Chemotherapy-Free combo aims to tackle Hard-to-Treat lymphoma

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Histologically proven DLBCL 2. Relapsed or refractory disease after first-line chemoimmunotherapy containing both rituximab and anthracycline A.Refractory disease defined as no complete remission to first-line therapy; subjects who are intolerant to first-line therapy are excluded * Progressive disease (PD) as best response to first-line therapy * Stable disease (SD) as best response after at least 4 cycles of first-line therapy * Partial response (PR) as best response after at least 6 cycles, and biopsy-proven residual disease or disease B.Relapsed disease defined as complete remission to first-line therapy followed by biopsy- proven disease relapse ≤ 12 months of initiating first-line therapy 3. Signed Informed Consent Form 4. Age ≥ 19 years at the time of signing Informed Consent Form and willingness to comply with study protocol procedures 5. Life expectancy ≥ 12 weeks 6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2 7. At least one bi-dimensionally measurable (≥ 1.5 cm) nodal lesion, or one bi-dimensionally measurable (≥ 1 cm) extranodal lesion, as measured on CT scan 8. Negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test within 7 days prior to enrollment 9. Negative HIV test at screening, with the following exception: i.Individuals with a positive HIV test at screening are eligible provided, prior to enrollment, they are stable on antiretroviral therapy, have a CD4 count ≥ 200/µL, and have an undetectable viral load. 10. For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agree to refrain from donating eggs, as defined below: i.Female participants must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for at least 18 months after pretreatment with obinutuzumab, 2 months after the final dose of glofitamab, 9 months after the final dose of polatuzumab vedotin, and 3 months after the final dose of tocilizumab (as applicable), whichever is longer. Women must refrain from donating eggs during this same period ii.A female participant is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a female participant with tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. iii.Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method. iv.The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form. 11. For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agree to refrain from donating sperm, as defined below: i.With a female partner of childbearing potential or pregnant female partners, male participants must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for at least 3 months after pretreatment with obinutuzumab, 2 months after the final dose of glofitamab, 6 months after the final dose of polatuzumab vedotin, or 2 months after the last dose of tocilizumab (as applicable), whichever is longer. Male participants must refrain from donating sperm during this same period. ii.The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form. 12. Adequate hematologic function (unless due to underlying disease, as established for example, by extensive bone marrow involvement or due to hypersplenism secondary to involvement of the spleen by LBCL per the investigator for which blood product transfusions are permitted) defined as follows: * Hemoglobin ≥ 9.0 g/dL without packed RBC transfusion during 7 days before first treatment. * ANC ≥1.0x109/L * Platelet count ≥75 x 109/L 13. Adequate renal function, defined as measured or estimated creatinine clearance ≥50 mL/min Exclusion Criteria: Patients who meet any of the following criteria will be excluded from study entry: Contraindication to any of the individual components of glofitamab or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products 1. Prior solid organ transplantation 2. Prior treatment with a regimen containing polatuzumab vedotin or glofitamab 3. Prior treatment with systemic immunotherapeutic agents, including but not limited to, radio-immuno-conjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (mAbs) (e.g., anti-cytotoxic T lymphocyte associated protein 4, anti-PD-1, and anti-PD-L1) within 4 weeks or five half-lives of the drug, whichever is shorter 4. Prior use of any monoclonal antibody for the purposes of treating cancer within 3 months of the start of Cycle 1 5. Any investigational therapy for the purposes of treating cancer within 28 days prior to the start of Cycle 1 6. Prior radiotherapy to the mediastinal/pericardial region(Radiotherapy to non-target lesion sites will be permitted.) 