Using toripalimab and actinomycin-D to treat gestational trophoblastic neoplasia

Efficacy and Safety of Toripalimab Plus Actinomycin-D As Fist-Line Treatment in Patients with Gestational Trophoblastic Neoplasia with FIGO Score 7: a Single-Arm, Multicenter, Phase II Trial

This study is testing if a new combination of toripalimab and actinomycin-D can effectively treat gestational trophoblastic neoplasia in patients with a specific score, to see if it works better than standard chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 17 (estimated)
• Ages: 18 Years to 60 Years
• Sex: Female
• Sponsor: Peking Union Medical College Hospital (Academic / other)
• Drugs / interventions: toripalimab, chimeric antigen receptor, chemotherapy, immunotherapy, prednisone
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06020755 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of toripalimab combined with actinomycin-D as a first-line treatment for patients diagnosed with gestational trophoblastic neoplasia (GTN) who have a FIGO score of 7. Participants will receive intravenous toripalimab and actinomycin-D, with treatment continuing until disease progression, unacceptable toxicity, or withdrawal of consent. The primary goal is to determine the complete remission rate, while secondary objectives include assessing overall survival and quality of life. The study aims to provide insights into the effectiveness of this combination therapy compared to traditional multi-drug chemotherapy.

Who should consider this trial

Good fit: Ideal candidates are women aged 18-60 years diagnosed with GTN and a FIGO score of 7, who have not received prior immunotherapy, chemotherapy, or radiotherapy.

Not a fit: Patients with a FIGO score lower than 7 or those who have previously undergone immunotherapy, chemotherapy, or radiotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the response rates and outcomes for patients with high-risk gestational trophoblastic neoplasia.

How similar studies have performed: While there have been studies on individual components like toripalimab and actinomycin-D, this specific combination for GTN treatment is novel and has not been extensively tested.

Eligibility criteria

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 or longer (days 1, 7, 14, 21). There is a rise (\>10%) in β-hCG for three consecutive weekly 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 4 weeks after abortion, ectopic pregnancy, or term delivery. Pregnancy residue or new pregnancy 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 days before 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 epithelioid trophoblastic 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 is shorter.
7. Previous treatment with immunotherapy drugs (including antibodies targeting PD-1, PD-L1, PD-L2, cytotoxic T-lymphocyte-associated protein 4, T-cell receptor, chimeric antigen receptor T-cell therapy, and other immunotherapy).
8. Known hypersensitivity or allergy to actinomycin-D, toripalimab or any of their excipients.
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 immunosuppressants within 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 controlled arrhythmia (females with QTc interval ≥470 ms); grade III to IV cardiac insufficiency according to New York Heart Association (NYHA) criteria, or cardiac color 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 pericardial disease, or electrocardiogram suggesting acute ischemia or abnormal active conduction system occurring within 6 months before enrolment.
16. Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥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 bleeding tendency or undergoing thrombolysis or anticoagulant therapy.
18. History of cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, 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 organs within 6 months.
20. A history of allogeneic stem cell transplantation or organ transplantation.
21. Other reasons as judged by the investigator.

Where this trial is running

Beijing, Beijing Municipality

• Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Yang Xiang

Conditions Gestational Trophoblastic Neoplasia; International Federation of Gynecology and Obstetrics; Toripalimab; Actinomycin-D; Efficacy; Safety