A Study of RC48-ADC for the Treatment of HER2-expressing Gynecological Malignancies

Inclusion Criteria:

• 1. Meet all the conditions of any of the following queues:
• Queue one:

1. Histologically confirmed patients with recurrent or metastatic cervical cancerwho have failed at least the first-line platinum-containing standard treatment orfailed concurrent radiotherapy and chemotherapy;
2. Not suitable for surgery or radiotherapy.

• Queue two:

1. Ovarian epithelial cancer, fallopian tube cancer or primary peritoneal cancerconfirmed histologically;
2. The subject has previously received a standard platinum-containing chemotherapyregimen, and at the same time meets any of the following criteria: Platinum-resistant relapsed patients who have undergone at least 2 lines (can contain BRCAmutations or HRD-positive patients who have failed PARP inhibitors) standard treatmentfailure (relapse or progression time and previous platinum-containing regimen lastchemotherapy (at least 4 cycles) The interval between time is less than 6 months); or atleast three lines (patients who have failed PARP inhibitors on BRCA mutations orHRD-positive patients) platinum-sensitive relapsed patients who have failed standardtreatment (the time to relapse or progression is related to The interval between the lastplatinum-containing chemotherapy (at least 4 cycles) is ≥ 6 months); Note: The definitionof recurrence or progression (meet any of the following conditions): a) There is clearlyrecorded imaging progress; b) CA-125 continues to rise (CA-125 ≥ 2 times the upper limit ofnormal, and it needs to be confirmed after 1 week ) With clinical symptoms or physicalexamination suggesting disease progression;

• Queue three:

1. Recurrent or metastatic endometrial cancer confirmed histologically;
2. Patients who have failed the standard treatment of at least first-lineplatinum-containing chemotherapy;
3. Not suitable for surgery or radiotherapy.

• Queue four:

1. Recurrent or metastatic other gynecological malignancies (vulvar cancer, vaginalcancer, primary sarcoma of the gynecological reproductive system, etc.) that havefailed standard treatments confirmed by histology;
2. Not suitable for surgery or radiotherapy.

• 2.Voluntarily agree to participate in the research and sign an informed consent form;
• 3. Female, age ≥18 years old;
• 4. Expected survival period ≥ 12 weeks;
• 5.The central laboratory confirms the expression of HER2: IHC 1+, 2+ or 3+; thesubject can provide specimens of the primary or metastatic tumor site for HER2detection (paraffin blocks, paraffin-embedded sections or fresh tissue sections areacceptable); IHC2+ Of subjects need to be tested for FISH. Note: The scoring standardfor HER2 testing is determined by the central laboratory.
• 6. With measurable lesions specified by RECIST 1.1 standard;
• 7. ECOG physical status 0 or 1 point;
• 8. Sufficient organ functions should meet the following criteria during the screeningperiod (the normal value is subject to the clinical trial center): Left ventricularejection fraction ≥50%; Hemoglobin ≥9g/dL; Absolute neutrophil count (ANC)≥1.5×109/L;Platelets ≥100 ×109/L; Serum total bilirubin ≤ 1.5 times the upper limit of normal (ULN); ALT and AST≤2.5 × ULN when there is no liver metastasis, and ALT and AST≤5 ×ULN when there is liver metastasis; Serum creatinine≤1.5×ULN or calculate creatinineclearance rate (CrCl)≥50 mL/min according to Cockcroft-Gault formula method;
• 9 .Female subjects should be surgically sterilized, post-menopausal patients, or agreeto use at least one medically approved contraceptive method (such as intrauterinecontraceptive devices, contraceptives, or condom).The blood pregnancy test must benegative within 7 days before study entry, and it must be a non-lactating period.
• 10. Willing and able to follow the trial and follow-up procedures.

Exclusion Criteria:

• 1.Suffering from central nervous system metastasis and/or cancerous meningitis.Subjects who have received brain metastasis therapy may consider participating in thisstudy, provided that the condition is stable for at least 3 months, no diseaseprogression has been confirmed by imaging examination within 4 weeks before the firstdose of the study, and all neurological symptoms have recovered At baseline, there isno evidence of new or enlarged brain metastases, and radiation, surgery, or steroidtherapy should be discontinued at least 28 days before the first dose of studytreatment. This exception does not include cancerous meningitis, which should beexcluded regardless of whether the clinical condition is stable or not;
• 2. The toxicity caused by previous anti-tumor treatments has not been restored toCTCAE (version 5.0) 0-1 grade (except for 2nd degree alopecia);
• 3. Major surgery has been performed within 4 weeks before the start of studyadministration and has not fully recovered;
• 4. A large amount of pleural fluid or ascites accompanied by clinical symptoms orrequiring symptomatic treatment;
• 5.Serum virology examination (subject to the normal value of the research center): TheHBsAg test result is positive, and the HBV DNA copy number is positive at the sametime; HCVAb test result is positive (only if the PCR test result of HCV RNA isnegative, it can be selected for this study); HIVAb test result is positive.
• 6. Have received live vaccines within 4 weeks before the start of the studyadministration or plan to receive any vaccines during the study period (except the newcrown vaccination);
• 7. Heart failure classified by the New York College of Cardiology (NYHA) as grade 3and above;
• 8. Severe arterial/venous thrombotic events or cardiovascular and cerebrovascularaccidents occurred within 1 year before the study administration, such as deep veinthrombosis (not including asymptomatic intermuscular vein thrombosis without specialtreatment), pulmonary embolism, cerebral infarction, Cerebral hemorrhage, myocardialinfarction, etc., except for lacunar infarction that is asymptomatic and does notrequire clinical intervention;
• 9. There are active or advanced infections that require systemic treatment, such asactive tuberculosis;
• 10.There are systemic diseases that have not been stably controlled by researchers,including diabetes, hypertension, liver cirrhosis, interstitial pneumonia, obstructivepulmonary disease, etc.;
• 11. There are active autoimmune diseases requiring systemic treatment (such asimmunomodulatory drugs, corticosteroids or immunosuppressive agents) within 2 yearsbefore the start of study administration, and related alternative treatments (such asthyroxine, insulin, or renal or Physiological corticosteroid replacement therapy forpituitary insufficiency);
• 12. Suffered from other malignant tumors within 5 years before the start of studyadministration, except for the following conditions: Malignant tumors that can beexpected to heal after treatment (including but not limited to fully treated thyroidcancer, cervical carcinoma in situ, basal or squamous cell skin cancer, or ductalcarcinoma in situ treated by radical surgery);
• 13. Have previously received allogeneic hematopoietic stem cell transplantation;
• 14. Have received other antibody-conjugated drug therapy in the past;
• 15. Those who are known to be allergic to recombinant humanized anti-HER2 monoclonalantibody-MMAE coupling agent drugs and their components;
• 16. Suffer from any other diseases, metabolic abnormalities, abnormal physicalexaminations or abnormal laboratory examinations. According to the judgment of theinvestigator, there is reason to suspect that the patient has a certain disease orcondition that is not suitable for the use of the study drug, or will affect theinterpretation of the study results , Or put the patient in a high-risk situation;
• 17. It is estimated that the compliance of patients to participate in this clinicalstudy is insufficient.