Safety and Efficacy of AEB071 and EVEROLIMUS in Patients With CD79-mutant or ABC Subtype Diffuse Large B-Cell Lymphoma

This is a Phase Ib dose escalation and Phase II study in patients with DLBCL harboring
mutations in CD79A/B or of the ABC subtype. Pre-screening for mutations in CD79A/B or the
ABC subtype will be required, as it is anticipated that both patient groups may receive
clinical benefit from the combination of AEB071 and EVEROLIMUS.

Inclusion Criteria:

- Male or female ≥18 years of age.

- Diffuse DLBCL with activating mutations in CD79 (A or B subunits) or ABC-subtype
DLBCL (CD79 wildtype or CD79 mutant). DLBCL that arose from transformed indolent
lymphoma is allowed.

- Prior treatment and relapse following chemotherapy and autologous bone marrow or stem
cell transplant. Patients who are not transplant eligible or who did not respond to
chemotherapy may be considered for the study following a single regimen of
chemotherapy such as R-CHOP or R-EPOCH. There is no limit to number of prior
therapies allowed.

- May be treated with localized radiation as long as measurable or evaluable disease
remains at untreated sites.

- WHO performance status of ≤ 2.

- A representative FFPE tumor sample must be available for molecular testing along with
a corresponding pathology report. An archival tumor sample may be submitted. However,
if not available, a new tumor biopsy obtained for the purpose of this study must be
submitted instead.

Exclusion Criteria:

- Treatment with strong inducers or inhibitors (medications and herbal supplements) of
cytochrome P450 3A4/5 (CYP3A4/5), or CYP3A4/5 substrates with a QT prolongation risk
that cannot be discontinued at least 7 half-lives (or if the half-life is unknown,14
days) prior to study drug treatment.

- Impaired cardiac function or clinically significant cardiac diseases.

- Impairment of GI function or GI disease that could interfere with the absorption of
AEB071 or everolimus.

- Severe systemic infections, current or within the two weeks prior to initiation of
AEB071.

- Kown history of HIV.

- Poorly controlled diabetes as defined by a fasting serum glucose > 2.0 x ULN.

- Evidence of current CNS involvement.

- Significant symptomatic deterioration of lung function.