Mosunetuzumab in Combination With Platinum-Based Salvage Chemotherapy in Patients With Relapsed/Refractory Aggressive B Cell Lymphoma

NCT05464329 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202209113
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two-arm, open-label, phase Ib single-site study with expansion cohorts testing the addition of mosunetuzumab to intensive platinum-based salvage chemotherapy in patients with relapsed/refractory aggressive B cell lymphoma. The hypothesis of this study is that mosunetuzumab can be safely combined with platinum-based salvage chemotherapy in this patient population, and that this approach may outperform chemoimmunotherapy approaches that instead incorporate rituximab retreatment. The enrolling physician's choice of the chemotherapy backbone will determine a patient's assigned study arm (Arm A = DHAX, Arm B = ICE). The two arms will accrue patients to phase Ib independently.

Conditions

Large B-cell Lymphoma; High-grade B-cell Lymphoma; Transformed B-Cell Lymphoma; Follicular Lymphoma Grade 3B

Keywords

Aggressive B cell lymphoma; Transformed B cell lymphoma; Follicular lymphoma grade 3B; Anti-CD3; Anti-CD20; Bispecific antibody

Outcome Measures

Primary Outcomes (2)

• Frequencies and grades of treatment-emergent adverse events (TEAEs)

  -Treatment-emergent adverse events (TEAE) are defined as adverse events possibly, probably, or definitely related to mosunetuzumab that occur on or after first dose of study treatment.

  From start of treatment through 30 days after administration of study treatment, or until initiation of alternate treatment for lymphoma, whichever occurs earlier (estimated to be 16 weeks)

• Rate of treatment delay or discontinuation due to treatment-emergent adverse events (TEAEs)

  -Treatment-emergent adverse events (TEAE) are defined as adverse events possibly, probably, or definitely related to mosunetuzumab that occur on or after first dose of study treatment.

  From start of treatment through 30 days after administration of study treatment, or until initiation of alternate treatment for lymphoma, whichever occurs earlier (estimated to be 12 weeks)

Secondary Outcomes (13)

• Number of participants with complete response (CR)

  After cycle 2 (each cycle is 21 days; estimated to be 42 days)

• Number of participants with partial response (PR)

  After cycle 2 (each cycle is 21 days; estimated to be 42 days)

• Overall response rate (ORR)

  After cycle 2 (each cycle is 21 days; estimated to be 42 days)

• Number of participants with stable disease (SD)

  After cycle 2 (each cycle is 21 days; estimated to be 42 days)

• Number of participants with progressive disease (PD)

  After cycle 2 (each cycle is 21 days; estimated to be 42 days)

Study Arms (2)

Arm A: Mosunetuzumab + DHAX

EXPERIMENTAL

* 4 cycles (cycle=21 days) of mosunetuzumab with DHAX salvage chemotherapy (selected at the discretion of the treating physician). * For patients tolerating Cycle 1 with step-up of treatment, Cycles 2 and beyond will consist of mosunetuzumab administered as a single dose on Day 1 along with DHAX. Patients will undergo PET-CT restaging prior to Cycle 3. Patients with SD or PD based on restaging after Cycle 2 will discontinue study treatment; further treatment will be administered at the discretion of the treating physician. Patients responding to study treatment based on restaging after Cycle 2 may receive up to two additional cycles of study treatment before consolidation therapy (e.g., autologous stem cell transplantation, chimeric antigen receptor T-cell therapy) at the discretion of the treating physician.

Drug: Mosunetuzumab; Drug: DHAX

Arm B: Mosunetuzumab + ICE

EXPERIMENTAL

* 4 cycles (cycle=21 days) of mosunetuzumab with ICE salvage chemotherapy (selected at the discretion of the treating physician). * For patients tolerating Cycle 1 with step-up of treatment, Cycles 2 and beyond will consist of mosunetuzumab administered as a single dose on Day 1 along with ICE. Patients will undergo PET-CT restaging prior to Cycle 3. Patients with SD or PD based on restaging after Cycle 2 will discontinue study treatment; further treatment will be administered at the discretion of the treating physician. Patients responding to study treatment based on restaging after Cycle 2 may receive up to two additional cycles of study treatment before consolidation therapy (e.g., autologous stem cell transplantation, chimeric antigen receptor T-cell therapy) at the discretion of the treating physician.

