Phase 2 Study Of Mosunetuzumab In Patients With Chronic Lymphocytic Leukemia With Positive MRD

NCT07566364 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2026-0168NCI-2026-03445
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the therapeutic efficacy of mosunetuzumab, a bispecific antibody targeting CD20 and CD3 in patients who have detectable chronic lymphocytic leukemia (CLL) after receiving Bruton's tyrosine kinase inhibitors (BTKis) for at least 6 months and have no clinical or laboratory evidence of disease progression.

Conditions

Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (2)

Phase 2 Lead-In Phase: Treatment with Mosunetuzumab Inpatient

EXPERIMENTAL

Treatment will be administered inpatient during dose step up dosing during Cycle 1 (days 1, 8, 15) and then on cycles 2 and above mosunetuzma will be administered on day 1. all cycles will be 21 days long.

Drug: Mosunetuzumab

Phase 2: Treatment with Mosunetuzuma Outpatient

EXPERIMENTAL

Mosunetuzumab will be administered outpatient for all doses. During cycle 1, dose step up dosing will be administered on days 1, 8 and 15. Cycles 2 and beyond, mosunetuzumab will be administered on day 1. All cycles will be 21 days long.

Drug: Mosunetuzumab

Interventions

Mosunetuzumab DRUG

Given by injection

Also known as: Lunsumio

Phase 2 Lead-In Phase: Treatment with Mosunetuzumab Inpatient; Phase 2: Treatment with Mosunetuzuma Outpatient

Eligibility Criteria

• Age: 18 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 the following criteria apply:
• Age ≥18 years at the time of signing the Informed Consent Form
• Ability to comply with the study protocol and procedures and required
• Patients must have received ≥2 prior lines of systemic therapy, including the current BTKi
• Patients with high-risk CLL/SLL defined as the presence of any of the following factors:
• progression of disease on prior covalent BTKi, or progression of disease on or within 6 months of venetoclax-based treatment, or 3 or more prior treatments, or presence of del(17p) and/or TP53 mutation, or unmutated IGHV e. Patients with CLL/SLL on continuous BTKi therapy (covalent or non-covalent) for ≥12 months and detectable bone marrow MRD4 by ClonoSEQ f. Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 or 1 g. Adequate BM function independent of growth factor or transfusion support, within 2 weeks of screening, at screening as follows unless cytopenia is clearly due to marrow involvement of CLL:
• Platelet count ≥50,000/µL; in cases of thrombocytopenia clearly due to marrow involvement of CLL (per the discretion of the investigator), platelet count should be
• ≥30,000/mm3
• ANC ≥1.5x109 cells/L unless neutropenia is clearly due to marrow involvement of CLL (per the discretion of the investigator)
• Total hemoglobin ≥10 g/dL unless anemia is due to marrow involvement of CLL (per the discretion of the investigator) h. Adequate liver function as indicated by a total bilirubin ≤1.5 x ULN, AST, and ALT ≤3 times the institutional ULN value
• In patients with CLL involvement of the liver; AST and ALT \<5 times institutional ULN and total bilirubin \<3 times institutional ULN i. In patients with Gilbert syndrome: total bilirubin \<3 times institutional ULN j. Adequate renal function: serum creatinine ≤1.5 ULN or eGFR ≥50 mL/min k. Life expectancy \>6 months l. Resolution to Grade ≤1 for clinically significant toxicities attributable to prior therapies before commencement of the first study drug administration with the following exceptions:
• Any grade alopecia or vitiligo
• Grade 2 peripheral sensory or motor neuropathy
• Endocrinopathy managed and controlled using replacement therapy m. Patients who have a negative HIV test at screening, with the following exception.
• Patients with a positive HIV test at screening are eligible provided that, prior to enrollment, they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count ≥200/μL, have an undetectable viral load, and have not had a history of an AIDSdefining opportunistic infection within the past 12 months.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Patients with high disease burden, defined as having either absolute lymphocyte count \>5 x 109 cells/L, or largest lymph node \>2 cm, or bone marrow with \>50% CLL involvement
• Pregnant or breastfeeding or intending to become pregnant during the study or within 3 months after the final dose of mosunetuzumab and tocilizumab (if applicable). Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment. If a serum pregnancy test has not been performed within 14 days prior to receiving first study treatment, a negative urine pregnancy test result (performed within 7 days prior to study treatment) must be available.
• b. Participants who previously received any of the following treatments prior to study entry:
• Treatment with mosunetuzumab or other CD20/CD3-directed bispecific antibodies
• Allogeneic stem cell transplant within 90 days of enrollment or with active GVHD c. Participants who have received any of the following treatments, whether investigational or approved, within the respective time periods prior to initiation of study treatment:
• Radiotherapy within 2 weeks prior to the first dose of study treatment
• CAR T-cell therapy within 90 days before first study treatment
• Use of monoclonal antibodies or antibody-drug conjugates within 4 weeks prior to first study treatment d. Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to first dose of study treatment
• Systemic corticosteroid treatment ≤25 mg/day prednisone or equivalent and inhaled corticosteroids are permitted.
• Administration of acute, low-dose, systemic immunosuppressant medications (e.g., single dose of dexamethasone for nausea or B-symptoms) is permitted.
• The use of mineralocorticoids for management of orthostatic hypotension and corticosteroids for management of adrenal insufficiency is permitted. e. Any other anti-cancer therapy, whether investigational or approved, including but not limited to chemotherapy, within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to initiation of study treatment. f. Prior cancer immunotherapy not explicitly described in this protocol g. Received a live, attenuated vaccine within 4 weeks before first dose of study treatment, or in whom it is anticipated that such a live attenuated vaccine will be required during the study period or within 5 months after the final dose of study treatment h. Transformation of CLL to aggressive NHL (e.g., Richter's transformation, prolymphocytic leukemia, or diffuse large B-cell lymphoma \[DLBCL\]) or CNS involvement by CLL i. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins) j. History of prior malignancy, except for conditions as listed below if patients have recovered from the acute side effects incurred as a result of previous therapy:
• Malignancies treated with curative intent and with no known active disease present for ≥2 years before enrollment
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated cervical carcinoma in situ without evidence of disease

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

UT MD Anderson

Houston, Texas, 77030, United States

RECRUITING

Related Links

• UT MD Anderson Website

MeSH Terms

Conditions

Leukemia, Lymphoid

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Mahesh Swaminathan, MD

  UT MD Anderson

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mahesh Swaminathan, MD

CONTACT

(832) 728-8778; mswaminathan@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: April 30, 2026
• First Posted: May 5, 2026
• Study Start: July 9, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2030
• Last Updated: July 30, 2026

Record last verified: 2026-07

Locations

US (1)