SHR-1701 in Combination With Stereotactic Body Radiotherapy in mCRPC (SHARP)

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; mCRPC (Metastatic Castration-resistant Prostate Cancer)
• Intervention / Treatment: Combination product: SHR-1701 + SBRT; Radiation: SBRT

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yao Zhu; Phone Number: 13816751347; Email: zhuyao@fudan.edu.cn
• Study Contact Backup: Name: XuDong Ni; Phone Number: 19946234803; Email: xdni18@fudan.edu.cn

Study Locations

• China
  • Fujian, China
    • Recruiting
    • Fujian Cancer Hospital
    • Principal Investigator: Yao Zhu
    • Contact: Yao Zhu; Phone Number: 13816751347; Email: zhuyao@fudan.edu.cn
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Principal Investigator: Yao Zhu
    • Contact: Yao Zhu; Phone Number: 13816751347; Email: zhuyao@fudan.edu.cn
  • Xiamen, China
    • Recruiting
    • Fudan University Shanghai Cancer Center Xiamen Branch
    • Principal Investigator: Yao Zhu
    • Contact: Yao Zhu; Phone Number: 13816751347; Email: zhuyao@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiotherapy plus immunotherapy group; Stereotactic body radiotherapy on targeted metastasis determined by MDT + SHR1701 30mg/kg IV every 3 weeks (Q3W) for 2 cycles, then SHR1701 alone Q3W until progression	Combination product: SHR-1701 + SBRT; Stereotactic body radiotherapy on targeted metastasis determined by MDT + SHR1701 30mg/kg IV every 3 weeks (Q3W) for 2 cycles, then SHR1701 alone Q3W until progression
Active Comparator: Radiotherapy alone group; Stereotactic body radiotherapy on targeted metastasis determined by MDT	Radiation: SBRT; Stereotactic body radiotherapy on targeted metastasis determined by MDT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic Progression-Free Survival (rPFS)	Description: Defined as bone disease progression (occurrence of two or more new lesions on bone scan) per PCWG3, or soft tissue/clinical progression per RECIST v1.1.	From randomization to radiographic progression or death (up to 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR), as assessed by RECIST v1.1 and PCWG3 criteria.	From randomization until progression (up to 24 months)
PSA Response Rate	The proportion of patients achieving a ≥ 50% reduction in serum PSA from baseline, confirmed by a second measurement at least 3 weeks later.	From randomization until progression (up to 24 months)
PSA Progression-Free Survival (PSA-PFS)	Defined according to PCWG3 criteria as: (1) For patients with a decline from baseline: A ≥ 25% increase in PSA and an absolute increase of ≥ 2 ng/mL above the nadir, confirmed by a second measurement at least 3 weeks later; (2) For patients without a decline from baseline: A ≥ 25% increase in PSA and an absolute increase of ≥ 2 ng/mL from baseline after at least 12 weeks of intervention. Subjects with PSA progression alone in the absence of symptomatic or radiographic progression may continue treatment at the investigator's discretion if clinical benefit is perceived.	From randomization until progression (up to 24 months)
Overall Survival (OS)	Defined as the time from enrollment to death from any cause.	From randomization until death (up to 24 months)
Safety and Tolerability	The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.	up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Microenvironment Analysis	Evaluation of the immune microenvironment in peripheral blood and tumor lesions	up to 24 months

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 24, 2025
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 5, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery; SHR-1701
• Other Study ID Numbers: 2509328-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No