The purpose of this study is to assess the efficacy of a PARP inhibitor, Pamiparib, in metastatic castration-resistant prostate cancer patients with homologous recombination deficiency or BRCA 1 or 2 somatic/germline mutation.

This is a single arm, open-label, single center, phase II trial, assessing the efficacy of a PARP inhibitor, Pamiparib, in 50 progressing metastatic castration-resistant prostate cancer patients with at least one line of androgen deprivation therapy or chemotherapy at the metastatic setting, and homologous recombination deficiency or BRCA 1 or 2 somatic or germline mutation.

Inclusion Criteria:

1. ≥18 years old, male

2. Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma without neuroendocrine differentiation of the prostate. Mixed histology is accepted, except for small cell carcinoma.

3. Have a deleterious mutation in BRCA1/2 , or HRD score ≥ 9.

4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

5. BPI<4

6. Metastatic Castration-resistant Prostate Cancer (mCRPC): Presence of measurable target lesion according to RECIST criteria v1.1

7. Male subject has been surgically or medically sterilized and has serum testosterone level ≤1.73nmol/L.

8. Unsterilized male subject uses an acceptable method of contraception (defined as a barrier method with spermicide) to prevent pregnancy during the duration of the study and for 6 months after the last dose of Pamiparib.

9. Experienced disease progression after having received at least 1 prior next-generation androgen receptor-targeted therapies, for metastatic castration-resistant disease.

10. Capable of swallowing the whole capsule.

11. Subjects must have normal organ and bone marrow function at baseline, as defined below:

    Hemoglobin ≥ 9.0 g/dL at least 28 days after transfusion . Absolute neutrophil count ≥ 1.5 × 10^9/L. Platelet count ≥ 100 × 10^9/L. Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) specified. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase) ≤ 3 × the specified ULN, unless liver metastases are present, in which case it must be ≤ 5 × ULN.

12. Agree to sign informed consent form

13. Agree not to participate in other interventional trials during this trial.

Exclusion Criteria:

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

1. Acute toxicity (CTCAE > grade 2) due to prior cancer therapy.
2. Received chemotherapy, endocrine therapy, biotherapy, radionuclide therapy, immunotherapy, experimental drugs, proprietary anticancer drugs or Chinese herbal medicines within 5 (if known) half-lives or 14 days(if unknown) prior to the first day of taking Pamiparib; For bisphosphonates or approved bone targeting therapy, Pamiparib must be administered at a steady dose for ≥28 days prior to the first day of taking Pamiparib.
3. Received radiation therapy within 21 days.
4. Prior treatment with any PARP inhibitor. Prior chemotherapy with mitoxantrone or platinum-based chemotherapy or cyclophosphamide. Prior treatment with sipuleucel-T or immune check point inhibitors are allowed.
5. Subjects with major surgery within 2 weeks before starting study treatment. Subjects expected to receive major surgery during the trial.
6. Active second malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer
7. Symptomatic and/or untreated central nervous system metastases
8. Immunocompromised subjects, such as those with positive human immunodeficiency virus (HIV) serology.
9. Subjects with known active hepatitis (e.g. hepatitis B or C).
10. The subject has a serious cardiovascular disease. ( For example, but not limited to: uncontrolled arrhythmia, myocardial infarction)
11. Concomitant use of strong CYP3A inducers or moderate CYP3A inducers . If half-lives is known, a 5 half-lives washout period is required before the start of Pamiparib therapy and a 2-week washout period is required when the half-lives is unknown.
12. History of intolerance to Pamiparib capsule excipients
13. Excluded by investigators