Prostate Cancer (Adenocarcinoma), Prostate Cancer Metastatic Castration-Resistant, Prostate Adenocarcinoma With Neuroendocrine Differentiation
Conditions
Keywords
NEPC, AVPC, TROP2, PD-L1
Brief summary
This study is a prospective, single arm II clinical trial. The main objective of the study is to evaluate the efficacy and safety of the combination of Sacituzumab Tirumotecan (SKB264) and Tagitanlimab (KL-A167) in the treatment of AVPC (aggressive variant prostate cancer) and NEPC (neuroendocrine prostate cancer).
Detailed description
More than 60% of newly diagnosed cases of prostate cancer in China are in the middle and late stages, with an overall poor prognosis. Prostate cancer is AVPC (aggressive variant prostate cancer) and NEPC (neuroendocrine prostate cancer), two highly invasive and poorly prognosis non androgen receptor driven subtypes of prostate cancer. The overall prognosis of advanced AVPC and NEPC is poor, with a median OS of only 7-20 months after diagnosis. At present, there is a lack of a unified standard protocol for drug treatment of AVPC and NEPC. The recommended treatment plan in the diagnosis and treatment guidelines is mainly platinum based chemotherapy, as the behavior of AVPC and NEPC is similar to that of small cell lung cancer, and can be treated according to the guidelines for small cell lung cancer.More research is still underway on the use of immunotherapy combined with chemotherapy for advanced AVPC/NEPC. This study is a prospective, single arm II clinical trial. The main objective of the study is to evaluate the efficacy and safety of the combination of Sacituzumab Tirumotecan (SKB264) and Tagitanlimab (KL-A167) in the treatment of advanced AVPC and NEPC.The above research suggests that immunotherapy combined with chemotherapy has further exploration value in advanced AVPC/NEPC.
Interventions
DRUGSacituzumab Tirumotecan
Drug reduction will be implemented according to the research plan.
DRUGTagitanlimab
Treatment with Sacituzumab Tirumotecan (SKB264, 5mg/kg IV d1 Q2W) and Tagitanlimab (KL-A167 , 900mg IV d1 Q2W) until confirmed by the investigator as imaging disease progression, intolerable toxicity, subject's request to terminate treatment, or other treatment termination criteria specified in the protocol (based on the first patient), with a maximum treatment duration of 24 months for Tagitanlimab. Drug reduction will be implemented according to the research plan.
Sponsors
Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
Tianjin Medical University Second Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age at the time of signing the informed consent form is ≥ 18 years old; 2. AVPC or NEPC diagnosed based on recent histological and/or clinical criteria; 3. Having received one or two second-generation anti androgen therapies in the past, previous use of docetaxel for castration resistant prostate cancer (CRPC) is allowed, and the use of other chemotherapy is not allowed; 4. The progression of prostate cancer in the subjects within 6 months prior to screening shall be determined by the researcher through one of the following methods: PSA is evaluated by local laboratories, and PSA progression is defined as at least two increases in PSA levels at intervals of ≥ 1 week, with a screening PSA value of ≥ 2 ng/ml. • Soft tissue imaging disease progression determined based on PCWG modified RECIST 1.1 or RECIST 1.1 criteria, regardless of PSA progression. The imaging disease progression of bones is defined as the appearance of two or more new bone lesions in bone scans, regardless of PSA progression. 5. Subjects who have not undergone past surgery must be using and voluntarily continue to use luteinizing hormone releasing hormone (LHRH) agonists throughout the entire study treatment period; 6. According to RECIST v1.1, there should be at least one measurable lesion, and previously irradiated lesions should not be selected as target lesions; Subjects with only skin or bone lesions are not eligible for inclusion; 7. Within 7 days prior to administration, the physical fitness status score of the Eastern Cooperative Oncology Group (ECOG) in the United States was 0 or 1; 8. Expected survival period ≥ 12 weeks; 9. Having sufficient organ and bone marrow function (without receiving blood transfusion, recombinant human thrombopoietin or colony-stimulating factor therapy within 2 weeks prior to administration), defined as follows: 1. Blood routine: neutrophil count (NEUT #) ≥ 1.5 × 109/L; platelet count (PLT) ≥ 100 × 109/L; hemoglobin ≥ 90 g/L; 2. Liver function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; For subjects with liver metastasis at baseline, ALT and AST should be ≤ 5 × ULN; Albumin ≥ 30g/L; Total bilirubin (TBIL) ≤ 1.5 × ULN; 3. Renal function: creatinine clearance rate ≥ 50 ml/min (calculated using the standard Cockcroft Gault formula); 4. Coagulation function: International normalized ratio (INR), activated partial thromboplastin time (APTT), and prothrombin time (PT) ≤ 1.5 × ULN; 10. For subjects whose partners have fertility potential, they must agree to take effective medical contraceptive measures within 6 months from the signing of the informed consent form until the last administration (see Annex 2 for details); 11. The subjects voluntarily joined this study, signed an informed consent form, and were able to comply with the visit and related procedures specified in the protocol.
