Neoadjuvant Iparomlimab and Tuvonralimab Plus Chemotherapy-eclipse for Locally Advanced Cervical Cancer (NICE-CC)

Official title

Neoadjuvant Therapy of Iparomlimab and Tuvonralimab Combined With Chemotherapy-eclipse for Locally Advanced Cervical Cancer：A Single-arm, Open-label, Phase II Trial

Overview

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

• Drug neoadjuvant 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)

Primary outcome measures

• Pathological complete response (pCR) [Time frame: From enrollment to the end of surgery at 3 months]

Secondary outcome measures (5)

• Objective response rate (ORR) [Time frame: From enrollment to the end of surgery at 3 months]
• Event-free survival (EFS) [Time frame: Through the study completion, an average of 2 year]
• Primary pathological response (MPR) [Time frame: From enrollment to the end of surgery at 3 months]
• Disease-free survival (DFS) [Time frame: Through the study completion, an average of 2 year]
• Adverse events [Time frame: During the treatment（12months）]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fujian Cancer Hospital — Fuzhou

Publications

• Wu X, Sun Y, Yang H, Wang J, Lou H, Li D, Wang K, Zhang H, Wu T, Li Y, Wang C, Li G, Wang Y, Li D, Tang Y, Pan M, Cai H, Wang W, Yang B, Qian H, Tian Q, Yao D, Cheng Y, Wei B, Li X, Wang T, Hao M, Wang X, Wang T, Ran J, Zhu H, Zhu L, Liu X, Li Y, Chen L, Li Q, Yan X, Wang F, Cai H, Zhang Y, Liang Z, Liu F, Huang Y, Xia B, Qu P, Zhu G, Chen Y, Song K, Sun M, Chen Z, Zhou Q, Hu L, Abulizi G, Guo H, PMID 39426385
• Nederlof I, Isaeva OI, de Graaf M, Gielen RCAM, Bakker NAM, Rolfes AL, Garner H, Boeckx B, Traets JJH, Mandjes IAM, de Maaker M, van Brussel T, Chelushkin M, Champanhet E, Lopez-Yurda M, van de Vijver K, van den Berg JG, Hofland I, Klioueva N, Mann RM, Loo CE, van Duijnhoven FH, Skinner V, Luykx S, Kerver E, Kalashnikova E, van Dongen MGJ, Sonke GS, Linn SC, Blank CU, de Visser KE, Salgado R, Wess PMID 39284953
• Keam SJ. Iparomlimab and Tuvonralimab: First Approval. Drugs. 2025 May;85(5):699-706. doi: 10.1007/s40265-025-02160-6. Epub 2025 Apr 1. PMID 40167968
• Li K, Chen J, Hu Y, Wang YZ, Shen Y, Chen G, Peng W, Fang Z, Xia B, Chen X, Song K, Wang Y, Zou D, Wang YC, Han Y, Feng X, Yuan J, Guo S, Meng X, Feng C, Chen Y, Yang J, Fan J, Wang J, Ai J, Ma D, Sun C. Neoadjuvant chemotherapy plus camrelizumab for locally advanced cervical cancer (NACI study): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2024 Jan;25(1):76-85. doi: 10.1016/S1470-2045( PMID 38048802
• Miriyala R, Mahantshetty U, Maheshwari A, Gupta S. Neoadjuvant chemotherapy followed by surgery in cervical cancer: past, present and future. Int J Gynecol Cancer. 2022 Mar;32(3):260-265. doi: 10.1136/ijgc-2021-002531. PMID 35256411
• Abu-Rustum NR, Yashar CM, Arend R, Barber E, Bradley K, Brooks R, Campos SM, Chino J, Chon HS, Crispens MA, Damast S, Fisher CM, Frederick P, Gaffney DK, Gaillard S, Giuntoli R, Glaser S, Holmes J, Howitt BE, Lea J, Mantia-Smaldone G, Mariani A, Mutch D, Nagel C, Nekhlyudov L, Podoll M, Rodabaugh K, Salani R, Schorge J, Siedel J, Sisodia R, Soliman P, Ueda S, Urban R, Wyse E, McMillian NR, Aggarwa PMID 38081139
• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4. PMID 38572751
• Lin J, Wu Q, Liu B, He H, Guo X, Li L, Jiang Y, Huang Y, Lin Y, He T, Zheng X, Li S, Chen L, Lin C, Li E, Zhou S, Sun Y. Neoadjuvant therapy of iparomlimab and tuvonralimab combined with chemotherapy-extenuated for locally advanced cervical cancer (NICE-CC): an investigator-initiated, multicentre, open-label, phase II trial. J Gynecol Oncol. 2026 Jul;37(4):e70. doi: 10.3802/jgo.2026.37.e70. Epub 2 PMID 41775252

Identifiers

NCT: NCT07055399 · NICE-CC trial

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