SHR-1701 in Combination With Stereotactic Body Radiotherapy in mCRPC

A Prospective, Randomized, Controlled Phase II Study of SHR-1701 in Combination With Stereotactic Body Radiotherapy (SBRT) for Metastatic Castration-Resistant Prostate Cancer

The aim of this study is to evaluate the efficacy of SHR-1701 in combination with SBRT in patients with metastatic castration-resistant prostate cancer. Dr. Yao Zhu from Fudan University Shanghai Cancer Center is the co-leading PI of this study.

Inclusion Criteria:

1. Age: 18 to 80 years old.

2. Diagnosis: Histologically or cytologically confirmed adenocarcinoma of the prostate, clinically staged as metastatic prostate cancer based on conventional imaging (bone scan or CT/MRI).

3. Biopsy: Whenever possible, patients should undergo a pre-treatment image-guided biopsy of a lesion; alternatively, archived biopsy tissue obtained within 30 days prior to enrollment is acceptable.

4. Prior Therapy: Failure of at least one prior next-generation hormone therapy (NHT), such as abiraterone acetate, rezivilutamide, enzalutamide, apalutamide, or darolutamide.

5. Chemotherapy History: Prior treatment with docetaxel, or documentation of intolerance to or refusal of chemotherapy.

6. Disease Progression: Evidence of disease progression defined by: PSA progression: At least two consecutive increases in PSA levels, measured at least 1 week apart, with a screening PSA value ≥ 1 ng/mL; OR Radiographic progression in soft tissue per RECIST v1.1 (with or without PSA progression); OR Bone progression per PCWG3 criteria (occurrence of ≥ 2 new bone lesions on bone scan).

7. Castration Status: Maintenance of effective and continuous luteinizing hormone-releasing hormone analog (LHRHa) therapy throughout the study period, or prior bilateral orchidectomy; serum testosterone must be maintained at castrate levels (< 50 ng/dL).

8. Performance Status: ECOG Performance Status score of 0 to 2.

9. Life Expectancy: ≥ 6 months.

10. Hematologic Function: Absolute neutrophil count (ANC) ≥ 1.5 ×10^9/L; Platelets ≥ 75 ×10^9/L; Hemoglobin ≥ 90 g/L; White blood cell (WBC) count ≥ 3.0 ×10^9/L.

11. Hepatic Function (Transaminases): Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN); for patients with liver metastases, ALT/AST ≤ 5 × ULN.

12. Hepatic Function (Bilirubin): Total bilirubin ≤ 1.5 × ULN, or total bilirubin > 1.5

    × ULN if direct bilirubin ≤ ULN.

13. Coagulation Function: INR ≤ 1.5, Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, and Prothrombin time (PT) < ULN + 4 seconds.

14. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 50%; QTc < 450 ms for males; serum potassium ≥ 3.5 mmol/L.

15. Blood Pressure: Systolic BP < 160 mmHg and diastolic BP < 95 mmHg; patients with stable BP after appropriate clinical management are eligible.

16. Renal Function: Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min.

17. Contraception: Sexually active patients with ejaculatory potential must agree to use effective contraception and refrain from sperm donation from the first dose until 3 months after the last dose of study treatment.

18. Informed Consent: Ability to understand and willingness to sign a written Informed Consent Form (ICF).

19. Compliance: Ability to comply with the study visit schedule and other protocol requirements.

Exclusion Criteria:

1. Concurrent Therapy: Plan to receive any other anti-tumor therapy during the study treatment period.
2. Brain Metastasis: Presence of brain metastases.
3. Prior Immunotherapy: Previous treatment with immune checkpoint inhibitors (including PD-1, PD-L1, CTLA-4 inhibitors, etc.) or any anti-tumor agents targeting T-cells or activating the immune system.
4. Other Malignancies: Known other malignancies that are progressing or require active treatment within the past 3 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy.
5. Autoimmune Disease/Infection: Active autoimmune disease or active infection (including tuberculosis) requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within the past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement for adrenal/pituitary insufficiency) is not considered systemic treatment.
6. Immunosuppression: Diagnosis of immunodeficiency or receipt of chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose.
7. Pneumonitis: History of (non-infectious) pneumonitis requiring steroid treatment or current non-infectious pneumonitis.
8. Prior Radiation/Hormonal Washout: Receipt of radiotherapy or radionuclide therapy (e.g., Radium-223) within 28 days prior to the first dose; or abiraterone within 1 week, or other anti-androgen therapy within 2 weeks prior to the first dose.
9. Hypersensitivity: Hypersensitivity or intolerance to the active ingredients or any excipients of the PD-L1 monoclonal antibody.
10. Neuropsychiatric Disorders: Known history of significant neurological or psychiatric disorders, such as dementia, epilepsy, or seizure-prone conditions.
11. Concomitant Conditions: Any concurrent medical condition (e.g., severe diabetes, thyroid disease, or psychiatric illness) that, in the investigator's judgment, poses a severe risk to subject safety or interferes with study completion; or any unstable medical/psychiatric condition (including laboratory abnormalities) that compromises safety or the ability to provide informed consent; or any psychological, familial, social, or geographical conditions that may affect protocol compliance and follow-up.
12. Investigator's Discretion: Any other reason that the investigator deems the patient unsuitable for participation in this clinical trial.