This study is an open-label Phase II randomized controlled trial designed to evaluate the safety and efficacy of camrelizumab plus fluzoparib maintenance therapy in patients with recurrent or metastatic TP-53 mutated Endometrial Cancer. The study will also explore the prevalence of homologous recombination reficiency in Chinese patients with TP-53 mutated endometrial cancer and its therapeutic significance.
The treatment of recurrent or metastatic endometrial carcinoma (R/M-EC) has entered the era of molecular marker oriented precision therapy. Meanwhile, several large multicenter Phase III RCT studies have been conducted, such as NRG-GY018, RUBY, DUO-E and AtTEnd, and suggested that chemotherapy combined with immunotherapy could significantly improve the prognosis of R/M-EC. Unfortunately, the efficacy of ICBs in Asian R/M-EC population is not obvious, with small size. On the other hand, up to 63% of patients with R/M-EC have TP-53 gene mutations (TP53mut). And the efficacy of chemotherapy combined with immunotherapy in thse patients is controversial. In the RUBY study, TC combined with Dostarlimab reduced the risk of death in patients with TP53mut-R/M-EC by 59 percent. However, in the DUO-E study, chemotherapy combined with Durvalumab failed to improve serous -EC in 154 patients (approximately 92% TP53mut). Therefore, how to optimize the strategy of chemotherapy combined with immunotherapy in TP53mut-R/M-EC is urgently needed. Considering TP53mut-EC patients with tumor local T-lymph Cell infiltration and PD-L1 expression were significantly higher than those of TP-53 gene wild type (TP53wt) patients. It was also suggested that ICB and PARPi had a good synergistic effect. The DUO-E study revealed the combination of Durvalumab and Olaparib maintenance therapy significantly improves the prognosis of serous EC. Therefore, as an investigator-initiated open-label Phase II randomized controlled study, the study will include 117 patients with TP53mut-R/M-EC, and randomly divided 2:1 into experimental group and control group to evaluate the safety and efficacy of camrelizumab plus fluzoparib maintenance therapy in patients with recurrent or metastatic TP-53 mutated Endometrial Cancer. The study will also explore the prevalence of homologous recombination reficiency in Chinese patients with TP-53 mutated endometrial cancer and its therapeutic significance.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
117
During the maintenance phase of treatment. Oral administration of Fluzoparib capsules at a dose of 150mg(N=78 participants), once in the morning and once in the evening until disease progression, intolerable toxicity, death, or up to a maximum of 2 years.
During the maintenance phase of treatment. Camrelizumab, 200 mg administered intravenously every 3 weeks until disease progression, intolerable toxicity, death, or up to 2 years.
Paclitaxel (albumin-bound) for injection, 260 mg/m\^2 administered intravenously in 3-week cycles for 6 cycles.
AUC=5 Intravenous dosing is administered every 3 weeks for a total of 6 treatment cycles. Specific dosing cycles may be determined by the investigator
AUC=5 Intravenous dosing is administered every 3 weeks for a total of 6 treatment cycles. Specific dosing cycles may be determined by the investigator
Non-essential, decision to combine is made by the principal investigator based on the patient's condition.
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
RECRUITINGInvestigator-assessed progression-free survival (PFS)
The time between randomization and tumor progression or death
Time frame: 12 months
Duration of Response(DoR)
The duration of remission or complete disappearance of the patient's disease after treatment
Time frame: 12 months
Overall Survival(OS)
The time between randomization and death.
Time frame: 24 months
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