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

NCT07548450 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCI198712
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (2)

• 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.

  5 years

• 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.

  5 years

Secondary Outcomes (5)

• 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).

  5 years

• 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.

  5 years

• 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.

  5 years

• 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.

  5 years

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

  5 years

Study Arms (2)

Dosing Strategy 1-Mosunetuzumab and Pirtobrutinib

EXPERIMENTAL

Participants 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.

Drug: Pirtobrutinib; Drug: Mosunetuzumab

Dosing Strategy 2- Mosunetuzumab and Pirtobrutinib

EXPERIMENTAL

Participants 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.

Drug: Pirtobrutinib; Drug: Mosunetuzumab

Interventions

Pirtobrutinib DRUG

200 mg daily

Dosing Strategy 1-Mosunetuzumab and Pirtobrutinib; Dosing Strategy 2- Mosunetuzumab and Pirtobrutinib

Mosunetuzumab DRUG

Administered subcutaneously on day one of applicable cycles.

Dosing Strategy 1-Mosunetuzumab and Pirtobrutinib; Dosing Strategy 2- Mosunetuzumab and Pirtobrutinib

Eligibility Criteria

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

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:

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

Sponsors & Collaborators

• University of Utah: lead
• Genentech, Inc.: collaborator
• Eli Lilly and Company: collaborator

Study Sites (1)

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

pirtobrutinib

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

Study Officials

• Narendranath R. Epperla, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Samuel

CONTACT

8015874713; david.samuel@hci.utah.edu

Narendranath Epperla, MD

CONTACT

8015850255; naren.epperla@hci.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2026
• First Posted: April 23, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2034
• Study Completion (Estimated): June 1, 2035
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (1)