Inclusion Criteria:
1. Able to provide written informed consent forms approved by the National Ethics Committee (NEC) prior to the initiation of any screening or study-specific procedures and able to understand and to comply with the requirements of the study and the schedule of assessments.
2. Histologically confirmed MCL after CAR T-cells failure (CD20+ by flow cytometry or immunohistochemistry). Note: Availability of archival material is mandatory for the study to perform central pathology review. Central pathology confirmation is not required to start treatment.
3. Age ≥ 18.
4. Patients who received CAR T-cells therapy for R/R MCL at least 1 month prior to study entry (30 days, D+30).
5. Patients not achieving a CR after CAR-T cells and any of the following criteria:
* Stable disease (SD) or progressive disease (PD) up to D+90 after CAR T-cells infusion (from D+30 to D+90);
* Partial response (PR) at D+90 after CAR-T cells infusion;
* Relapsed disease at any time after CAR-T cells infusion.
6. No persistent CAR-T neurotoxicity symptoms or previous experience during CAR T-cells therapy of severe neurotoxicity grade \> 3
7. Adverse events from prior anti-cancer therapy must have resolved to Grade ≤ 1 (hematological toxicities excepted).
8. Adequate hematological counts are defined as follows:
* Absolute neutrophil count (ANC) \> 1.0 x 109/L unless due to bone marrow involvement by lymphoma;
* Platelet count ≥ 50.000/mm3 unless due to bone marrow involvement by lymphoma;
* Hemoglobin ≥ 8.0 g/dL.
9. Adequate renal function defined as follows:
\- Creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula).
10. Adequate hepatic function per local laboratory reference range as follows (unless due to lymphoma):
* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN;
* Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin).
11. Participants must be able to adhere to the study visit schedule and other protocol requirements.
12. Life expectancy \> 12 weeks.
13. ECOG Performance Status of 0, 1, or 2.
14. Women of childbearing potential must have a negative pregnancy test at screening.
15. Women of childbearing potential must take necessary precautions to avoid pregnancy while receiving study treatments and for 2 months after the last dose of glofitamab, for 18 months after the last dose of obinutuzumab and for 3 months after the last dose of tocilizumab.
16. Male patient with a female partner of childbearing potential must agree to use an acceptable method of contraception for the duration of the study and for 2 months after the last dose of glofitamab, for 3 months after the last dose of obinutuzumab and for 2 months after the last dose of tocilizumab.
Exclusion Criteria:
1. Prior exposure to an anti-CD20xCD3 bispecific antibody (bsAbs).
2. Participants not able to give consent.
3. Relapsing or progressing disease within 1 month (30 days) after CAR T-cells therapy.
4. History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows:
* Grade ≥ 3 adverse events except for Grade 3 endocrinopathy managed with replacement therapy;
* Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation.
5. Patients with history of macrophage activation syndrome (MAS) / hemophagocytic lymphohistiocytosis (HLH).
6. Allogeneic hematopoietic stem cell transplantation.
7. History of progressive multifocal leukoencephalopathy (PML).
8. History of autoimmune disease, including, but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
9. CNS involvement with lymphoma.
10. Participant has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to the first dose of study drug.
11. Cardiovascular disease \[NYHA class ≥2\].
12. Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent.
13. Evidence of other clinically significant uncontrolled condition(s) included, but not limited to:
1. Uncontrolled and/or active systemic infection (viral, bacterial or fungal), including active ongoing infection from SARS-CoV-2;
2. Chronic or acute hepatitis B virus (HBV) or hepatitis C (HCV) require treatment. Note: participants with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen (Ag) negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from previous infection or intravenous immunoglobulins (IVIG) may participate; inactive carriers (HBsAg positive with undetectable HBV- DNA) are eligible. Patients with presence of HCV antibody are eligible only if PCR negative for HCV-RNA;
14. HIV seropositivity.
15. If female, the patient is pregnant or breast-feeding.
