Olaparib Tablets as a Treatment for Ovarian Cancer Subjects With Different HRD Tumor Status

This is a Phase II, open-label, non-randomized, multi-center study assessing the efficacy and
safety of olaparib tablets 300 mg (two 150 mg tablets) given orally twice daily (bid) in
subjects with platinum-sensitive or partially platinum-sensitive, relapsed, high-grade serous
or high-grade endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer,
who have received at least 1 prior line of platinum-based chemotherapy.

The study will assess the effectiveness of olaparib tablets as measured by the objective
response rate (ORR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1, in subjects with germline BRCA mutations (gBRCAm), somatic BRCA mutations (sBRCAm), or
potential aberrations in homologous recombination deficiency (HRD) as determined by myChoice®
HRD, as well as in subjects without identifiable HRD. This study will utilize Myriad
BRACAnalysis CDx® for germline BRCA analysis and a tumor test (myChoice® HRD) for tumor BRCA
analysis and HRD status. Four cohorts will be identified based upon the genetic testing
described above:

- Cohort 1: gBRCAm,

- Cohort 2: sBRCAm and germline BRCA wild type,

- Cohort 3: myChoice® HRD positive (genomic instability positive) and BRCA wild type
(BRCAwt) (no BRCA mutation),

- Cohort 4: myChoice® HRD negative (genomic instability negative) and BRCAwt (no BRCA
mutation).

Inclusion Criteria:

- Provision of written signed informed consent prior to any study specific procedures;

- Female subjects with histologically diagnosed relapsed high-grade serous or high-grade
endometrioid ovarian cancer;

- At least 1 lesion (measurable by RECIST v1.1) that can be accurately assessed at
baseline by computed tomography (CT)/magnetic resonance imaging (MRI) and is suitable
for repeated assessment;

- Subjects must have received at least 1 prior platinum-based line of chemotherapy for
ovarian cancer. Note: There is no limit on the number of lines of chemotherapy;

- Subjects must be partially-platinum-sensitive (defined as progression 6 to 12 months
after the end of the last platinum-based chemotherapy) or platinum sensitive (defined
as progression > 12 months after the end of the last platinum-based chemotherapy);

- Subjects must have normal organ and bone marrow function measured within 28 days prior
to administration of study treatment;

- ECOG performance status 0 to 1;

- Subjects must have a life expectancy greater than or equal to 16 weeks;

- Postmenopausal or evidence of non-childbearing status for women of childbearing
potential: negative urine or serum pregnancy test within 28 days of study treatment
and confirmed prior to treatment on Day 1;

- Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations; and

- Formalin fixed, paraffin embedded tumor sample (either archival or fresh sample) from
the primary or recurrent cancer must be available for central testing. If there is not
written confirmation of the availability of an archived or fresh tumor sample prior to
enrollment, the subject is not eligible for the study.

Exclusion Criteria:

- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
Representative staff and/or staff at the study site);

- Previous enrollment in the present study;

- Exposure to any investigational product (IP) within 30 days or 5 half-lives (whichever
is longer) prior to start of study treatment;

- Any previous treatment with a PARP inhibitor, including olaparib;

- Subjects who have platinum-resistant or refractory disease defined as progression
during or within 6 months of the last platinum-based chemotherapy;

- Other malignancy within the last 5 years (few exceptions apply);

- Resting ECG with clinically significant abnormal findings;

- Subjects receiving any systemic chemotherapy or radiotherapy (except for palliative
reasons) within 3 weeks prior to study treatment;

- Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors;

- Concomitant use of known strong or moderate CYP3A inducers;

- Persistent toxicities (> Common Terminology Criteria for Adverse Event [CTCAE] grade
2) caused by previous cancer therapy, excluding alopecia;

- Subjects with MDS/AML or with features suggestive of MDS/AML;

- Subjects with pneumonitis or at risk of pneumonitis;

- Subjects with symptomatic uncontrolled brain metastases;

- Major surgery within 2 weeks of starting study treatment, and subjects must have
recovered from any effects of any major surgery;

- Subjects considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease, or active, uncontrolled infection;

- Breast feeding women;

- Immunocompromised subjects, e.g., subjects who are known to be serologically positive
for human immunodeficiency virus;

- Subjects with known active hepatitis (i.e., Hepatitis B or C) due to risk of
transmitting the infection through blood or other body fluids