Cervical Cancer, Immunotherapy, Neoadjuvant Therapy
Conditions
Brief summary
This is a prospective, single-arm, phase II clinical study designed to evaluate the efficacy and safety of QL1706 combined with cisplatin and paclitaxel as neoadjuvant therapy in patients with FIGO 2018 stage IB1-IB3 cervical cancer undergoing conservative surgery. The primary endpoint is pathological complete response (pCR). Secondary endpoints include objective response rate (ORR), progression-free survival (PFS), overall survival (OS), 3-year pelvic recurrence rate, and safety profile. Additionally, exploratory biomarker analyses will be conducted to investigate changes in immune status, genomic alterations, PD-L1 expression, tumor mutational burden, MSI-H/dMMR status, and vaginal microbiota before and after treatment.
Detailed description
Cervical cancer remains one of the most common gynecologic malignancies worldwide. Neoadjuvant chemotherapy (NACT) has demonstrated favorable response rates in locally advanced cervical cancer; however, pathological complete response (pCR) rates remain limited. QL1706 is a novel bifunctional PD-1/CTLA-4 antibody combination developed using the MabPair® platform. It consists of the anti-PD-1 antibody iparomlimab and the anti-CTLA-4 antibody tuvonralimab. Previous studies have demonstrated promising antitumor activity in recurrent or metastatic cervical cancer. This study aims to investigate whether the addition of QL1706 to cisplatin/paclitaxel neoadjuvant therapy can improve pathological response and clinical outcomes in patients with FIGO 2018 stage IB1-IB3 cervical cancer undergoing conservative surgery. Approximately 50 patients will be enrolled. Eligible patients will receive neoadjuvant QL1706 combined with cisplatin and paclitaxel followed by radical surgery. Efficacy will be evaluated using RECIST v1.1 and pathological assessment. Safety will be assessed according to CTCAE v5.0. Exploratory translational studies will evaluate immune microenvironment changes, molecular biomarkers, and vaginal microbiota alterations associated with treatment response.
Interventions
DRUGQL1706 + Cisplatin/Paclitaxel Neoadjuvant Therapy
QL1706 is a bifunctional PD-1/CTLA-4 antibody combination consisting of iparomlimab and tuvonralimab. Drug: Cisplatin Cisplatin administered as part of neoadjuvant chemotherapy. Drug: Paclitaxel Paclitaxel administered as part of neoadjuvant chemotherapy.
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Female patients aged 18-65 years. * Histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma. * FIGO 2018 stage IB1, IB2, or IB3 cervical cancer. * Pelvic MRI completed before enrollment. * ECOG performance status of 0-2. * Adequate organ and bone marrow function. * No prior immunotherapy for malignant tumors. * Ability to understand and willingness to sign written informed consent.
Exclusion criteria
* Presence of uncontrolled concomitant malignancies. * Active autoimmune disease or history of autoimmune disease with potential recurrence. * Interstitial lung disease or uncontrolled pneumonitis. * Active hepatitis B or hepatitis C infection. * Known HIV infection. * Receipt of live vaccines within 30 days before first dose. * Uncontrolled cardiovascular disease. * Known hypersensitivity to study drugs. * Any condition that, in the investigator's judgment, may interfere with study participation or interpretation of results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) | At surgery following completion of neoadjuvant therapy | Proportion of patients achieving pathological complete response after neoadjuvant therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | During neoadjuvant treatment period | Proportion of patients achieving complete or partial response according to RECIST v1.1. |
| Progression-Free Survival (PFS) | Up to 3 years | Time from treatment initiation to disease progression or death. |
| 3-Year Pelvic Recurrence Rate | 3 years | Proportion of patients with pelvic recurrence within 3 years. |
| Adverse Events | From informed consent through 30 days after last treatment dose | Incidence and severity of adverse events graded according to CTCAE v5.0. |
| Overall Survival (OS) | Up to 3 years | Time from treatment initiation to death from any cause |
Contacts
CONTACTZhigang Zhang, MD
PRINCIPAL_INVESTIGATORJianwei Zhou, PhD
Second Affiliated Hospital, School of Medicine, Zhejiang University
Outcome results
None listed