Safety and Efficacy Evaluation of Anti IGF-1R Monoclonal Antibody Combined With Anti-PD-1 Monoclonal Antibody in Treatment in Patients With Metastatic Castration-Resistant Prostate Cancer

This trial is designed to evaluate the safety and efficacy of anti-IGF-1R mAb in combination with anti-PD-1 mAb in patients with mCRPC.

Study Overview

• Status: Active, not recruiting
• Conditions: mCRPC
• Intervention / Treatment: Drug: anti-IGF-1R mAb (Teprotumumab/IBI311) + anti-PD-1 mAb (Tislelizumab)

Detailed Description

This trial is designed to primarily confirm the safety and tolerability of anti-IGF-1R mAb (Teprotumumab/IBI311) in combination with anti-PD-1 mAb (Tislelizumab) using the recommended dose level for patients with mCRPC patients. Additionally，this trial is aimed to evaluate the clinical efficacy of anti-IGF-1R mAb combined with anti-PD-1 mAb in the treatment of mCRPC patients and to investigate whether the combined treatment can enhance endocrine therapy sensitivity in mCRPC patients. As for exploratory objectives，the trial is designed to identify and validate predictive biomarkers associated with therapeutic efficacy and safety profiles of the combination regimen in mCRPC patients.

• Study Type: Interventional
• Enrollment (Estimated): 7
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Shanghai Changzheng Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Men over 18 years old and under 85 years old;
2. Diagnosed with prostate adenocarcinoma by prostate biopsy pathology report;
3. Patients with metastatic castration-resistant prostate adenocarcinoma (mCRPC);
4. evidence of metastatic bone lesions on imaging such as PSMA-PET-CT or bone metastasis imaging ECT;
5. Serum testosterone in the depot range (< 50 ng/dL or 1.75 nmol/L);
6. Patients need to be willing to undergo pre- and on-treatment biopsy;
7. ECOG score ≤ 2;
8. Expected survival time of 6 months or more;

9. Substantially normal bone marrow, liver and kidney function:

   1. white blood cell (WBC) > 3 x 10^9 cells/L
   2. Absolute neutrophil count (ANC) > 1×10^9 cells/L
   3. Hemoglobin >9.0 g/dL
   4. Platelet count >100×10^9/L
   5. Serum creatinine <1.5 × upper limit of normal (ULN)
   6. Serum total bilirubin <1.5 × ULN
   7. Serum glutamine aminotransferase <3 × ULN
   8. Aspartate aminotransferase <3 × ULN
10. willingness to cooperate and complete study follow-up and related tests.
11. The subject or his/her representative voluntarily participates in the study and signs a written informed consent; and
12. The questionnaire can be completed in Chinese.
13. The patient has been informed of the trial;

Exclusion Criteria:

1. Histologically predominantly other types of prostate cancer, such as sarcomas, lymphomas, small cell tumors, and neuroendocrine tumors;
2. Active infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5 o F or 38.1 o C) within 1 week prior to enrollment;
3. have received systemic, ongoing immunosuppressive therapy within 14 days prior to receiving study treatment (except for adrenal replacement steroid doses not exceeding 10 mg prednisone equivalent per day in the absence of active autoimmune disease or short-term steroid therapy (<5 days) within 7 days prior to initiation of study treatment);

4. Subjects with severe cardiovascular disease;

   1. New York Heart Association (NYHA) Stage III or IV congestive heart failure;
   2. episode of myocardial infarction or coronary artery bypass grafting (CABG) ≤ 6 months prior to enrollment;
   3. clinically significant ventricular arrhythmia, or history of unexplained syncope, non-vasovagal or not due to dehydration;
   4. history of severe non-ischemic cardiomyopathy;
   5. reduced left ventricular ejection fraction (LVEF <55%), abnormal septal thickness and atrial size associated with myocardial amyloidosis, as assessed by echocardiography or multigated circuit exploration (MUGA) scan;

