Epithelial ovarian cancer
Conditions
Interventions
Queue 1:SHR-A1811 (3.2mg/kg)+Bevacizumab
Queue 2:SHR-A1811 (4.0mg/kg)+Bevacizumab
Expansion stage:SHR-A1811+Bevacizumab
Sponsors
Tongji Hospital, Tongji Medical College ,Huazhong University of Science and Technology
Eligibility
Sex/Gender
Female
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily join this study, sign the informed consent form, have good compliance, and can cooperate with follow-up. 2. Female, aged 18-75 years old (including 18 and 75 years old, calculated on the day of signing informed consent). 3. Epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer (excluding mucinous cancer) diagnosed by organizational or cytological pathology. 4. Previously received 1-3 lines of platinum based treatment and experienced disease progression or recurrence (platinum sensitive recurrence) for >= 6 months (183 days) after the last platinum based treatment; -There must be evidence of platinum based treatment at the end of the line, as well as imaging or clinical progression during or after treatment (such as cytological reports of newly developed ascites or pleural effusion). Elevated CA-125 alone cannot be used as evidence of disease progression or recurrence; -The total of neoadjuvant and/or adjuvant therapy is considered as first-line treatment; Maintenance treatment does not calculate the number of lines separately; The treatment plan changed due to non disease progression reasons (such as toxicity intolerance) is considered as part of first-line treatment and is not separately calculated. 5. Those with a documented mutation (embryonic line or somatic cell) of breast cancer susceptibility gene (BRCA 1/2) or HRD positive must be treated with PARP inhibitors in the past. 6. Capable of providing sufficient fresh or archived tumor tissue specimens for the third-party central laboratory designated by the sponsor to test HER2 expression levels. 7. At least one measurable lesion that meets RECIST v1.1 requirements (according to RECIST v1.1, the length of the measurable lesion on spiral CT scan should be >= 10 mm or the length of enlarged lymph nodes should be >= 15 mm); If there is clear evidence that the lesion has significantly progressed after local treatment, it can be selected as the target lesion. 8. ECOG PS score: 0 to 1. 9. Expected survival period >= 12 weeks. 10. The function of important organs meets the following requirements (no blood components or cell growth factor correction therapy has been used within 14 days before the examination): a) Absolute neutrophil count (ANC) >= 1.5 × 10^9/L; b) Platelet count (PLT) >= 100 × 10^9/L; c) Hemoglobin (Hb) >= 90 g/L; d) Serum albumin (ALB) >= 30 g/L; e) Total bilirubin = 50 mL/min (calculated according to the Cockcroft Gault formula); j) QTc= 50%, and cardiac function test results must be completed within 28 days before the first medication; l) Urinary protein= 2+, the 24-hour urine protein quantification must show<1g of protein. 11. Female subjects with fertility must have a negative serum HCG test within 7 days before the first medication and must be non lactating; Female participants with fertility must agree to comply with contraception requirements from the signing of the informed consent form until the last administration of the investigational drug for a period of 7 months.
Exclusion criteria
Exclusion criteria: 1. Accompanied by untreated or active central nervous system (CNS) tumor metastasis. Subjects with a history of meningeal metastasis or current meningeal metastasis. If the subject's CNS tumor metastasis has received sufficient local treatment (surgery or radiotherapy) and does not require hormone therapy, and has recovered to baseline neurology (except for residual signs or symptoms related to CNS treatment), and has been stable for >= 4 weeks, they can be enrolled. 2. Previously or simultaneously with other malignant tumors, except for cured skin basal cell carcinoma, cervical carcinoma in situ, breast ductal carcinoma in situ, papillary thyroid carcinoma, and other malignant tumors that have been fully treated and cured for >= 3 years with evidence of no recurrence or metastasis. 3. Accompanied by clinical symptoms, uncontrolled, or moderate to severe pleural, pericardial, or peritoneal effusion; If fluid drainage is performed (excluding diagnostic puncture surgery), patients who have been stable for at least 2 weeks after drainage can be enrolled (prior to signing the informed consent agreement, local treatment within the serosal cavity can be given according to the diagnosis and treatment routine). 4. Interstitial pneumonia/interstitial lung disease, non infectious pneumonia (such as radiation pneumonitis) that previously required steroid treatment;Currently present or suspected of having interstitial pneumonia/interstitial lung disease, non infectious pneumonia, or other active pneumonia; Severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, and other lung damage occurred within 6 months before the first medication. 5. Individuals with active pulmonary tuberculosis; Individuals who have received formal and sufficient treatment before their first medication and have stopped anti tuberculosis treatment for at least 3 months are eligible for enrollment. 6. Suffering from hypertension and unable to achieve good control with antihypertensive medication (systolic blood pressure >= 140 mmHg or diastolic blood pressure >= 90 mmHg, based on the average of blood pressure readings obtained from >= 2 measurements, allowing for the use of antihypertensive therapy to achieve the above parameters); Previously experienced hypertensive crisis or hypertensive encephalopathy. 7. Accompanied by poorly controlled or severe cardiovascular diseases, such as unstable angina, symptomatic congestive heart failure (NYHA II-IV), myocardial infarction within 6 months prior to first use, or unstable angina or arrhythmia within 1 month prior to first use. 8. An arterial/venous thrombosis event, including but not limited to cerebrovascular accidents, deep vein thrombosis, and pulmonary embolism, occurred within 6 months prior to the first use of medication; If there is intermuscular vein thrombosis or infusion port catheter related thrombosis before the first medication, and the researcher determines that there is no risk, it can be included. 9. Within one month prior to the first medication, there have been NCI-CTCAE v5.0 grade >= 2 bleeding events, including but not limited to hemoptysis (single episode hemoptysis volume >= 2mL), vaginal bleeding, and gastrointestinal bleeding; Or there may be radiation enteritis accompanied by bleeding symptoms during the screening period; If the baseline occult blood retest is positive and the researcher determines that there is a risk of bleeding, they cannot be included in t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR) (efficacy expansion stage);Dose limiting toxicity (DLT);Recommended Phase II Dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| response rate (RR), CA-125 response rate;Overall survival;Laboratory indicators, 12 lead electrocardiogram, ECOG score, physical examination, vital signs, adverse events (NCI-CTCAE v5.0), etc;PK and immunogenicity of SHR-A1811;Study drug-related adverse events; | — |
Countries
China
Contacts
Public ContactQinglei Gao
Tongji Hospital, Tongji Medical College ,Huazhong University of Science and Technology
Outcome results
None listed