Study of DP303c Injection in Patients With Advanced Ovarian Cancer
Study of DP303c Injection in Patients With Advanced Ovarian Cancer
This study is an open-label, multicentre, phase II study to evaluate the efficacy and safety
 of of DP303c injection in patients with HER2-expressing advanced ovarian cancer.
This is an open-label, multicenter, phase II study of DP303c injection in patients with
 HER2-expressing advanced ovarian cancer with two parts. In part 1, patients will be treated
 with DP303c injection at two dose levels (2.0 mg/kg or 3.0 mg/kg) every 3 weeks to determine
 the recommended phase 2 dose (RP2D). Once the RP2D has been established in part 1, patients
 will be enrolled into 2 cohorts in part 2.
Inclusion Criteria:

 1. Voluntary agreement to provide written informed consent.

 2. Aged 18 to 75 years, female.

 3. Histologically or cytologically confirmed epithelial ovarian cancer, carcinoma tubae,
 or primary peritoneal carcinoma.

 4. Patients have previously received platinum-containing chemotherapy.

 5. Patients must provide tissue samples that are certified as qualified by the central
 laboratory, and the HER2 status of the tissue samples is determined by the central
 laboratory:Part1: HER2 overexpressing: IHC 2+ or IHC 3+; Part2a: HER2 overexpressing:
 IHC 2+ or IHC 3+; Part2b: HER2 low expressing: IHC1+;

 6. The Eastern Cooperative Oncology Group (ECOG) score is 0 to 2, and life expectancy ≥ 3
 months.

 7. At least one measurable lesion at baseline per RECIST v1.1.

 8. The function of major organs must meet the following criteria within 7 days before
 enrollment (Have not received blood transfusion, EPO, G-CSF or other medical
 supportive treatment within 14 days before the first dose of study drug):

 Absolute neutrophil count (ANC) ≥1.5×109/L, Platelet ≥100×109 /L; Hemoglobin ≥90 g/L
 or ≥5.6 mmol/L; International normalized ratio (INR) or prothrombin time (PT)
 ≤1.5×ULN; Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN; Creatinine clearance
 rate ≥30 mL/min (Calculated by Cockcroft-Gualt formula); Total bilirubin ≤1.5×ULN or
 ≤3×ULN for patients with Gilbert's syndrome or liver metastasis: Aspartate
 aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5×ULN or ≤5×ULN for
 patients with liver metastasis:

 9. Female patient of childbearing age must agree to take adequate contraceptive measures
 during the entire study period and through at least 6 months after the last dose of
 study drug. Women of childbearing age must have a negative pregnancy test within 7
 days before study entry.

 10. Patients will be able to communicate well with the investigator, understand and comply
 with the requirements of the study.

 Exclusion Criteria:

 1. Pregnant or breastfeeding women.

 2. Has not recovered from adverse reactions caused by previous anti-tumor treatments to ≤
 grade 1 or baseline (refer to NCI CTCAE 5.0), except for alopecia, pigmentation and
 other toxicity judged no safety risk by the investigator .

 3. Patients who have previously received trastuzumab or trastuzumab analogues that have
 related toxicity, resulting in permanent discontinuation.

 4. Patients with allergic history or delayed allergic reaction to any components
 (trastuzumab analogues, MMAE, sodium citrate dihydrate, citrate monohydrate,
 polysorbate 20 and sucrose, etc.) of DP303c.

 5. Patients with brain or pia mater metastasis, except for patients with central nervous
 system (CNS) metastases in the following conditions: untreated but asymptomatic, or
 progression-free status in imaging evidence for at least 4 weeks after treatment and
 not requiring hormone therapy for at least 4 weeks.

 6. Chemotherapy, radiotherapy, biotherapy, targeted therapy, immunotherapy and other
 anti-tumor treatments within 4 weeks before the first dose of study drug, 6 weeks for
 nitrosourea (such as carmustine, lomustine, etc.) or mitomycin C, 5 half-lives for
 oral fluorouracil and small molecule targeted drugs, 2 weeks for endocrine therapy and
 Chinese medicine treatment with anti-tumor indications; or local palliative
 radiotherapy for bone metastasis and pain relief within 2 weeks.

 7. People who currently have corneal diseases that require medication or surgical
 intervention, or have a history of serious corneal diseases, or are unwilling to stop
 wearing contact lenses during the study.

 8. History of any other malignant tumors within five years (except for skin basal cell
 carcinoma, skin squamous cell carcinoma, superficial bladder cancer, local prostate
 cancer, cervical cancer in situ, stage I ductal carcinoma in situ and stage I grade 1
 endometrial carcinoma that have been radically removed and have not recurred; breast
 cancer with no recurrence for more than 3 years after radical operation).

 9. History of (non-infectious) interstitial lung disease (ILD)/pulmonary disease that
 required steroids, or current ILD/pulmonary disease, or suspected ILD/ pulmonary
 disease that cannot be excluded by imaging examination; except for patients with
 radiation pneumonitis without clinical symptoms after 3 months of radiotherapy.

 10. Patients with dyspnea at rest induced by complications of advanced malignant tumors or
 need for continuous oxygen therapy.

 11. Patients with complete intestinal obstruction, or pleural effusions or ascites that
 are difficult to control within 4 weeks before entry (the frequency of percutaneous
 drainage is more than twice a week, or continuous drainage daily volume is ≥ 1000 mL).

 12. Patients with serious cardiovascular and cerebrovascular diseases, including but not
 limited to:

 -  Uncontrolled angina, congestive heart failure (NYHA III-IV), myocardial
 infarction or severe arrhythmia within 6 months before enrollment;

 -  Left ventricular ejection fraction (LVEF) <50% or lower limit of normal in
 echocardiogram (ECHO) or multi-gate detection scan (MUGA);

 -  Average adjusted QT interval prolongation >470 ms, QT interval corrected by
 Fridericia's formula (QTcF).

 13. The cumulative amount of previous exposure to anthracyclines has reached the following
 doses: doxorubicin or liposomal doxorubicin>500 mg/m2; epirubicin>900 mg/m2;
 mitoxantrone>120 mg/m2; Others (liposomal doxorubicin or other anthracyclines is
 equivalent to a dose of > 500 mg/m2 adriamycin); if more than one anthracycline is
 used, the cumulative dose is equivalent to a total dose of >500 mg/m2 adriamycin.

 14. Peripheral neuropathy ≥grade 2 before entry (NCI CTCAE 5.0).

 15. Uncontrollable electrolyte imbalances include hypokalemia, hypocalcemia or
 hypomagnesemia (refer to NCI CTCAE 5.0, ≥2 grade).

 16. HIV positive, or syphilis infection requiring systematic treatment.

 17. Patients with active hepatitis B or C (HBsAg positive, with HBV DNA positive, and the
 ALT continues to be higher than the upper limit of normal, without other causes of ALT
 elevation; HCVAb positive with HCV RNA higher than the upper limit of normal).

 18. Patients have used strong CYP3A4 inhibitors or CYP3A4 strong inducers with a washout
 period less than 28 days or 5 half-lives (whichever is shorter) before the first dose
 of the study drug.

 19. Patients underwent major surgery within 4 weeks and did not fully recover before the
 first dose of study drug.

 20. Patients have received other clinical trial drugs within 4 weeks before the first dose
 of study drug.

 21. Have previously received antibody drug conjugate targeting HER2.

 22. Patients with any mental or cognitive impairment that may restrict their understanding
 and implementation of the informed consent form.

 23. Other serious or uncontrollable diseases or conditions that may affect the evaluation
 of the primary endpoint or the investigator believes that participation in this study
 may bring risks to the patient.