BrUOG-401 is a prospective, single-arm, phase 2 trial of first-line therapy in adult patients
with previously untreated FL or MZL. All patients will be assigned the same initial treatment
plan, modified by interim response assessment (IRA) after Cycle 4. All patients will start
treatment with four 21-day cycles (C1-4) of mosunetuzumab alone (using step-up dosing during
C1), followed by IRA. Patients who achieve CR at IRA will continue with additional 4 cycles
(C5-8) of mosunetuzumab. Patients who achieve PR at IRA will receive mosunetuzumab with
lenalidomide augmentation during C5-8. Primary response assessment (PRA) will occur after C8.
Patients who remain in PR at PRA will continue for additional 4 cycles (extended
1. Ability to understand and the willingness to sign a written informed consent document
and to comply with the study protocol procedures.
2. Age ≥18 years at the time of signing informed consent. Because no dosing or adverse
event data are currently available on the use of mosunetuzumab in patients <18 years
of age, they are excluded from this study.
3. Histologically confirmed diagnosis of:
- follicular lymphoma (grade 1, 2, 3a, or not otherwise specified) or
- marginal zone lymphoma (nodal, extranodal, or splenic), according to 2016 WHO
classification and confirmed to express the CD20 antigen by immunohistochemistry
or flow cytometry. Patients in whom definitive pathologic subtype of FL/MZL is
undetermined due to limited biopsy material can be enrolled if in the
investigator's opinion integrated clinicopathologic data are consistent with the
4. Agreement to provide, if available, lymphoma tissue for correlative analyses.
5. At least one bi-dimensionally measurable nodal lesion, defined as >1.5 cm in its
longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as
>1.0 cm in its longest diameter; with the exception of splenic MZL, which must be
evaluable using the International SMZL Group criteria.76,88,89
6. No prior systemic therapy for B-cell lymphoma, except for palliative corticosteroids;
prior radiation therapy is allowed.
7. Indication to start systemic therapy for lymphoma, in the investigator's judgement.
Patients with low burden of disease are eligible if they desire therapy; asymptomatic
patients should thoroughly understand the risks and benefits of lymphoma-directed
therapy versus watchful waiting.
8. Performance status ECOG 0, 1, or 2.
9. Adequate hematologic function (unless due to underlying lymphoma as established by
bone marrow involvement or splenomegaly):
- hemoglobin ≥9 g/dL,
- absolute neutrophil count ≥1.0 x 109/L,
- platelet count ≥75 x 109/L.
10. Glomerular filtration rate (GFR) ≥40 mL/min/1.73m2 using the Mayo Quadratic Formula.
11. The effects of mosunetuzumab on the developing human fetus are unknown. For this
reason and because lenalidomide used in this trial is known to be teratogenic, women
of child-bearing potential and men must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) and refrain from donating eggs or
sperm throughout the treatment and for 3 months after the last dose of trial therapy.
Should a woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately.
1. Grade 3b follicular lymphoma or transformed lymphoma.
2. Prior treatment with any anti-CD20 antibody or lenalidomide.
3. Prior stem cell transplantation (autologous or allogeneic) or prior solid organ
4. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
antibodies or known sensitivity or allergy to murine products.
5. Known NYHA class 3/4 congestive heart failure, LVEF <40%, myocardial infarction within
6 months prior to enrollment, unstable angina, or unstable arrhythmia.
6. Chronic obstructive pulmonary disease (COPD) requiring oral corticosteroids or chronic
7. History of autoimmune disease, including, but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, idiopathic pulmonary fibrosis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
syndrome, granulomatosis with polyangiitis, Guillain-Barré syndrome, multiple
sclerosis, vasculitis, or glomerulonephritis, with the exception of: hypothyroidism
(on stable dose of thyroid replacement therapy), asthma managed with inhaled
medications only; type 1 diabetes mellitus on stable insulin regimen, Sjögren
syndrome, immune thrombocytopenia or autoimmune hemolytic anemia that does not require
systemic therapy; dermatologic condition (including eczema, psoriasis, lichen simplex
chronicus, or vitiligo) with skin manifestations with rash covering <10% of body
surface area and not requiring treatment other than low-potency topical
corticosteroids for >12 months prior to registration.
8. Use of any systemic immunosuppressive medications (including, but not limited to,
cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
factor agents) with the exception of corticosteroid treatment using <10 mg/day
prednisone or equivalent within 2 weeks prior to first treatment; a brief course of
palliative corticosteroids at higher doses (prednisone up to 100 mg daily, for up to 7
days) is allowed, but must be completed at least 7 days before the first dose of
9. Any of the following conditions:
- active bacterial infection requiring antibiotics
- known or suspected chronic active Epstein Barr virus (CAEBV) infection
- history of hemophagocytic lymphohistiocytosis (HLH)
- confirmed progressive multifocal leukoencephalopathy (PML)
- EBV or CMV viremia
- positive test for hepatitis B surface antigen (HBSAg). Patients with a positive
total/IgG hepatitis B core antibody (HBcAb) may participate if hepatitis B virus
(HBV) DNA is undetectable at screening, if they agree to take entecavir or
tenofovir, and undergo periodic DNA testing
- positive hepatitis C virus (HCV) antibody, unless a negative polymerase chain
reaction (PCR) for HCV is documented
- positive test for HIV.
10. Administration of a live, attenuated vaccine within 4 weeks before first mosunetuzumab
dose or anticipation that such a live, attenuated vaccine will be required during the
11. Current or past history of CNS disease, including stroke, epilepsy, or CNS vasculitis,
or an advanced neurodegenerative disease; with the exception of: stroke >2 years
before registration without any residual neurologic deficits and no subsequent
transient ischemic attacks; history of epilepsy with no seizures for >2 years and not
using any antiepileptic therapy; well-controlled Parkinson's disease (with no need for
medication adjustment for >6 months).
12. History of other malignancy that could affect compliance with the protocol or
interpretation of results; patients with a curatively treated skin cancer, in situ
cervical cancer, or another malignancy treated curatively with a documented remission
>2 years before registration are eligible.
13. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
(excluding fungal infections of nail beds) at study enrollment or any major episode of
infection requiring treatment with IV antibiotics or hospitalization within 4 weeks
before the first dose of mosunetuzumab.
14. Clinically significant liver disease, including viral or other hepatitis, current
alcohol abuse, or cirrhosis.
15. Any major surgery within 4 weeks before the first dose of mosunetuzumab, other than
lymph node biopsy for diagnosis.
16. Evidence of other significant or uncontrolled medical or psychiatric conditions that
could affect compliance with the protocol.
17. Any of the following abnormal laboratory values within 14 days prior to first dose of
- AST or ALT >3x ULN
- total bilirubin >2 x ULN (unless due to Gilbert syndrome with indirect
- INR>1.5 x ULN without anticoagulation
- PTT or APTT >1.5x ULN in the absence of lupus anticoagulant.
18. Any radiation therapy within 2 weeks prior to first dose of mosunetuzumab.
19. Pregnancy, breast-feeding, or prisoner status. Women of childbearing potential must
have a negative pregnancy test within 2 weeks before first dose of mosunetuzumab.