Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL

Inclusion Criteria:

• Participants with relapsed or refractory diffuse and transformed large B-celllymphoma (R/R DLBCL). DLBCL and cell of origin (GCB versus non-GCB) will behistologically determined by local pathology assessment for the purposes of studyeligibility and stratification.

• Participants must have R/R disease following 2 or more lines of prior systemictherapy.

• For participants with transformed DLBCL, at least the last systemic therapyused must have been for DLBCL

• Participants must be HSCT or CAR-T ineligible according to the investigator and mustmeet at least one of the following criteria:

1. One or more co-morbidities, including cardiac, pulmonary, renal or hepaticdysfunction that in the opinion of the Investigator make the participantmedically unfit to received HSCT or CAR-T therapy

2. Active disease following induction and salvage chemotherapy

3. Inadequate stem cell mobilization (for HSCT)

4. Relapse following prior HSCT or CAR-T

5. Unable to receive CAR-T therapy due to financial, geographic, insurance, ormanufacturing issues

• Participants must have tumor tissue submitted to the central pathology lab. Thetumor tissue submitted should be from the most recent biopsy that contains DLBCL.

• An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2

• Participants must have fluorodeoxyglucose (FDG)-avid disease by positron emissiontomography (PET) and bidimensional measurable disease of at least 1.5 cm by computedtomography (CT), as assessed by the site radiologist within 28 days of Day 1.

Exclusion Criteria:

• History of another malignancy within 2 years before the first dose of study drug orany evidence of residual disease from a previously diagnosed malignancy

• History of progressive multifocal leukoencephalopathy (PML)

• Active cerebral/meningeal disease related to the underlying malignancy. Participantswith a history of cerebral/meningeal disease related to the underlying malignancyare allowed if prior CNS disease has been effectively treated and withoutprogression for at least 3 months.

• Any uncontrolled Grade 3 or higher (per NCI CTCAE version 5.0) viral, bacterial, orfungal infection within 2 weeks prior to the first dose of study drug. Routineantimicrobial prophylaxis is permitted

• Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment withimmunotherapy that is not completed 3 weeks prior to first dose of study drug,unless underlying disease has progressed on treatment

• Previous treatment with brentuximab vedotin or lenalidomide.

• Previous treatment with other vedotin-based ADCs is permitted if the last doseis at least 6 months prior to Day 1.

• Current therapy with immunosuppressive medications (including steroids), othersystemic anti-neoplastic, or investigational agents a) Prednisone (or equivalent) ≤10 mg/day may be used for non-lymphomatous purposes

• Documented history of a cerebral vascular event (stroke or transient ischemicattack), unstable angina, myocardial infarction, or cardiac symptoms consistent withNew York Heart Association (NYHA) Class III-IV within 6 months prior to the firstdose of study drugs

• Congestive heart failure, Class III or IV, by the NYHA criteria

• Grade 2 or higher peripheral sensory or motor neuropathy at baseline