B-Cell Lymphoma Clinical Trials

• Individuals with any of the following large B-cell lymphomas, as determined by the investigator, are eligible for the study as defined below:

‣ World Health Organization (WHO):

• Individuals with chemorefractory disease to first-line therapy (primary refractory disease) that satisfies any of the following criteria:

‣ Progressive disease (PD) and/or Deauville score of 5 (irrespective of the response designation) as the best response during the first-line treatment or as the end of treatment response following first-line therapy.

⁃ Stable disease (SD) after at least 4 cycles of first-line therapy (eg, 4 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)).

⁃ PR as best response after at least 6 cycles of first-line therapy (eg, 6 cycles of R-CHOP).

⁃ Note: A biopsy is recommended to confirm residual disease.

∙ Individuals with relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven disease relapsed ≤ 12 months of completion of first-line therapy.

∙ Note: If the relapse is confirmed by imaging per International Working Group (IWG) Lugano Response Criteria for Malignant Lymphoma within 12 months, the confirmatory biopsy must be performed within 90 days of the 12-month cutoff.

∙ Prior therapy must have included an anti-CD20 antibody (including CD20-targeting T-cell engager antibodies) and an anthracycline-containing chemotherapy regimen.

∙ For individuals with transformed indolent NHL, therapies given for non-transformed disease do not count as a line of therapy for the transformed disease.

∙ Individuals who have had no additional systemic therapy or holding therapy (except for steroids and/or local radiation) following first-line therapy and prior to leukapheresis are eligible.

• At least 1 measurable lesion according to the IWG Lugano Response Criteria. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. A measurable lesion is defined as \>1.5 cm longest transverse diameter (LDi) for lymph node and \> 1.0 cm LDi for extranodal lesion. Splenomegaly or hepatomegaly alone in the absence of a measurable lesion is not considered to be measurable disease.

• The following washout period must be satisfied:

‣ At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the individual is randomized.

• Toxicities due to immediate prior therapy must have recovered to Grade 1 or lower (except for clinically nonsignificant toxicities such as alopecia, unless otherwise specified in the protocol)

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

• Adequate bone marrow function as evidenced by:

‣ Absolute neutrophil count ≥ 1,000/μL or ≥ 500/μL if documented bone marrow involvement of lymphoma. Bone marrow involvement by lymphoma is demonstrated by positron emission tomography (PET) scan or bone marrow aspiration or bone marrow biopsy.

⁃ Platelet count ≥ 75,000/μL (unless secondary to bone marrow or spleen involvement by lymphoma, in which platelet count ≥ 50,000 μL is permitted). Bone marrow involvement by lymphoma is demonstrated by PET scan or bone marrow aspiration or bone marrow biopsy. Spleen involvement by lymphoma is demonstrated by PET-diagnostic computed tomography (CT) involvement, splenomegaly, or biopsy.

• Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:

‣ Creatine clearance (as estimated by Cockcroft-Gault formula) ≥ 30 mL/minute. Note: 24-hour urine estimate is also acceptable.

⁃ Serum alanine aminotransferase/aspartate aminotransferase ≤ 3.0 times the upper limits of normal, except in individuals with documented liver involvement by lymphoma via PET-diagnostic CT scan or biopsy

⁃ Total bilirubin ≤ 1.5 mg/dL, except in individuals with Gilbert's Syndrome or documented liver or pancreatic involvement where ≤ 3.0 times the upper limit of normal is permitted

⁃ Cardiac ejection fraction ≥ 40% and no pericardial effusion Grade 3 or higher (per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0) as determined by an echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) (if ECHO not available at the site). Note: If there is any concern for pericardial effusion, an ECHO must be performed since MUGA alone is not an adequate modality to assess for pericardial effusion.

⁃ No evidence of Grade 2 (per CTCAE v5.0) or greater pleural effusion or ascites (individuals with Grade 1 ascites or pleural effusion are eligible)

⁃ Baseline oxygen saturation \> 92% on room air

• Females of childbearing potential must have a medically supervised negative serum or urine pregnancy test (females who have undergone surgical sterilization or have been postmenopausal for at least 2 years before randomization are not considered to be of childbearing potential.