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

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.

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.

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;