Exclusion criteria
1. Previously received any of the following treatments (including in the context of adjuvant or neoadjuvant therapy): 1. Targeted treatment of TROP2; 2. Any drug therapy containing targeted topoisomerase I, including antibody conjugated drug (ADC) therapy; 3. Immune checkpoint inhibitors (such as anti-PD-1/L1 antibodies, anti-CTLA-4 antibodies, etc.), immune checkpoint agonists (such as ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immune cell therapy, and any other treatment targeting the tumor immune mechanism; 2. Those who require the use of strong inhibitors or inducers of cytochrome P450 3A4 enzyme (CYP3A4) within 2 weeks prior to the first administration and during the study period (strong inhibitors or inducers of CYP3A4 are not allowed in this study, and representative drugs of CYP3A4 strong inhibitors or inducers are listed in Appendix 7); All subjects must avoid the concurrent use of any drugs, herbal supplements, and/or intake of such foods known to induce CYP3A4 as much as possible; 3. Subjects with central nervous system (CNS) metastases known to have meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, active or untreated conditions. For subjects with brain metastases who have received local treatment in the past, if they have been clinically stable for at least 4 weeks before medication and have not required the use of glucocorticoids or anticonvulsants for at least 14 days, they are allowed to be enrolled; 4. Suffering from other malignant tumors within 3 years before administration (excluding tumors that have been cured through local treatment, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, cervical carcinoma in situ, etc.); 5. There are any of the following cardiovascular diseases or cardiovascular risk factors: 1. Within 6 months prior to administration, if there is a myocardial infarction, unstable angina, acute or persistent myocardial ischemia, grade 3 or 4 heart failure (according to the New York Heart Association (NYHA) classification), symptomatic or poorly controlled severe arrhythmia, cerebrovascular accident, transient ischemic attack, or other serious cardiovascular and cerebrovascular diseases; 2. Previous history of myocardial diseases such as myocarditis, primary cardiomyopathy, and specific cardiomyopathy; 3. Any deep vein thrombosis (if stabilized for ≥ 2 weeks with low molecular weight heparin or similar efficacy drugs), peripheral arterial thromboembolic events, pulmonary embolism, or other serious thromboembolic events within 3 months prior to administration; 4. Major vascular diseases that may endanger life or require surgery within 6 months prior to administration, such as aortic aneurysm, aortic dissection aneurysm, etc; 6. According to researchers' assessment, uncontrolled systemic diseases: 1. Poor control of diabetes (fasting blood glucose ≥ 10 mmol/L for two consecutive times); 2. Poor control of hypertension (systolic blood pressure\>160 mmHg and/or diastolic blood pressure\>100 mmHg); 3. Presence of pleural effusion, pericardial effusion, or ascites with clinical symptoms or requiring repeated drainage (\>once per week); 7. History of (non infectious) interstitial lung disease (ILD) or non infectious pneumonia requiring steroid treatment, current ILD or non infectious pneumonia, or suspected ILD or non infectious pneumonia that cannot be excluded by imaging examination during screening; 8. Clinical severe lung damage caused by concurrent lung diseases, including but not limited to any underlying lung disease (such as pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc. within 3 months before administration) or any autoimmune, connective tissue, or inflammatory disease that may affect the lungs (i.e. rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or previous total pneumonectomy; 9. Subjects with active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcers, gastrointestinal perforation, abdominal abscess, or acute gastrointestinal bleeding; 10. Individuals with bleeding tendencies such as acute gastrointestinal bleeding, persistent bleeding disorders, or coagulation dysfunction; 11. The toxicity of previous anti-tumor treatments has not yet recovered to ≤ level 1 (evaluated based on NCI CTCAE v5.0) or the levels specified in the inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 24 months | Objective Response Rate (ORR) assessed according to the evaluation criteria for the efficacy of solid tumors (RECIST v1.1)/ Prostate Cancer Clinical Trials Working Group(PCWG3). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival(PFS) | From treatment administration up to a maximum duration of 24 months. | The time from the beginning of the patient's treatment to the disease progression or death for any reason. Based on RECIST criteria v1.1/ PCWG3. |
| Duration of Response(DOR) | Through study completion, an expected average of 24 months. | Duration of Response, from the first time the evaluation results meet CR or PR criteria to the observation of PD or death. |
| Percentage of Participants With Adverse Events (AEs) | Up to approximately 24 months. | Number of participants with adverse effects of treatment. Frequency and severity of adverse effects of treatment as assessed by NCI CTCAE v5.0. |
| Disease Control Rate (DCR) | From treatment administration up to a maximum duration of 24 months. | The proportion of subjects with complete response (CR) and partial response (PR) and stable disease (SD) in total subjects after the last subject participating in. |
| Overall Survival(OS) | From treatment administration up to a maximum duration of 24 months. | Time from start of treatment to death due to any cause. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploring predictive effectiveness indicator | Up to approximately 24 months. | Explore potential biomarkers for predicting therapeutic efficacy, including but not limited to immune related indicators such as PD-L1, TILs, lymphocyte subsets, and TROP2 expression. |
Countries
China
Contacts
Primary ContactHaitao Wang, Ph.D
Backup ContactJinhuan Wang, Ph.D
Outcome results
None listed