Drug: Mosunetuzumab; Drug: ICE

Interventions

Mosunetuzumab DRUG

Provided by Genentech.

Also known as: RO7030816, BTCT4465A

Arm A: Mosunetuzumab + DHAX; Arm B: Mosunetuzumab + ICE

DHAX DRUG

-Standard of care. Flexibility in administration is permitted at the discretion of the treating physician.

Arm A: Mosunetuzumab + DHAX

ICE DRUG

-Standard of care. Flexibility in administration is permitted at the discretion of the treating physician.

Arm B: Mosunetuzumab + ICE

Eligibility Criteria

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

You may qualify if:

• Diagnosis of large, high-grade, or transformed B cell lymphoma or follicular lymphoma grade 3B that is refractory to or has relapsed after anti-CD20 mAb plus anthracycline-containing combination chemotherapy. A biopsy immediately prior to enrollment is not mandatory.
• Must have received at least one prior line of systemic treatment containing conventional cytotoxic chemotherapy for lymphoma. Conventional cytotoxic chemotherapy with or without an anti-CD20 mAb for prior/underlying indolent NHL (with or without maintenance/extended-use anti-CD20 mAb) will count as one line of systemic therapy.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Adequate hematologic function (unless due to underlying lymphoma per the investigator), defined as follows:
• Absolute neutrophil count ≥ 1,000/mcL
• Platelets ≥ 75,000/mcL without platelet transfusion within 14 days prior to the first dose of mosunetuzumab
• Hemoglobin ≥ 8 g/dL without red blood cell transfusion within 7 days prior to the first dose of mosunetuzumab
• Patients with extensive bone marrow involvement by lymphoma and/or disease-related cytopenias (e.g., immune thrombocytopenia) may be enrolled if the following criteria are met:
• Absolute neutrophil count ≥ 500/mcL
• Platelet count ≥ 50,000/mcL without platelet transfusion within 14 days prior to the first dose of mosunetuzumab
• No red blood cell transfusion within 7 days prior to the first dose of mosunetuzumab
• Normal laboratory values:
• Serum total bilirubin ≤ 1.5 x IULN (or ≤ 3 x IULN for patients with Gilbert's syndrome)
• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

You may not qualify if:

• Known history of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents.
• Known history of macrophage activation syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH).
• Prior allogeneic stem cell transplant.
• Treatment with radiotherapy within 2 weeks prior to the first dose of mosunetuzumab (otherwise one measurable lesion outside of the radiation field must remain).
• Prior treatment with CAR-T cell therapy within 30 days of first dose of mosunetuzumab.
• Any history of lymphomatous involvement of the CNS. Note: If CSF studies via lumbar puncture and/or neuroimaging are performed per physician discretion to rule out CNS involvement given active CNS signs or symptoms, these assessments should be completed within 6 weeks prior to study enrollment. There are no restrictions on the timing of CSF studies via lumbar puncture and/or neuroimaging performed for routine staging of patients without CNS signs or symptoms, or if performed for reasons unrelated to lymphoma evaluation.
• Current or recent history (within the last 6 months) of clinically relevant CNS disease or pathology, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
• Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to grade ≤ 1 per NCI CTCAE v 5.0 prior to Day 1 of Cycle 1.
• Treatment with systemic immunosuppressive medications, including but not limited to prednisone (\> 20 mg), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1.
• Note: The use of inhaled corticosteroids, mineralocorticoids for management of orthostatic hypotension, and single dose dexamethasone for nausea or B symptoms is permitted.
• History of solid organ transplantation.
• History of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies (mAbs).
• Known hypersensitivity to biopharmaceuticals produced in CHO cells or any component of the mosunetuzumab formulation, including mannitol.
• History of erythema multiforme, grade ≥ 3 rash, or blistering following prior treatment with immunomodulatory derivatives.
• Known active bacterial, viral, fungal, or other infection, or any major episode of infection requiring treatment with IV antibiotics within 1 week of Day 1 of Cycle 1.

Sponsors & Collaborators

• Genentech, Inc.: collaborator
• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Interventions

Ice

Intervention Hierarchy (Ancestors)

Water; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Weather; Meteorological Concepts; Environment and Public Health

Study Officials

• David Russler-Germain, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2022
• First Posted: July 19, 2022
• Study Start: January 3, 2023
• Primary Completion: January 2, 2026
• Study Completion (Estimated): October 16, 2029
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)