Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-cell Lymphoma and Follicular Lymphoma

Study CC-122-DLBCL-001 is a Phase 1b dose escalation and expansion clinical study of CC 122,
CC-223 and CC-292 administered orally as doublets with or without rituximab, in subjects with
relapsed/refractory DLBCL who have failed standard therapy.

In expansion phase, selected combination will be administered to lenalidomide naïve FL
subjects and lenalidomide exposed FL subjects in addition to relapsed/refractory DLBCL
subjects.

Inclusion Criteria:

- Men and women, 18 years or older, with histologically or cytologically-confirmed
either:

1. Chemo-refractory DLBCL (including transformed low grade lymphoma)

2. Lenalidomide naïve; relapsed or refractory CD20-positive follicular lymphoma
(Grade 1, 2, or 3a) following at least one prior standard systemic treatment
regimen including systemic chemo-, immune-; or chemo-immunotherapy and at least
one prior line of salvage therapy with no prior exposure to lenalidomide, or
double-refractory FL subjects with no prior exposure to lenalidomide (FL-1
cohort)

3. Lenalidomide exposed: relapsed or refractory CD20-positive follicular lymphoma
(Grade 1, 2, or 3a) previously treated with at least two cycles of
lenalidomide-containing regimen (FL-2 cohort), either as a single agent or in
combination

- At least one site of measurable disease

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.

- Subjects must have the following laboratory values:

- Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L or ≥ 1.0 x 109/L (with bone marrow
involvement with DLBCL)

- Hemoglobin (Hgb) ≥ 8 g/dL.

- Potassium within normal limits

- Asparate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) and
Alanine Aminotransferase/Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) ≤ 2.5 x Upper
Limit of Normal (ULN) or ≤ 5.0 X ULN if liver tumor is present.

- Serum bilirubin ≤ 1.5 x ULN.

- Estimated serum creatinine clearance of ≥ 50 mL/min

- Subjects must have the following laboratory values:

Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L without growth factor support for 7 days (14
days if subject received pegfilgrastim).

- Males enrolled into treatment arms receiving CC-122 must: Agree to abstain from
donating sperm while taking IP and for at least 3 months following discontinuation of
IP

Exclusion Criteria:

- Symptomatic central nervous system involvement.

- Known symptomatic acute or chronic pancreatitis.

- Persistent diarrhea or malabsorption despite medical management.

- Peripheral neuropathy ≥ grade 2

- Impaired cardiac function or clinically significant cardiac diseases

- Subjects with diabetes on active treatment (for subjects treated on CC-223 containing
arms only)

- Prior autologous stem cell transplant (ASCT) ≤ 3 months before first dose.

- Prior allogeneic stem cell transplant with either standard or reduced intensity
conditioning.

- Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives
or 4 weeks prior to starting study drugs, whichever is shorter.

- Subjects who have undergone major surgery ≤ 2 weeks prior to starting study drugs.

- Women who are pregnant or breast feeding. Adults of reproductive potential not willing
to employ two forms of birth control.

- Subjects with known HIV infection, chronic active hepatitis B or C virus (HBV/HCV)
infection.

- Subjects with treatment-related myelodysplastic syndrome.

- History of concurrent second cancers requiring active, ongoing systemic treatment.

- Prior treatment with a dual mTORC1/mTORC2 inhibitor (CC-223 arms only) or BTK
inhibitor (PCI-32765) (CC-292 arms only). [Prior treatment with rapamycin analogues,
PI3K or AKT inhibitors, lenalidomide and rituximab are allowed].