5. Organ function is in the following abnormalities:

   1. serum aspartate aminotransferase or alanine aminotransferase > 2.5*ULN; CK > *ULN; CK-MB > *ULN; TnT > 1.5*ULN;
   2. Total bilirubin > 1.5*ULN;
   3. partial thromboplastin time or activated partial thromboplastin time or international normalized ratio > 1.5*ULN in the absence of anticoagulant therapy;
6. Patients who have planned or may plan to undergo extracorporeal radiation therapy or surgery for prostate cancer during the study period;
7. Prior anti-IGF-1R monotherapy and any immune checkpoint inhibitor therapy;
8. Intolerance to anti-IGF-1R monotherapy drugs and immune checkpoint inhibitors;
9. uncontrolled major active infectious disease, cardiovascular disease, pulmonary disease, hematologic disease, or psychiatric disease;
10. In the opinion of the investigator, not suitable for participation in this clinical study;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment with anti-IGF-1R mAb(Teprotumumab/IBI311) + anti-PD-1 mAb (Tislelizumab)	Drug: anti-IGF-1R mAb (Teprotumumab/IBI311) + anti-PD-1 mAb (Tislelizumab); Drug: Teprotumumab/IBI311 Given by IV infusion Initiate dosing with 10 mg/kg for first infusion, followed by 20 mg/kg every 3 weeks. Drug: Tislelizumab Given by IV infusion 200 mg every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and adverse event incidence rate	Incidence rate of adverse events graded according to the National Cancer Institute Common Criteria for Adverse Events (NCI CTCAE) version 5.0.	Through primary completion of study which may take up to 6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-month PSA progression-free survival (PSA-PFS)	Time from enrollment to PSA progression as defined by PCWG3 or patient death.	3 months after first infusion
6-month imaging progression-free survival (rPFS):	Time from enrollment to imaging progression or death from any cause, to be evaluated in conjunction with the RECIST 1.1 criteria and the PCWG3 criteria.	6 months after first infusion
6-month PSA progression-free survival (PSA-PFS)	Time from enrollment to PSA progression as defined by PCWG3 or patient death.	6 months after first infusion
PSA Response Rate	Percentage of PSA decline from baseline according to PCWG3 criteria	Through primary completion of study which may take up to 6 months.
Disease Control Rate	Defined as the proportion of patients whose tumors shrunk or remained stable for a certain period of time after treatment, judged according to RECIST 1.1 and PCWG3 to include the proportion of patients with complete remission (CR), partial remission (PR), and stable disease (SD).	Through primary completion of study which may take up to 6 months.
Objective Response Rate	Define the proportion of patients with disease CR or PR as determined by RECIST 1.1 and PCWG3 , after treatment;	Through primary completion of study which may take up to 6 months.
Overall Survival	Defined as the time from randomization grouping to the last available assessment or death;	Through primary completion of study which may take up to 6 months.
Incidence of bone metastasis-related events (SREs)	Incidence of bone radiotherapy (including radioisotopes), pathologic fractures (excluding trauma), spinal cord compression, and bone surgery.	Through primary completion of study which may take up to 6 months.
Quality of life (QoL)	QoL was monitored using the validated and self-rated EORTCQLQ-C30	Through primary completion of study which may take up to 6 months.
Quality of life (QoL) FACT-P questionnaire	QoL was monitored using the validated and self-rated questionnaire	Through primary completion of study which may take up to 6 months.
Time to pain progression	Time from the date of randomization to the date on which the pain severity score (using the BPI-SF) increased by 30% or more from baseline. Or the time from the date of randomization to the date of observation of a 2-point increase from baseline in the BPI-SF worst pain intensity (point 3 on the scale) on 2 consecutive assessments ≥4 weeks apart or initiation of chronic opioid use, whichever occurred first.	Through primary completion of study which may take up to 6 months.

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital
• Investigators: Principal Investigator: Shancheng Ren, MD,PhD, Shanghai Changzheng Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2025
• Primary Completion (Actual): November 11, 2025
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: March 3, 2025
• First Submitted That Met QC Criteria: March 7, 2025
• First Posted (Actual): March 10, 2025

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Prostate Cancer; PD-1; Metastasis; IGF-1R
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Prostatic Neoplasms; Neoplasm Metastasis; Insulin-Like Growth Factor I, Resistance To; Antineoplastic Agents, Immunological; Antineoplastic Agents; teprotumumab; tislelizumab
• Other Study ID Numbers: HELIX-25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified participant data from the final research dataset used in the published manuscript may only be shared under the consent and approval of principal investigator, but this does not mean all requests will be approved.
• IPD Sharing Time Frame: Beginning 6 months and ending 1 year after the publication of results
• IPD Sharing Access Criteria: Information regarding submitting proposals and accessing data maybe requested from the principal investigator by e-mail.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No