Iparomlimab and Tuvonralimab Plus Paclitaxel and Platinum as Neoadjuvant Therapy for Locally Advanced Cervical Cancer (QUARTZ-CC)

Detailed Description Background Cervical cancer remains the fourth most common malignancy among women worldwide. In 2022, approximately 660,000 new cases and 350,000 deaths were reported globally, with the heaviest burden observed in developing regions, particularly Asia, which accounts for nearly 60% of global cases and deaths. China alone contributes 22.8% of global incidence and 16% of global mortality.

Locally advanced cervical cancer (LACC, FIGO stages IB3 and IIA2) constitutes approximately 50% of all cervical cancer cases in China. Current standard of care is concurrent chemoradiotherapy (CCRT); however, 23.3%-34.4% of patients still experience disease recurrence or metastasis. Neoadjuvant chemotherapy (NACT) followed by radical surgery has been investigated as an alternative strategy, yet 9.8%-30.6% of patients fail to respond to NACT, potentially delaying effective local treatment. Moreover, over 30% of patients who undergo surgery require adjuvant radiotherapy, raising concerns regarding treatment burden and health economics.In recent years, immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Anti-PD-1/PD-L1 and anti-CTLA-4 antibodies exert complementary mechanisms of action. Emerging evidence supports the combination of neoadjuvant chemotherapy and immunotherapy for LACC. In the PACS study (presented at ASCO 2024), the pathological complete response (pCR) rate was 36.2%, and the optimal pathological response rate (residual tumor <3 mm) was 53.2%. Other studies, including NACI, MITO CERV3, and NATCI, have reported similarly encouraging pCR rates. Given the unmet medical need for more effective and less toxic neoadjuvant regimens, further evaluation of novel immunotherapy combinations such as the dual PD-1/CTLA-4 bispecific antibody iparomlimab and tuvonralimab (QL1706) in combination with platinum-based chemotherapy is warranted.

Detailed Treatment and Response-Adapted Algorithm Following neoadjuvant treatment (up to 4 cycles of paclitaxel plus cisplatin or carboplatin combined with QL1706), patients undergo clinical assessment after 2 cycles. If tumor shrinkage is observed, patients continue for 2 additional cycles followed by imaging evaluation. Based on imaging response: complete response leads to cervical conization plus sentinel lymph node biopsy or pelvic lymph node dissection; partial response leads to radical hysterectomy or trachelectomy plus sentinel lymph node biopsy or pelvic lymph node dissection. Patients achieving optimal pathological response (defined as pathological complete response or residual tumor depth ≤3 mm) receive 2 additional cycles of the same regimen followed by QL1706 maintenance therapy for 8 cycles. Non-optimal responders receive adjuvant therapy per NCCN guidelines. Patients who cannot tolerate surgery or have contraindications receive radical radiotherapy.

Sample Size Justification and Statistical Framework The sample size was calculated using Simon's two-stage optimal design (one-sided alpha=0.05, power=80%; null hypothesis pCR=30% vs. alternative pCR=43%). The first stage enrolls 33 patients; if 10 or more pCR events are observed, enrollment continues to a total of 94 evaluable patients. Accounting for 10% dropout, total target enrollment is 103 patients.

Data and Safety Monitoring An independent Data Monitoring Committee will oversee patient safety and conduct periodic reviews. The Committee may recommend early termination for efficacy, futility, or safety concerns. The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, with written informed consent obtained from all participants.