A Study to Evaluate the Safety and Anti-cancer Activity of Loncastuximab Tesirine in Combination With Other Anti-cancer Agents in Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (LOTIS-7)

Inclusion Criteria:

• Male or female participant aged 18 years or older

• Pathologic diagnosis of relapsed (disease that has recurred following a response) orrefractory (disease that failed to respond to prior therapy) B-NHL (2016 WorldHealth Organization classification) who have failed, or been intolerant to anyapproved therapy and had received at least two systemic treatment regimens in Part 1; and at least one systemic treatment regimen in Part 2

• LBCL:

Part 2 Arm E enrollment focused on LBCL only

• DLBCL, not otherwise specified (NOS)

• Germinal Center B-cell type

• Activated B-cell type

• Transformed FL (note: patients with transformed FL must have received at least oneline of systemic therapy post-transformation to be eligible)

• HGBCL, with MYC and BCL2 and/or BCL6 rearrangements

• HGBCL, NOS

• FL Grade 3b

• Arm F and Part 1 Arm E:

• All LBCL histologies listed above

• FL (Grade 1-3a)

• MZL

• For Arm C only:

• All histologies listed above

• DLBCL (including transformed diseases)

• MCL

• BL

• Life expectancy of at least 24 weeks according to Investigator's judgement

• Need of systemic treatment for any of the listed indications as assessed by theinvestigator, including indolent B-NHLs (e.g. FL and MZL)

• Measurable disease as defined by the 2014 Lugano Classification

• Availability of formalin-fixed paraffin-embedded tumor tissue block

• ECOG performance status 0 to 2

• Adequate organ function

• Women of childbearing potential (WOCBP) must agree to use a highly effectivemethod of contraception from the time of giving informed consent until at least 10 months after the last dose of loncastuximab tesirine. Men with femalepartners who are of childbearing potential must agree to use a condom whensexually active or practice total abstinence from the time of giving informedconsent the first dose until at least 7 months after the last dose ofloncastuximab tesirine. Men must refrain from donating sperm during this sameperiod. Arm E: WOCBP must agree to use contraceptive methods that result in afailure of less than 1% per year or remain abstinent (refrain from heterosexualintercourse) during the treatment period and for at least 18 months afterpretreatment with obinutuzumab. Arm F: WOCBP must agree to use contraceptivemethods that result in a failure of less than 1% per year or remain abstinent (refrain from heterosexual intercourse) during the treatment period and for atleast 3 months after the final dose of mosunetuzumab and tocilizumab (ifapplicable)

• Patients 80 years of age and older at the time of signing the informed consentmust be deemed fit by Cumulative Illness Rating Scale - Geriatric (CIRS-Gscale), defined as no score of 3-4 in any category AND < 5 categories with ascore of 2 excluding hematologic criteria

Exclusion Criteria:

• Known history of hypersensitivity resulting in treatment discontinuation to orpositive serum human ADA to a CD19 antibody

• Previous therapy with loncastuximab tesirine

• Previous treatment with polatuzumab vedotin, glofitamab or mosunetuzumab (applied torelevant arm and/or cohort of the specific drug administered)

• Participants who received previous treatment of polatuzumab vedotin containingregimen will be excluded from Arm C

• Participants who received previous treatment of glofitamab containing regimenwill be excluded from Arm E

• Participants who received previous treatment of mosunetuzumab containingregimen will be excluded from Arm F

• Human immunodeficiency virus (HIV) seropositive

• Serologic evidence of chronic hepatitis B virus (HBV) infection and unable orunwilling to receive standard prophylactic antiviral therapy or with detectable HBVviral load

• Serologic evidence of hepatitis C virus (HCV) infection without completion ofcurative treatment or with detectable HCV viral load

• History of confirmed progressive multifocal leukoencephalopathy

• History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or macrophageactivation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH)

• Clinically significant third space fluid accumulation (i.e., ascites requiringdrainage or pleural effusion that is either requiring drainage or associated withshortness of breath)

• Breastfeeding or pregnant

• Significant medical comorbidities

• Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, within 14 days prior to start of study drugs (C1 D1), unless approved by the Sponsor

• Live vaccine within 4 weeks prior to C1D1

• Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from acute non-hematologic toxicity (excluding alopecia) due toprevious therapy prior to screening

• Active second primary malignancy other than non-melanoma skin cancers,non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinomain situ of the breast, or other malignancy that the Sponsor's medical monitor andInvestigator agree and document should not be exclusionary

Extra Exclusion Criteria for Arms E (includes glofitamab) and F (includes mosunetuzumab) Note: as applicable, the arm-specific exclusion criteria may supersede the general ones, such as stem cell transplant.

• Prior allogeneic stem cell transplant and solid organ transplant

• Autologous stem cell transplant within 100 days prior to C1D1

• History of central nervous system (CNS) lymphoma or leptomeningeal infiltration

• Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, orneurodegenerative disease

• Known active infection, reactivation of a latent infection, whether bacterial,viral, fungal, mycobacterial, or other pathogens (excluding fungal infections ofnail beds), or any major episode of infection requiring hospitalization or treatmentwith intravenous (IV) antibiotics within four weeks prior to C1D1

• Active or history of autoimmune disease or immune deficiency, motor neuropathyconsidered of autoimmune origin and other CNS autoimmune diseases, including but notlimited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupuserythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipidantibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barrésyndrome, or multiple sclerosis, with, with certain exceptions

• Prior treatment with anti-cancer/lymphoma targeted therapies (e.g., tyrosine kinaseinhibitors, systemic immunotherapeutic/immunostimulating agents, including, but notlimited to, cluster of differentiation 137 agonists or immune checkpoint blockadetherapies, including anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4),anti-programmed cell death protein 1 (PD1), and anti-programmed death ligand 1 (PDL1) therapeutic antibodies, radio-immunoconjugates, ADCs, immune/cytokines andmonoclonal antibodies) or treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate,thalidomide, and anti-tumor necrosis factor agents) within 4 weeks or fivehalf-lives of the drug, whichever is shorter, prior to C1D1, or anticipation of needfor systemic immunosuppressive medication during study treatment, with certainexceptions

• Prior treatment with CAR-T-cell therapy within 100 days prior to C1D1; primaryrefractory patients (progressive or persistent disease within 30 days) to CAR-T-celltherapy are not eligible

• Toxicities from prior anti-cancer therapy including immunotherapy that did notresolve to ≤ Grade 1 with the exception of alopecia, endocrinopathy managed withreplacement therapy and stable vitiligo

• Any history of immune-related Grade ≥3 AE with the exception of endocrinopathymanaged with replacement therapy

• Ongoing corticosteroid use greater than 25 mg/day of prednisone or equivalent within 4 weeks prior and during study treatment

• Administration of a live attenuated vaccine within 4 weeks prior to the first doseof study treatment or anticipation that such a live attenuated vaccine will berequired during the study or within 5 months after last dose of study treatment

• Arm E only: Known history of hypersensitivity to obinutuzumab