Iparomlimab and Tuvonralimab Plus Paclitaxel and Platinum as Neoadjuvant Therapy for Locally Advanced Cervical Cancer

NCT07646301 | Recruiting Phase 2 DMC

• 1 other identifier: B2026-154-01
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: To evaluate the efficacy and safety of neoadjuvant treatment with iparomlimab and tuvonralimab (QL1706), a dual PD1and CTLA4 bispecific antibody, in combination with paclitaxel and either cisplatin or carboplatin (TP/TC regimen) for patients with locally advanced cervical cancer. Eligibility Criteria: Women aged 18 to 70 years with newly diagnosed, histologically confirmed cervical cancer (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma), FIGO stage IB3 or IIA2, with no evidence of significant lymph node involvement (pelvic and paraaortic lymph nodes \<1.5 cm in short diameter), and who have not received any prior anticancer therapy. Study Procedures: Participants will receive up to 4 cycles of QL1706 plus TP/TC chemotherapy (once every 3 weeks) prior to surgery. After 2 cycles, clinical assessment will be performed to evaluate tumor response. If tumor shrinkage is observed, treatment may continue for 2 additional cycles, followed by imaging evaluation. Depending on the response, participants with complete or partial response may undergo less extensive surgery (cervical conization plus sentinel lymph node biopsy) rather than standard radical hysterectomy. After surgery, participants who achieve a major pathological response will receive QL1706 maintenance therapy as a single agent for up to 8 additional cycles (once every 3 weeks). For participants with insufficient tumor response, standard radical hysterectomy will be performed. Postoperative adjuvant therapy (radiation or chemotherapy) will follow standard clinical guidelines. Primary and Secondary Objectives: The primary endpoint is the pathological complete response (pCR) rate in the resected tissue following neoadjuvant treatment. Secondary endpoints include safety (treatment related adverse events), objective response rate (ORR), 3 years overall survival, 3 years disease free survival, and quality of life. Study Duration: Total participation time depends on treatment response and surgical scheduling, with an expected duration of approximately 9 to 12 months (including neoadjuvant treatment, surgery, and potential maintenance therapy).

Conditions

Uterine Cervical Neoplasms; Locally Advanced

Keywords

Locally advanced cervical cancer; QL1706; Neoadjuvant chemoimmunotherapy; Pathological complete response; Phase II Single-arm Prospective study; QUARTZ-CC

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) Rate

  Proportion of patients with no residual invasive tumor cells in the surgically resected primary tumor specimen following neoadjuvant therapy.

  At the time of surgery, following completion of neoadjuvant treatment (each cycle is 21 days; patients receive 2 to 4 cycles)

Secondary Outcomes (7)

• Major Pathological Response (MPR) Rate

  At the time of surgery, following completion of neoadjuvant treatment (each cycle is 21 days)

• Objective Response Rate (ORR)

  After 4 cycles of neoadjuvant treatment (each cycle is 21 days)

• 3-Year Overall Survival (OS) Rate

  From date of first dose to date of death from any cause, assessed up to 36 months

• 3-Year Disease-Free Survival (DFS) Rate

  From date of surgery to date of recurrence or death, assessed up to 36 months

• Treatment-Related Adverse Events (TRAEs)

  From first dose of study treatment until 90 days after last dose (each cycle is 21 days; up to 6 neoadjuvant cycles + up to 8 maintenance cycles; total up to approximately 12 months).

Other Outcomes (2)

• Predictive Biomarkers of Response

  Baseline and at time of surgery

• Changes in Ovarian Function in Younger Patients

  Baseline and within 1 month after surgery

Study Arms (1)

QL1706 + TP/TC Neoadjuvant Chemoimmunotherapy

EXPERIMENTAL

Participants receive up to 4 cycles of neoadjuvant therapy (once every 3 weeks) with iparomlimab and tuvonralimab (QL1706 250 mg, IV) plus paclitaxel (150-175 mg/m², IV) and either cisplatin (70-75 mg/m², IV, split over 2 days) or carboplatin (AUC=5, IV). Treatment response is assessed after 2 cycles. For patients achieving tumor shrinkage, neoadjuvant therapy continues for 2 additional cycles followed by imaging. Patients achieving complete response (CR) undergo cervical conization plus sentinel lymph node biopsy (SLNB) or pelvic lymph node dissection (PLND). Those achieving partial response (PR) or non-optimal pathological response after surgery undergo radical hysterectomy/trachelectomy plus SLNB/PLND. Participants who achieve optimal pathological response (pCR or residual tumor depth ≤3 mm) after surgery receive QL1706 maintenance therapy for up to 8 cycles (once every 3 weeks). Patients who cannot tolerate surgery or have contraindications undergo radical radiotherapy.

Drug: Iparomlimab and Tuvonralimab (QL1706); Drug: Paclitaxel; Drug: Cisplatin; Drug: Carboplatin

Interventions

Paclitaxel DRUG

150-175 mg/m² administered intravenously over at least 3 hours on Day 1 of each 21-day cycle for up to 4 cycles, with standard premedication to prevent hypersensitivity.

