The purpose of this study is to evaluate the efficacy and safety of camrelizumab and apatinib as combination therapy in patients with ultra high-risk (Cohort A) and high-risk chemo-refractory or relapsed (Cohort B) gestational trophoblastic neoplasia (GTN). Eligible patients will receive camrelizumab plus apatinib plus chemotherapy. Treatment will be continued until disease progression, unacceptable toxicity, or withdrawal of consent.
Woman aged 18-60 years;
Previously untreated patients with ultra high-risk GTN（Cohort A） or high-risk chemo-refractory or relapsed GTN (Cohort B);
No previous chemotherapy or radiotherapy for ultra high-risk GTN（Cohort A）and have previously received two or more lines of combination chemotherapies for high-risk chemo-refractory or relapsed GTN (Cohort B);
Patients with ultra high-risk GTN (FIGO stages I-III: score ≥13 and stage IV) according to the International Federation of Gynecology and Obstetrics (FIGO) 2000 staging and risk factor scoring system（Cohort A）and patients with a prognostic score ≥7 (Cohort B);
Previous treatment with immunotherapy drugs (including antibodies targeting PD-1, PD-L1, cytotoxic T-lymphocyte-associated protein 4, T-cell receptor, chimeric antigen receptor T-cell therapy, and other immunotherapy), anti-angiogenic small-molecule tyrosine kinase inhibitors (such as pazopanib, sorafenib, or regorafenib), or anti-angiogenic monoclonal antibodies (such as bevacizumab); live vaccines injected within 4 weeks before the first dose of study drug; other clinical trials of antitumour drugs within 4 weeks before the first dose of study drug;
Other malignancies in the past 3 years;
Immunosuppressive drugs used within 14 days prior to the first dose of camrelizumab; any active autoimmune disease or a history of autoimmune disease;
Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, despite with the optimal drug therapy);
Parallel
Camrelizumab plus apatinib CohortA
DrugCamrelizumab (200 mg q2w iv) concomitantly with apatinib (250 mg qd po) and EMA/CO (etoposide, methotrexate, actinomycin D/cyclophosphamide, vincristine, alternate weekly) chemotherapy. For patients with high tumor burden, 1-2 cycles of low-dose chemotherapy will be administered to avoid early death caused by sudden tumor collapse, then followed by standard chemotherapy of EMA/CO. The low-dose chemotherapy will be administered using AE (actinomycin D 500 ug and etoposide 100mg/m2, day 1-3,every 2 week) or EP (etoposide 100 mg/m2 and cisplatin 20 mg/m2, day 1-2, repeated weekly).
Camrelizumab plus apatinib Cohort B
DrugCohort B: Camrelizumab (200 mg q3w iv) concomitantly with apatinib (250 mg qd po) and multi-drug chemotherapy. The multi-drug chemotherapy regimen will be chosen by the investigator (chemotherapy regimen: EMA/CO \[etoposide, methotrexate, actinomycin D/cyclophosphamide, vincristine\]; or EMA/EP \[etoposide, methotrexate and actinomycin-D/etoposide, cisplatin\]; or FAEV \[floxuridine, actinomycin-D, etoposide, vincristine\]). The observation period is 21 days.
Cohort A: Complete remission rate
The proportion of patients achieving complete remission. Complete remission is defined as normal serum β-hCG level measured for 3 consecutive weeks.
Cohort B: Objective response rate
The proportion of patients with complete or partial response according to serum β-hCG level. Partial response is defined as a ≥50% decrease in β-hCG level from baseline after 2 cycles.
Cohort A: Objective response rate
The proportion of patients with complete or partial response according to serum β-hCG level.
Cohort A: Progression-free survival
The time from the treatment initiation to disease progression or death, whichever comes first. Disease progression is defined as any increase in serum β-hCG level from baseline after 2 cycles of treatment or the presence of new metastatic lesions.
Cohort A: Overall survival
The time from the treatment initiation to the date of death or last follow-up.
Cohort A: Duration of response
The time from the first evidence of response to disease progression or death, whichever comes first.
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Peking Union Medical College Hospital
Lead sponsor
Jiangsu HengRui Medicine Co., Ltd.
Collaborator
