A Study of Rucaparib in Patients With Pancreatic Cancer and a Known Deleterious BRCA Mutation

Rucaparib is an orally available, small molecule inhibitor of poly-adenosine diphosphate
[ADP] ribose polymerase (PARP) that inhibits a specific DNA repair pathway known as base
excision repair (BER). PARP inhibitors (PARPi) have been shown to effectively kill tumors
with a defect in BRCA1 or BRCA2. Clinical benefit has been observed in patients with a gBRCA
mutation as well as in those with a somatic BRCA (sBRCA) mutation. Clinical data have also
shown that pancreatic cancer patients with a gBRCA mutation benefit from PARPi treatment.
Clinical activity of PARP inhibitors in BRCA-mutated pancreatic cancer combined with the
paucity of 2nd line therapies support evaluation of rucaparib in pancreatic cancer patients
known to harbor a deleterious BRCA mutation.

Inclusion Criteria:

- Confirmed diagnosis of pancreatic cancer (ductal adenocarcinoma and related subtypes
eligible; endocrine and neuroendocrine tumors excluded)

- Received at least 1, but no more than 2, chemotherapy-based regimens for locally
advanced or metastatic disease and has relapsed or progressive disease. Patients no
longer able to continue treatment with chemotherapy due to intolerable toxicity may be
considered for study participation provided that radiology assessment confirms either
stable disease or disease progression (i.e. no response to treatment)

- Documented deleterious or suspected deleterious (or equivalent interpretation) BRCA
mutation (germline or somatic) as assessed by a local laboratory

- Measurable disease

Exclusion Criteria:

- Presence of another active cancer

- Prior treatment with any PARP inhibitor, including rucaparib. Patients treated with
prior iniparib are eligible.

- Symptomatic and/or untreated central nervous system metastases.

- Clinical evidence of malabsorption and/or any other gastrointestinal disorder or
defect that would, in the opinion of the investigator, interfere with the absorption
of rucaparib.