QL1706 + TP/TC Neoadjuvant Chemoimmunotherapy

Iparomlimab and Tuvonralimab (QL1706) DRUG

250 mg administered intravenously over at least 30 minutes on Day 1 of each 21-day cycle for up to 4 cycles as neoadjuvant therapy, and up to 8 cycles as maintenance therapy (for patients achieving optimal pathological response).

QL1706 + TP/TC Neoadjuvant Chemoimmunotherapy

Cisplatin DRUG

70-75 mg/m² administered intravenously over at least 1 hour, split over two consecutive days (Day 1 and Day 2) of each 21-day cycle for up to 4 cycles. Cisplatin or Carboplatin according to investigator's choice

QL1706 + TP/TC Neoadjuvant Chemoimmunotherapy

Carboplatin DRUG

AUC=5 administered intravenously over at least 1 hour on Day 1 of each 21-day cycle for up to 4 cycles. Cisplatin or Carboplatin according to investigator's choice

QL1706 + TP/TC Neoadjuvant Chemoimmunotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 70 years.
• Histologically or cytologically confirmed cervical cancer, FIGO stage IB3 or IIA2.
• Imaging findings showing pelvic lymph node short-axis diameter \< 1.5 cm and para-aortic lymph node short-axis diameter \< 1.5 cm.
• Pathological diagnosis of cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma.
• No prior anti-tumor therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

You may not qualify if:

• Presence of other concurrent malignancies.
• Pregnant or peripartum women.
• History of myocardial infarction or stroke, unstable angina, decompensated heart failure, or deep vein thrombosis.
• Presence of NCI-CTCAE version 5.0 grade ≥2 arrhythmia, any grade of atrial fibrillation, or clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
• Active unresolved hepatitis, defined as progressive decrease in appetite, general weakness, nausea, acid reflux, aversion to oily foods, abdominal distension, or abnormal liver function with jaundice (e.g., scleral or urinary jaundice); for hepatitis B, HBV DNA \> 1000 IU/mL.
• Hepatic insufficiency (aspartate aminotransferase/alanine aminotransferase \> 2.5 × upper limit of normal).
• Renal insufficiency (serum creatinine \> 2 × upper limit of normal).
• History of chronic pulmonary disease with restrictive respiratory dysfunction.
• History of major organ transplantation or autoimmune disease.
• History of severe mental illness or cerebral dysfunction.
• History of substance abuse or drug addiction.
• Use of immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes (dose \> 10 mg prednisone or equivalent) within 2 weeks prior to enrollment, with ongoing use.
• Coagulation abnormality (INR \> 2.0, PT \> 16 seconds), bleeding tendency, or ongoing thrombolytic or anticoagulant therapy (prophylactic low-dose aspirin and low-molecular-weight heparin are permitted).
• Congenital or acquired immunodeficiency (e.g., HIV infection).
• Receipt of inactivated vaccine within 30 days prior to the first dose of study treatment.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (4)

• Lou H, Zhou Y, Li D, et al. 251 Efficacy and safety of iparomlimab and tuvonralimab in previously treated patients with recurrent or metastatic cervical cancer: a multicenter, open-label, single-arm, phase 2 clinical trial (DUBHE-C- 206). Int J Gynecol Cancer. 2024;34(Suppl 1):A5.1.

  RESULT

• Pan YC, Dai Z, Ma H, Zheng J, Leng J, Xie C, Yuan Y, Yang W, Yalikun Y, Song X, Han CB, Shang C, Yang Y. Self-powered and speed-adjustable sensor for abyssal ocean current measurements based on triboelectric nanogenerators. Nat Commun. 2024 Jul 20;15(1):6133. doi: 10.1038/s41467-024-50581-w.

  PMID: 39033189 RESULT

• Cui B, Xian C, Han B, Shu C, Qian Y, Ouyang Z, Wang X. High-resolution emission inventory of biogenic volatile organic compounds for rapidly urbanizing areas: A case of Shenzhen megacity, China. J Environ Manage. 2024 Feb;351:119754. doi: 10.1016/j.jenvman.2023.119754. Epub 2023 Dec 10.

  PMID: 38071916 RESULT

• Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.

  PMID: 2702835 RESULT

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Paclitaxel; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes

Central Study Contacts

Jihong Liu, Ph.D.

CONTACT

+86 20 87341779; liujih@sysucc.org.cn

Yun Zhou, M.D.

CONTACT

+86 20 87343105; zhouyun@sysucc.or.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a single-arm, open-label, Simon's two-stage optimal design. In the first stage, 33 patients will be enrolled. If 10 or more patients achieve pathological complete response (pCR), the study will proceed to the second stage, enrolling additional patients to reach a total of 94 evaluable patients (accounting for 10% dropout, total enrollment target is 103). The primary endpoint is pCR rate

Study Record Dates

• First Submitted: May 31, 2026
• First Posted: June 12, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: June 12, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)