Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study)

This is a prospective, multicenter, randomized, open-label, phase 3 trial evaluating the
efficacy and safety of olaparib versus enzalutamide or abiraterone in subjects with
metastatic castration-resistant prostate cancer (mCRPC) who have failed prior treatment with
a new hormonal agent (NHA) and have a qualifying tumor mutation in one of 15 genes involved
in the homologous recombination repair (HRR) pathway. Subjects will be divided into two
cohorts based on HRR gene mutation status.

Approximately 340 subjects will be randomized 2:1 (olaparib : investigator choice of
enzalutamide or abiraterone acetate) into the trial.

Inclusion criteria

1. Histologically confirmed diagnosis of prostate cancer.

2. Documented evidence of metastatic castration resistant prostate cancer (mCRPC).

3. Subjects must have progressed on prior new hormonal agent (e.g. abiraterone acetate
and/or enzalutamide) for the treatment of metastatic prostate cancer and/or CRPC .

4. Ongoing therapy with LHRH analog or bilateral orchiectomy.

5. Radiographic progression at study entry while on androgen deprivation therapy (or
after bilateral orchiectomy).

6. Qualifying HRR mutation in tumor tissue.

Exclusion criteria

1. Any previous treatment with PARP inhibitor, including olaparib.

2. Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy,
except if for non-prostate cancer indication and last dose > 5 years prior to
randomization.

3. Other malignancy (including MDS and MGUS) within the last 5 years except: adequately
treated non-melanoma skin cancer or other solid tumors curatively treated with no
evidence of disease for ≥5 years.

4. Subjects with known brain metastases.