Locally Advanced Cervical Cancer
Conditions
Keywords
Cervical Cancer, neoadjuvant, chemo-immunotherapy, iparomlimab and tuvonralimab;
Brief summary
Locally advanced cervical cancer (LACC) remains a significant global health concern with limited treatment options. Recent advancements suggest that using neoadjuvant anti-PD-1 inhibitors in combination with chemotherapy, followed by radical surgery, may be an effective treatment strategy for patients with PD-L1-positive LACC. This study aims to evaluate the efficacy and safety of preoperative treatment with iparomlimab and tuvonralimab-a bifunctional PD-1/CTLA-4 dual blocker-combined with chemotherapy for LACC.
Detailed description
A total of 43 patients with FIGO 2018 stages IB3, IIA2, IIB, or IIIC1r will receive a combination treatment consisting of iparomlimab and tuvonralimab (5 mg/kg administered intravenously), cisplatin (75-80 mg/m², intravenously), and nab-paclitaxel (260 mg/m², intravenously) for one cycle. Following this, patients will receive two additional cycles of iparomlimab and tuvonralimab at the same dosage of 5 mg/kg, administered at three-week intervals. After completing three cycles of neoadjuvant treatment, patients who show a complete response (CR) or partial response (PR) will undergo radical surgery. The decision regarding subsequent adjuvant therapy will be guided by the NCCN guidelines. In contrast, patients with stable or progressive disease will proceed to concurrent chemoradiotherapy (CCRT).
Interventions
DRUGneoadjuvant chemo-immunotherapy: Iparomlimab and tuvonralimab plus cisplatin,nab-paclitaxel for 1 cycle and Iparomlimab and tuvonralimab for 2 cycles
Neoadjuvant chemo-immunotherapy: Iparomlimab and tuvonralimab, cisplatin, and nab-paclitaxel for 1 cycle, then Iparomlimab and tuvonralimab continued for 2 cycles at 3-week intervals. Details: Iparomlimab and tuvonralimab 5 mg/kg, IV infusion, Q3W for 3 cycles Cisplatin：75-80 mg/m2, IV infusion, (cycle 1) Nab-paclitaxel 260 mg/m2，30min，IV infusion,(cycle 1)
Sponsors
Jiangsu Cancer Institute & Hospital
Fuzhou University Affiliated Provincial Hospital
First Affiliated Hospital of Fujian Medical University
Fujian Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The iparomlimab and tuvonralimab at a dosage of 5 mg/kg administered intravenously, along with cisplatin (75-80 mg/m², intravenously) and nab-paclitaxel (260 mg/m², intravenously) for one cycle. Then, two additional cycles (interval of 3 weeks) of iparomlimab and tuvonralimab (5 mg/kg, intravenously) were followed.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 1、Written informed consent * 2、18-70 years old * 3、Adequate organ function and ECOG of 0 \ 1 * 4、Without systemic therapy at the time of enrollment * 5、FIGO 2018 stage IB3, IIA2, or IIIC1r * 6、Histologically confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix * 7、Measurable lesions could be defined by RECIST v1.1 * 8、Willing to get blood/ tumor tissue tested * 9、Patients who observed the rules about the scheduled visit, study schedule, and medical examination * 10、The function of major organs is normal, and the following criteria are met: * 10.1 Blood routine examination must meet: (no blood transfusion within 14 days) Hb≥90g/L: ANC≥1.5x10\^9/L; PLT≥100x10\^9/L; * 10.2 The biochemical examination must meet the following standards BIL \< 1.5 × ULN; ALT and AST \< 2.5xULN; ALB≥ 28 g/L * 11、Patients who are willing and able to comply with visiting arrangements, treatment plans, laboratory tests, and other research procedures.
Exclusion criteria
* 1、History of other malignancies within 3 years * 2、Participate in other clinical trials at the same time * 3、Active autoimmune disease, which needs systemic therapy * 4、Uncontrolled infection, which needs systemic therapy * 5、History of allogeneic tissue/solid organ transplant * 6、Serious illness, such as severe mental disorders, cardiac disease, coagulation disorders, digestive system disease, etc * 7、Active HBV, HCV, or HIV infection * 8、Pregnant or lactating female patients * 9、Drug or alcohol abuse * 10、 Unable or unwilling to sign the informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response (pCR) | From enrollment to the end of surgery at 3 months | Pathological complete response（pCR） is defined as the absence of viable tumor cells by surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | From enrollment to the end of surgery at 3 months | ORR is defined as the proportion of patients who achieve either a complete or partial response, as assessed by two experienced medical oncologists according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
| Event-free survival (EFS) | Through the study completion, an average of 2 year | EFS is defined as the time from initial treatment to the date of disease progression that prevents definitive surgery, local or distant recurrence, occurrence of a second primary cancer, or death from any cause, whichever occurs first. |
| Primary pathological response (MPR) | From enrollment to the end of surgery at 3 months | MPR is defined as having no more than 10% viable tumor by surgery. |
| Disease-free survival (DFS) | Through the study completion, an average of 2 year | DFS is the interval from the initial treatment to the first occurrence of locoregional failure, distant metastasis, or death from any cause. |
| Adverse events | During the treatment（12months） | Incidence of Treatment-Emergent Adverse Events, Including adverse events and complications. Incidence of adverse events using CTCAE 5.0; grade 3 treatment-related adverse events and higher-grade will be reported |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry | Samples taken prior/after to every cycle of treatment, or at progression, an average of 2 year | Using flow cytometry to analyze the peripheral blood mononuclear cells to predict the efficacy of neoadjuvant chemo-immunotherapy. Results will be summarized by dose level |
| Tumor micrioenviroment assessment | Samples taken prior/after to every cycle of treatment, or at progression, an average of 2 year | using tumor tissue (multiple immunofluorescence) to assess immune cells before and after 3 cycles of neoadjuvant chemo-immunotherapy |
Countries
China
Contacts
Primary ContactYang Sun, PHD
Backup ContactJie Lin, MD
Outcome results
None listed