Toripalimab Plus Actinomycin-D As Fist-Line Treatment for GTN with FIGO Score 7

Inclusion Criteria:

1. Diagnosed as GTN: There is a histologic diagnosis of choriocarcinoma or invasive mole. Postmolar GTN:The plateau of β-hCG (±10%) lasts for four measurements over a period of 3 weeks orlonger (days 1, 7, 14, 21). There is a rise (>10%) in β-hCG for three consecutiveweekly measurements over at least a period of 2 weeks or more (days 1, 7, 14). GTN after nonmolar pregnancy: There is a rise after decease, or a plateau of β-hCG 4weeks after abortion, ectopic pregnancy, or term delivery. Pregnancy residue or newpregnancy have been ruled out.

2. Patients with a FIGO score of 7.

3. Signed informed consent.

4. No previous immunotherapy, chemotherapy, or radiotherapy.

5. Woman aged 18-60 years.

6. Expected survival ≥ 6 months.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 7 daysbefore first dose.

8. The function of vital organs meets the following requirements:

hemoglobin ≥90 g/L, absolute neutrophil count ≥1·5×109/L, platelets ≥100×109/L; creatinine ≤1·5 × upper limit of normal (ULN), urea nitrogen ≤2·5×ULN; total bilirubin ≤1.5×ULN, alanine aminotransferase and aspartate aminotransferase ≤2·5×ULN, INR, PT or APTT ≤1.5×ULN, thyroid stimulating hormone ≤ULN (if thyroid stimulating hormone is abnormal, normal T3 and T4 can also be acceptable).

Exclusion Criteria:

1. Histologically confirmed placental-site trophoblastic tumor (PSTT) or epithelioidtrophoblastic tumor (ETT).

2. Histologically confirmed primary choriocarcinoma.

3. Other malignancies in the past 3 years.

4. Prior systemic anti-cancer treatment, including chemotherapy and radiotherapy.

5. Live vaccines injected within 30 days before the first dose of study drug;

6. Systemic immune stimulant agent (such as a bacterial or viral vaccine,colony-stimulating factors, interferon, interleukin, and combined vaccine) was used 6 weeks before administration or within the 5 half-lives of the drug, whichever isshorter.

7. Previous treatment with immunotherapy drugs (including antibodies targeting PD-1,PD-L1, PD-L2, cytotoxic T-lymphocyte-associated protein 4, T-cell receptor, chimericantigen receptor T-cell therapy, and other immunotherapy).

8. Known hypersensitivity or allergy to actinomycin-D, toripalimab or any of theirexcipients.

9. Any active autoimmune disease requiring systemic treatment during the past 2 years.

10. History or current status of non-infectious pneumonia requiring steroid treatment.

11. Receiving steroid hormones (prednisone dose > 10mg/ day) or other immunosuppressantswithin 14 days before enrollment, excluding those on hormone replacement therapy.

12. Active infection that requires systemic treatment.

13. Human immunodeficiency virus infection or known acquired immunodeficiency syndrome,active hepatitis B, hepatitis C.

14. History of psychotropic drug abuse and are unable to withdraw the psychotropic drug,or have mental disorders.

15. Grade II or higher myocardial ischemia, myocardial infarction or poorly controlledarrhythmia (females with QTc interval ≥470 ms); grade III to IV cardiacinsufficiency according to New York Heart Association (NYHA) criteria, or cardiaccolor Doppler ultrasound evidence of left ventricular ejection fraction <50%;myocardial infarction, NYHA grade II or above heart failure, uncontrolled angina,uncontrolled severe ventricular arrhythmia, clinically significant pericardialdisease, or electrocardiogram suggesting acute ischemia or abnormal activeconduction system occurring within 6 months before enrolment.

16. Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic bloodpressure ≥90 mmHg, despite with the optimal drug therapy).

17. Abnormal coagulation (international normalized ratio >1·5×ULN or prothrombin time >ULN+4 seconds or activated partial thromboplastin time >1·5×ULN), with bleedingtendency or undergoing thrombolysis or anticoagulant therapy.

18. History of cerebrovascular accident (including transient ischemic attack, cerebralhemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism within 3 months before enrolment.

19. Obvious factors affecting oral drug absorption, such as inability to swallow,chronic diarrhea and intestinal obstruction, or sinus or perforation of empty organswithin 6 months.

20. A history of allogeneic stem cell transplantation or organ transplantation.

21. Other reasons as judged by the investigator.