Rituximab in Combination with Glofitamab and Polatuzumab Vedotin in Patients with Previously Untreated Aggressive B-cell Lymphoma Ineligible for R-CHOP

Inclusion Criteria:

1. Patient has provided written informed consent and is able and willing to comply withthe study protocol and protocol mandated treatments according to ICH and localregulations.

2. Patient is above 60 years of age

3. Patient is not eligible for a fully dosed R-CHOP

4. Patient has histologically confirmed aggressive B-cell lymphoma.

5. Patient has at least one measurable FDG PET-positive lymphoma manifestation; definedas lesional maximum FDG uptake higher than the maximum FDG uptake in unaffectedliver parenchyma as measured in a reference volume-of-interest with >10 mL

6. Baseline biopsy material is available for central review.

7. Female patients considered as women of childbearing potential (WOCBP, see section 5.2.7 for definition) and male patients with female partners considered as WOCBPmust:

8. agree to either remain completely abstinent (refrain from heterosexualintercourse) or to use at least one effective contraceptive methods thatresults in a failure rate of < 1% per year

9. refrain from donating ova (female patients) or donating sperm (male patients)

10. in case of male patients with pregnant female partners, remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as acondom to avoid exposing the embryo.

11. Patient did not receive any prior systemic lymphoma therapy.

12. Patient has an ECOG performance status of ≤ 2.

13. Patient has with treatment a life expectancy (in the opinion of the investigator) ofat least 12 weeks.

14. Patient has adequate liver function

15. Patient as adequate hematological function

16. Patient has adequate renal function

17. Patients has negative serologic and/or polymerase chain reaction (PCR) test resultsfor:

• Acute or chronic hepatitis B (HBV) infection.

• Hepatis C virus (HCV) and human immunodeficiency virus (HIV)

15. Patient has no active SARS-CoV-2 infection.

Exclusion Criteria:

Medical conditions:

1. Patient with chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) (including CD20+ ALL), lymphoblastic lymphoma, Richter's transformation, Burkittlymphoma.

2. Patient ≤ 60 years

3. Patient with known active infection, or reactivation of a latent infection, whetherbacterial (e.g., tuberculosis), viral (including, but not limited to severepneumonia, COVID-19, Epstein-Barr virus [EBV], cytomegalovirus [CMV], hepatitis B,hepatitis C, and HIV], fungal, mycobacterial, or other pathogens (excluding fungalinfections of nail beds) or any major episode of infection requiring hospitalizationor treatment with IV antibiotics (for IV antibiotics this pertains to completion oflast course of antibiotic treatment) within 4 weeks prior to study enrollment.

4. Patient with current > Grade 1 peripheral neuropathy.

5. Patient with history of confirmed progressive multifocal leukoencephalopathy (PML).

6. Patient with history of leptomeningeal disease.

7. Patient with current or history of CNS lymphoma.

8. Patient with current or history of CNS disease, such as stroke, epilepsy, CNSvasculitis, or neurodegenerative disease with exceptions.

9. Patient with another invasive malignancy in the last 2 years (with the exception ofbasal cell carcinoma and tumors deemed by the Investigator to be of low likelihoodfor recurrence), with the exception of malignancies with a negligible risk ofmetastasis or death (e.g., 5-year OS rate 90%), such as adequately-treated carcinomain situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer,ductal carcinoma in situ, or Stage I uterine cancer.

10. Patient with significant or extensive history of cardiovascular disease (such as NewYork Heart Association (NYHA) Class ≥ II cardiac disease, congestive heart failure,myocardial infarction or cerebrovascular accident within the past 3 months, unstablearrhythmias, or unstable angina or history of multiple cardiovascular events) orsignificant pulmonary disease (including obstructive pulmonary disease and historyof bronchospasm).

11. Patient with active or history of autoimmune disease or immune deficiency,including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis,systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome,Guillain-Barré syndrome, or multiple sclerosis (see addendum for a morecomprehensive list of autoimmune diseases and immune deficiencies), with exceptions.

12. Patient with uncontrolled pleural effusion, pericardial effusion, or ascitesrequiring recurrent drainage procedures (once monthly or more frequently).

13. Patient with history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g.,bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic. Prior/Concomitant Therapy:

14. Patient received treatment with any other standard anti-cancerradiotherapy/chemotherapy including investigational therapy (defined as treatmentfor which there is currently no regulatory authority approved indication) within 4weeks or five times the elimination half-life of the product, whichever is longer,prior to study enrollment.

15. Patient with prior solid organ transplantation.

16. Patient with prior allogeneic stem cell transplantation.

17. Patient with prior treatment with targeted therapies (e.g., tyrosine kinaseinhibitors, systemic immunotherapeutic/immunostimulating agents, including, but notlimited to, CD137 agonists or immune checkpoint blockade therapies, includinganti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies,radio-immunoconjugates, antibody-drug conjugates, immune/cytokines, and monoclonalantibodies) within 4 weeks or five half-lives of the drug, whichever is shorter,prior to study enrollment.

18. Patient with toxicities from prior anti-cancer therapy including immunotherapy thatdid not resolve to ≤ Grade 1 except for alopecia, endocrinopathy managed withreplacement therapy and stable vitiligo.

19. Patient with any history of immune related ≥ Grade 3 AE except for endocrinopathymanaged with replacement therapy.

20. Patient with ongoing corticosteroid use 25 mg/day of prednisone or equivalent within 4 weeks prior and during study treatment.

21. Patient with treatment with systemic immunosuppressive medication (including, butnot limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, andanti-TNF agents) within 2 weeks prior to initiation of study treatment, oranticipation of need for systemic immunosuppressive medication during studytreatment, with exceptions.

22. Patient who received administration of a live, attenuated vaccine within 4 weeksprior to study enrollment infusion or anticipation that such a live, attenuatedvaccine will be required during the study or within 5 months after the last dose ofstudy treatment. Other Exclusions:

23. Patient with history of illicit drug or alcohol abuse within 12 months prior toscreening, in the Investigator's judgment.

24. Patient with history of severe allergic anaphylactic reactions to chimeric orhumanized monoclonal antibodies or recombinant antibody-related fusion proteins.

25. Patient with known hypersensitivity to Chinese hamster ovary (CHO) cell products orto any component of the rituximab, obinutuzumab, polatuzumab vedotin and/orglofitamab formulation and/or to the contrast agents used in the study.

26. Female patient is pregnant or breast feeding. Female patients of childbearingpotential must have a negative serum pregnancy test result within 7 days prior toinitiation of study treatment.

27. Patient who has been incarcerated or involuntarily institutionalized by court orderor by the authorities.

28. Patients who are unable to consent because they do not understand the nature,significance and implications of the clinical trial and therefore cannot form arational intention in the light of the facts.

29. Patients who are dependent on the sponsor, the investigator or the trial site.