiation-induced menopause with last menses >1 year ago; or
  • Had chemotherapy-induced menopause with last menses >1 year ago
  • Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
  • Participants of childbearing potential and participants with a sexual partner of childbearing potential must agree to use a highly effective method of contraception and lactation requirements as described in Sections 5.4.1 and 5.4.2.
  • Able to swallow oral tablets.
  • Clinically significant adverse effects from any prior oncologic treatment (e.g. prior surgery, radiotherapy, or other antineoplastic therapy) must have recovered to grade 1 or have been determined to be clinically stable per the Investigator.
  • Subject or their legal representative is able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Who cannot join

  • 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
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  • 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
  • Major surgery 4 weeks prior to starting study therapy or participant has not fully recovered from major surgery.
  • The diagnosis of another malignancy which, in the opinion of the Investigator, is likely to negatively impact the participant's safety or ability to participate in the study.
  • Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders:
  • Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
  • Unstable angina or acute coronary syndrome within 6 months prior to first dose of study therapy.
  • History of myocardial infarction within 6 months prior to first dose of study therapy
  • QTc prolongation defined as a QTcF > 470 ms.
  • Correction of suspected drug induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation.
  • Correction for underlying bundle branch block (BBB) allowed.
  • Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker
  • ---Left ventricular ejection fraction < 40% within 12 months prior to first dose of study therapy.
  • Any other condition that would, in the Investigator's judgment, contraindicate the participant's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, social/ psychological issues, etc.)
  • Evidence of other clinically significant uncontrolled condition(s) or other clinically significant active disease process which, in the opinion of the investigator, is likely to pose a risk for patient participation.
  • Known HIV infection.
  • Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
  • --Note: Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Participants with positive anti-HBc and negative HBV DNA should be on prophylactic nucleo(t)side analogue therapy to prevent reactivation with serial HBV DNA PCR monitoring Participants positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Known active cytomegalovirus (CMV) infection.
  • History of autoimmune disease, including, but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
  • Patients with a remote history of, or well-controlled, autoimmune disease with a treatment-free interval from immunosuppressive therapy for 12 months may be eligible to enroll if judged to be safe by the investigator.
  • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone are eligible.
  • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
  • Patients with a history of disease-related immune thrombocytopenic purpura, or autoimmune hemolytic anemia may be eligible.
  • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
  • Rash must cover 10% of body surface area
  • Disease is well controlled at baseline and requires only low-potency topical corticosteroids
  • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency oral corticosteroids within the previous 12 months.
  • Positive SARS-CoV-2 test within 7 days prior to enrollment
  • Substance abuse within 12 months prior to screening
  • Medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol or complete the study.
  • Known prior severe hypersensitivity to investigational product or any component in its formulations (CTCAE v 6.0 Grade ≥ 3).
  • Participants taking prohibited medications as described in Section 7.5.10.
  • Subject has received prior standard or investigational anti cancer therapy as specified below:
  • Chimeric antigen receptor T-cell therapy within 60 days prior to Day 1 of Cycle 1.
  • Radioimmunoconjugate within 12 weeks prior to Day 1 of Cycle 1.
  • Prior treatment with monoclonal antibodies, chemotherapy, or antibody-drug conjugates within 4 weeks before first mosunetuzumab administration.
  • Treatment with any anticancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first dose of study treatment.
  • Radiotherapy
  • 14 days for local site radiation therapy
  • 6 weeks for prior radioisotope therapy
  • 12 weeks for 50% pelvic or total body irradiation

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

David Samuel contact

8015874713

david.samuel@hci.utah.edu

Narendranath Epperla, MD contact

8015850255

naren.epperla@hci.utah.edu

United States1 site

  • Huntsman Cancer Institute at University of Utah

    Salt Lake City, Utah, 84112

    David Samuel, 801-587-4713, david.samuel@hci.utah.edu

Other trials in United States

About this study

Official title: A Phase II Study of Mosunetuzumab in Combination With Pirtobrutinib in Patients With Relapsed or Refractory Waldenstrom Macroglobulinemia (MPOWER)

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.

Being tested
Pirtobrutinib, Mosunetuzumab
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PirtobrutinibDrug

    200 mg daily

  • MosunetuzumabDrug

    Administered subcutaneously on day one of applicable cycles.

Study groups in NCT07548450
Study groupRoleWhat they receive
Dosing Strategy 1-Mosunetuzumab and PirtobrutinibExperimentalParticipants receive pirtobrutinib daily on days 1-21 of 21 day cycles. Mosunetuzumab will be administered subcutaneously starting on cycle 2, day 1. If patients have a complete response to treatment, after 9 cycles, they will continue with on pirtobrutinib for a total of 18 cycles. If patients receive a very good partial or minor response, they will continue to receive Mosunetuzumab and Pirtobrutinib for a total of 18 cycles.
Receives: Drug: Pirtobrutinib; Drug: Mosunetuzumab
Dosing Strategy 2- Mosunetuzumab and PirtobrutinibExperimentalParticipants receive pirtobrutinib daily on days 1-21 of 21 day cycles. Mosunetuzumab will be administered subcutaneously starting on cycle 3, day 1. If patients have a complete response to treatment, after 9 cycles, they will continue with on pirtobrutinib for a total of 19 cycles. If patients receive a very good partial or minor response, they will continue to receive Mosunetuzumab and Pirtobrutinib for a total of 19 cycles.
Receives: Drug: Pirtobrutinib; Drug: Mosunetuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The recommended phase 2 dose (RP2D) which will be determined based on the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period.

    To determine the safety and tolerability of mosunetuzumab in combination with pirtobrutinib.

    Measured: 5 years

  2. Best very good partial response (VGPR) or better per the modified IWWM6 criteria.1

    To determine the efficacy of the combination of mosunetuzumab and pirtobrutinib.

    Measured: 5 years

Secondary outcomes (5)

  1. Best response rates including partial response (PR), Best very good partial response (VGPR), complete response (CR), major response (PR+VGPR+CR) and overall response (minor response + major response).

    To evaluate the best response rates of mosunetuzumab + pirtobrutinib.

    Measured: 5 years

  2. Best very good partial response (VGPR)/partial response (PR)/minor response conversion rates from Cycle 8 to 18 (dosing strategy 1(DS1)), and Cycle 9 to 19 (dosing strategy 2(DS2)), as applicable.

    To evaluate the conversion rate from Cycle 8 to 18 (DS1) and Cycle 9 to 19 (DS2), as applicable.

    Measured: 5 years

  3. Duration of response (DoR), defined as the interval of time from the date of initial documented response (minor response or better per modified IWWM6 criteria) to the time of relapse or death from any cause.

    To evaluate the DoRof the study population.

    Measured: 5 years

  4. Progression free survival (PFS) as defined as the time from study therapy initiation to the time documented disease progression (as assessed by modified IWWM6 criteria) or death from any cause.

    To assess median and 2-year PFS.

    Measured: 5 years

  5. Overall survival (OS) as defined as the time from study therapy initiation until death from any cause.

    To assess median and 2-year OS in this study population.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Apr 2026
  2. Study startNov 2026 (estimated)
  3. Primary completionNov 2034 (estimated)
  4. Study completionNov 2035 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07548450
Sponsor's protocol ID
HCI198712
Acronym
MPOWER
Status last verified
Apr 2026
First submitted
16 Apr 2026
Last updated
24 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pirtobrutinib and Mosunetuzumab in people with Waldenstrom Macroglobulinemia, run by University of Utah at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 66 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact David Samuel (8015874713, david.samuel@hci.utah.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The recommended phase 2 dose (RP2D) which will be determined based on the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period. (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07548450.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.

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