SHR-1701 plus focused stereotactic radiation for metastatic castration‑resistant prostate cancer

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

This study will test whether adding the immune drug SHR‑1701 to focused stereotactic body radiotherapy (SBRT) can help men with metastatic castration‑resistant prostate cancer who have progressed after next‑generation hormone therapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years to 80 Years
• Sex: Male
• Sponsor: Fudan University (other)
• Drugs / interventions: Chemotherapy, Immunotherapy, Radiation, prednisone
• Locations: 3 sites (Fujian and 2 other locations)
• Trial ID: NCT07451795 on ClinicalTrials.gov

What this trial studies

This phase 2 interventional trial combines SHR‑1701, an immune‑modulating agent, with stereotactic body radiotherapy (SBRT) in patients with metastatic castration‑resistant prostate cancer (mCRPC). Eligible participants have confirmed prostate adenocarcinoma, progression after at least one next‑generation hormone therapy, and prior docetaxel exposure or documented intolerance/refusal. Patients will be treated at participating centers with the combination (SHR‑1701 + SBRT) or SBRT alone, with pre‑treatment biopsies encouraged and monitoring by PSA and imaging (RECIST v1.1 and bone scans). The study is led by Fudan University across multiple sites in China to measure anti‑tumor activity and safety of the combination approach.

Who should consider this trial

Good fit: Ideal candidates are men aged 18–80 with histologically confirmed metastatic prostate adenocarcinoma who have progressed after at least one next‑generation hormone therapy, have prior docetaxel exposure (or documented intolerance/refusal), and can undergo SBRT and pre‑treatment biopsy when possible.

Not a fit: Patients with non‑adenocarcinoma prostate cancers, active uncontrolled autoimmune disease, very poor performance status, or who cannot receive SBRT or SHR‑1701 are unlikely to benefit.

Why it matters

Potential benefit: If successful, the combination could improve tumor control and delay the need for more toxic systemic therapies in men with mCRPC.

How similar studies have performed: Combining immune‑modulating drugs with SBRT has shown mixed but sometimes promising signals in other cancers, while single‑agent immunotherapy in mCRPC has generally produced limited benefit except in select molecular subgroups.

Eligibility criteria

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.

Where this trial is running

Fujian and 2 other locations

• Fujian Cancer Hospital — Fujian, China (RECRUITING)
• Fudan University Shanghai Cancer Center — Shanghai, China (RECRUITING)
• Fudan University Shanghai Cancer Center Xiamen Branch — Xiamen, China (RECRUITING)

Study contacts

• Study coordinator: Yao Zhu

Conditions: Prostate Cancer, mCRPC