QL706 + Chemo ± Bevacizumab in Anti-PD-(L)1-Resistant R/M Cervical Cancer

This is a prospective, open-label, single-arm, single-center phase II clinical trial investigating the efficacy and safety of a combination therapy in patients with recurrent or metastatic cervical cancer who have experienced disease progression following prior anti-PD-1/PD-L1 therapy.

The study aims to address the high unmet medical need in this patient population where treatment options are limited after failure of immunotherapy. The investigational regimen consists of iparomlimab and tuvonralimab (QL1706), a novel bifunctional antibody targeting both PD-1 and CTLA-4, combined with nab-paclitaxel chemotherapy, with the optional addition of bevacizumab at the investigator's discretion.

Approximately 25 participants will receive the combination treatment for 6 cycles (3-week cycles), followed by maintenance therapy with QL1706 ± bevacizumab until disease progression, unacceptable toxicity, or other discontinuation criteria are met. The primary endpoint is Objective Response Rate (ORR) per RECIST 1.1. Secondary endpoints include Progression-Free Survival (PFS), Duration of Response (DoR), Disease Control Rate (DCR), Overall Survival (OS), and safety profile. An exploratory objective will analyze the correlation between PD-L1 expression status and treatment outcomes.

The study will include rigorous safety monitoring per NCI CTCAE v5.0 guidelines and regular tumor assessments. The sample size was calculated based on the assumption of improving the ORR from a historical control of 15% to 40% with the new combination.

Inclusion criteria

• Female patients aged 18 to 75 years.
• Histologically, pathologically, or radiologically confirmed recurrent or metastatic cervical cancer.
• At least one measurable lesion as defined by RECIST 1.1 (non-nodal lesion longest diameter ≥10 mm or lymph node short axis ≥15 mm).
• ECOG performance status of 0 or 1.
• Life expectancy ≥12 weeks.
• Disease progression after receiving at least one prior anti-PD-1/PD-L1 monoclonal antibody therapy (alone or in combination).
• Adequate organ function within 14 days before enrollment:

Absolute neutrophil count (ANC) >1.5 × 10⁹/L Platelets >100 × 10⁹/L Hemoglobin >100 g/L Serum total bilirubin <1.5 × ULN ALT and AST <3 × ULN Creatinine clearance (CCr) >60 mL/min

• Voluntarily sign the informed consent form, able to understand and comply with study requirements.

Exclusion criteria

• Known allergy to any component of the study drugs.
• Prior treatment with any CTLA-4 targeting medication.
• Adverse reactions from previous anti-cancer therapy have not recovered to ≤ Grade 1 (per CTCAE v5.0) (except for toxicities without safety risk per investigator's judgment, e.g., alopecia).
• History of other malignancies within the past 5 years, except for cured malignancies.
• Severe comorbid conditions, including but not limited to:

Extensive interstitial lung disease requiring medication. Active or uncontrolled infections (e.g., tuberculosis, HIV). Decompensated liver disease, active hepatitis, or active bleeding. History of cerebrovascular accident or pulmonary embolism. Active, known, or suspected autoimmune diseases. Active infection requiring systemic anti-infective therapy.

• Ascites with depth >5 cm measured by ultrasound or CT, OR ascites causing severe symptoms (e.g., abdominal distension, dyspnea, circulatory dysfunction) significantly impacting physical function or study safety.
• Pregnant, planning pregnancy, or lactating women.
• Any other condition deemed by the investigator as unsuitable for participation in this study.