This is a multi-center, open-label, interventional clinical trial designed to evaluate the efficacy and safety of subcutaneous (SC) Mosunetuzumab as a first-line immunotherapy in patients with low tumor burden follicular lymphoma (LTB-FL), defined by the absence of GELF criteria.
at least 18 years old
Histologically confirmed classic FL (cFL) (according to WHO-HEAM4R classification)
Low tumor burden by GELF criteria
No prior therapy except surgery or radiotherapy for disease that was previously localized
1. An active viral infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) defined by detectable viral DNA in the blood by PCR. Patients with HIV are eligible provided an undetectable viral load and a CD4 count > 200 cell/mcl
Total Bilirubin or GGT or AST or ALT > 3 X ULN.
Creatinine Clearance calculated by Cockcroft and Gault Formula < 40 ml/min
Presence or history of CNS involvement by lymphoma
Single group
Mosunetuzumab is a bispecific monoclonal antibody targeting CD20 on B cells and CD3 on T cells, redirecting T cells to eliminate malignant B cells.
DrugIn this study, Mosunetuzumab will be administered subcutaneously over 8 treatment cycles: 5 mg on Day 1 of Cycle 1, followed by 45 mg in all subsequent cycles.
Overall Response Rate-ORR Overall response rate (ORR) at the end of treatment (6 months) using the Lugano criteria
ORR is defined as the proportion of patients who achieved Complete Response or Partial Response determined by Lugano 2014 criteria as assessed by investigators at 6 months after initiation of treatment and prior to the initiation of any subsequent anti-lymphoma therapy. Patients without post-baseline disease assessments will be considered non-responders.
Progression Free Survival -PFS
PFS is defined as the time in months from the first dose of study drug to disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause. Surviving patients without disease progression will be censored at the time of the last adequate disease assessment. Surviving subjects without post-baseline disease assessment will be censored at the date of first dose of study drug.
Duration of response -DOR
DOR is defined for patients who achieved Complete Response (CR) or Partial Response (PR) ('responders'), as the time in months from initial CR/PR to disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause. Surviving responders without radiographic disease progression will be censored at the time of the last adequate disease assessment
Complete Response Rate - CRR - Lymphoma (FACT-Lym) subscale.
CRR is defined as the proportion of patients who achieved Complete Response, determined by Lugano 2014 criteria as assessed by the investigator. All responses of Complete Response after initiation of subsequent anti-lymphoma therapy will be excluded. Subjects without post-baseline disease assessments will be considered as not achieving Complete Response.
Duration of Complete Response -DOCR
DOCR is defined for patients who achieved Complete Response, as the time in months from initial CR/PR to disease progression determined by Lugano 2014 criteria as assessed by investigator, or death from any cause. Surviving responders without radiographic disease progression will be censored at the time of the last adequate disease assessment.
Exploratory Biomarker Research Endpoints: Longitudinal measurement of ctDNA in the peripheral blood (PB), before and during treatment, at disease progression, at CR and one year after achievement of CR, as a biomarker for long-term remission
Longitudinal measurement of ctDNA in the peripheral blood (PB), before and during treatment, at disease progression, at CR and one year after achievement of CR, as a biomarker for long-term remission;
Exploratory Biomarker Research Endpoints:
Evaluating the treatment-induced dynamics and molecular signatures of the non-tumor lymphocytic and myeloid compartments in peripheral blood, before and during treatment, at disease progression, at CR and one year after achievement of CR by performing consecutive flow cytometry, single cell RNA sequencing (scRNA-seq) and epigenetic studies, and correlation with outcome;
Exploratory Biomarker Research Endpoints:
Analyzing tumor microenvironment (TME) in lymph nodes pre-treatment at disease progression, at CR and one year after achievement of CR by performing scRNA-seq;
Exploratory Biomarker Research Endpoints
Evaluating the association between patient's microbiome and response to treatment
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Tel-Aviv Sourasky Medical Center
Lead sponsor
Hoffmann-La Roche
Collaborator
