A Study of Duvelisib in Combination With Rituximab and Bendamustine vs Placebo in Combination With Rituximab and Bendamustine in Subjects With Previously-Treated Indolent Non-Hodgkin Lymphoma (BRAVURA)

Study IPI-145-22 is an international, multicenter, randomized, double-blind,
placebo-controlled, two-arm Phase 3 study designed to evaluate efficacy and safety of DBR vs
PBR in subjects with previously-treated iNHL (including follicular lymphoma [FL], small
lymphocytic lymphoma [SLL] and marginal zone lymphoma [MZL]).

Approximately 600 subjects will receive 25 mg of duvelisib or placebo, orally BID for 28 day
continuous cycles, in combination with 375 mg/m2 of rituximab given on Day 1 of Cycles 1-6
and 90 mg/m2 of bendamustine given on Day 1 and Day 2 of Cycles 1-6. Subjects will receive
duvelisib until disease progression or unacceptable toxicity.

Inclusion Criteria:

- Diagnosis of iNHL with one of the following histologic sub-types and grade:

- Follicular lymphoma (FL)Grade 1, 2, or 3a

- Small lymphocytic lymphoma (SLL)

- Marginal zone lymphoma (MZL)( splenic, nodal, or extranodal)

- Have received the following systemic treatments for iNHL:

- an anti-CD20 antibody; and

- chemotherapy

- At least 1 measurable disease lesion > 1.5 cm in at least one dimension by computed
tomography (CT)/CT-PET or magnetic resonance imaging (MRI)

- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 (corresponds to
Karnofsky Performance Status [(KPS) ≥60%])

Exclusion Criteria:

- Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade
3B FL

- Refractory to bendamustine + rituximab therapy or single-agent bendamustine 120 mg/m2,
with refractory defined as:

− Progression of disease while receiving or within 6 months of completing treatment

- Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine
protein, or known hypersensitivity to any of the study drugs

- Received prior allogeneic transplant

- Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor

- Infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).

- History of tuberculosis treatment within the two years prior to randomization

- History of chronic liver disease, veno-occlusive disease, or alcohol abuse

- Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic
steroids > 20 mg of prednisone (or equivalent) daily (QD)

- Ongoing treatment for systemic bacterial, fungal, or viral infection at screening

- Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV),
or herpes zoster (VZV) at screening

- Concurrent active malignancy other than adequately treated non-melanoma skin cancer or
lentigo maligna without evidence of invasive disease or adequately treated cervical
carcinoma in situ without evidence of disease

- History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia
requiring medication or a pacemaker within the last 6 months prior to screening

- History of progressive multifocal leukoencephalopathy