7. Current Grade \> 1 peripheral neuropathy 8. Corticosteroid use \> 50 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control i.Participants receiving corticosteroid treatment with ≤ 50 mg/day of prednisone or equivalent for reasons other than lymphoma symptom control (e.g., rheumatoid arthritis) must be documented to be on a stable dose of at least 4 weeks duration prior to the start of Cycle 1. * Corticosteroid therapy for control of cancer symptoms or side effects of prior treatment (e.g., nausea or B-symptoms) is permitted * The use of inhaled corticosteroids is permitted. * The use of mineralocorticoids for management of orthostatic hypotension is permitted. * The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted. ii.Participants who require lymphoma symptom control during screening may receive steroids in the following manner: * Up to 50 mg/day of prednisone or equivalent may be used for lymphoma symptom control during screening, including prior to finalization of staging (not included as part of pre-phase treatment). * If glucocorticoid treatment is urgently required at higher doses for lymphoma symptom control prior to the start of study treatment, tumor assessments must be completed prior to initiation of \> 30-100 mg/day of prednisone or equivalent. Prednisone \> 30-100 mg/day or equivalent may be given for a maximum of 10-14 days as a pre-phase treatment. As part of the pre-phase treatment, vincristine may not be administered. 9. History of other malignancy that could affect compliance with the protocol or interpretation of results: i.Participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study are eligible. ii.Participants with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for ≤ 2 years prior to enrollment are eligible. iii.Participants with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible. 10. Significant or extensive history of cardiovascular disease such as New York Heart Association Class III or IV cardiac disease or Objective Assessment Class C or D, myocardial infarction within the last 3 months prior to the start of Cycle 1, unstable arrhythmias, or unstable angina 11. Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis 12. Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis or neurodegenerative disease i.Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurological deficits, as judged by the investigator, are allowed. 13. Current or past history of CNS lymphoma 14. Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) 15. Current or past history of Waldenström macroglobulinemia 16. History or presence of an abnormal ECG that is clinically significant in the investigator's opinion 17. Patients with known or suspected active infection, or reactivation of a latent infection, whether bacterial, viral (including, but not limited to, SARS-Cov-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B, and hepatitis C), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 4 weeks of dosing 18. History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows: i.Grade ≥ 3 adverse events with the exception of Grade 3 endocrinopathy managed with replacement therapy. ii.Grade 1/2 adverse events that did not resolve to baseline after treatment discontinuation. 19. History of autoimmune disease, including but not limited to 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 i.Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. ii.Participants with a history of disease-related immune thrombocytopenic purpura or autoimmune hemolytic anemia may be eligible for this study. iii.Participants with controlled Type I diabetes mellitus who are on an insulin regimen are eligible for the study. iv.Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible (e.g., participants with psoriatic arthritis are excluded) if all the following conditions are met: * Rash covers \< 10% of body surface area. * Disease is well controlled for the last 12 months and requires only low-potency topical corticosteroids. 20. Clinically significant liver disease, including active viral or other hepatitis or cirrhosis 21. Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment 22. Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma): * INR or PT \>1.5 Xupper limit of normal (ULN) in the absence of therapeutic anticoagulation. * PTT or aPTT \> 1.5 XULN in the absence of a lupus anticoagulant. * Serum AST and ALT ≥ 2.5 XULN * Total bilirubin ≥ 1.5XULN Participants with documented Gilbert disease may be enrolled if total bilirubin is ≤ 3.0XULN 23. Live, attenuated vaccine within 4 weeks before study treatment infusion on Day 1 of Cycle 1 or anticipation that such a live, attenuated vaccine will be required during the study. Live vaccines during the study and until participants B cells recover, are prohibited Influenza vaccination should be given during influenza season only. Participants must not receive live, attenuated influenza vaccine at any time during the study treatment period. 24. Suspected active or latent tuberculosis (as confirmed by a positive interferon-gamma release assay) 25. Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen \[HBsAg\] serology) Participants with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus (HBV) DNA is undetectable at the time of screening. Such participants must be willing to undergo HBV DNA testing on Day 1 of every cycle and every 3 months for at least 12 months after the final cycle of study treatment and appropriate antiviral therapy as indicated. 26. Positive test results for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing) Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. 27. Participants with a history of progressive multifocal leukoencephalopathy 28. Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 18 months after pretreatment with obinutuzumab or 2 months after the final dose of glofitamab, whichever is longer 29. Positive SARS-CoV-2 test within 7 days prior to enrollment. Rapid antigen test result is also acceptable