Platform Study for the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma (PRISM Study)

This is a Phase 1 platform protocol designed to evaluate various targeted agents for the
treatment of relapsed/refractory aggressive Non-Hodgkin's lymphoma (NHL).

Each study arm will be conducted in a predefined disease subset. All study arms are open
label and allocation to each study arm will not be randomized. As this master platform
protocol has multiple study arms, subjects can be screened for several study arms at once.
Likewise, a subject who ends participation in one study arm may be rescreened for
participation in another (separate) study arm. The primary objective of the study is to
evaluate the safety of targeted agents for the treatment of relapsed/refractory aggressive
Non-Hodgkin's Lymphoma (NHL).

This protocol has a modular design, with the potential for future treatment arms to be added
via protocol amendment.

Inclusion Criteria:

Inclusion Criteria For All Arms:

1. Diagnosis of relapsed/refractory aggressive Non Hodgkin's Lymphoma (NHL) with
histology based on established World Health Organization (WHO) criteria.

2. Must have received ≥1 prior line of therapy for the treatment of current histology,
there are no known curative treatment options available, or subject ineligible for
potential curative options.

3. Presence of radiographically measurable lymphadenopathy or extranodal lymphoid
malignancy.

4. ECOG performance status of ≤2.

Inclusion Criteria for Arm 1:

1. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride
(hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with
stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue
and/or chimeric antigen receptor (CAR) T cell therapy.

Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be
determined by the investigator.

Inclusion Criteria for Arm 2:

1. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride
(hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with
stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue
and/or chimeric antigen receptor (CAR) T-cell therapy.

Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be
determined by the investigator.

Exclusion Criteria:

Exclusion Criteria For All Arms:

1. History of prior malignancy except for the following: a) Malignancy treated with
curative intent and with no evidence of active disease present for more than 2 years
before screening and felt to be at low risk for recurrence by treating physician, b)
Adequately treated lentigo maligna melanoma without current evidence of disease or
adequately controlled nonmelanomatous skin cancer, c) Adequately treated carcinoma in
situ without current evidence of disease, d) Evidence of severe or uncontrolled
systemic disease, or current unstable or uncompensated respiratory or cardiac
conditions, or uncontrolled hypertension, history of, or active, bleeding diatheses or
uncontrolled active systemic fungal, bacterial, viral, or other infection, or
intravenous anti-infective treatment within 2 weeks before first dose of study
treatment.

2. Serologic status reflecting active hepatitis B or C infection.

3. Prior use of standard antilymphoma therapy or radiation therapy within 14 days of
receiving the first dose of study treatment (not including palliative radiotherapy or
palliative corticosteroid use).

4. Requires ongoing immunosuppressive therapy, including systemic corticosteroids for
treatment of lymphoid cancer or other conditions.

5. For subjects under DLT review only: Any haematopoietic growth factors or darbepoetin
within 14 days of the first dose of study treatment.

Exclusion Criteria for Arm 1:

1. Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.

2. Current refractory nausea and vomiting, malabsorption syndrome, disease significantly
affecting gastrointestinal (GI) function, resection of the stomach, extensive small
bowel resection that is likely to affect absorption, symptomatic inflammatory bowel
disease, partial or complete bowel obstruction, or gastric restrictions and bariatric
surgery, such as gastric bypass.

3. Requires treatment with proton-pump inhibitors.

4. Requires treatment with strong CYP3A inhibitors or inducers.

Exclusion Criteria for Arm 2:

1. Relative hypotension (< 90/60 mm Hg) or clinically relevant orthostatic hypotension,
including a fall in blood pressure of >20 mm Hg.

2. Uncontrolled hypertension requiring clinical intervention.

3. At risk for brain perfusion problems based on medical history.

4. Mean resting QT interval (QTc) calculated using Fridericia's formula (QTcF) >470 msec
for female subjects and >450 msec for male subjects obtained from 3 electrocardiograms
(ECGs), or congenital long QT syndrome.

5. Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.

6. Known to have tested positive for human immunodeficiency virus (HIV) & requires
treatment with restricted medications.

7. Current refractory nausea and vomiting, malabsorption syndrome, disease significantly
affecting gastrointestinal (GI) function, resection of the stomach, extensive small
bowel resection that is likely to affect absorption, symptomatic inflammatory bowel
disease, partial or complete bowel obstruction, or gastric restrictions and bariatric
surgery, such as gastric bypass.

8. Requires treatment with proton-pump inhibitors.