This is a clinical research study for women with recurrent or metastatic cervical cancerwhose disease has progressed after prior treatment with a PD-1/PD-L1 inhibitorimmunotherapy.The study will evaluate the effectiveness and safety of a new combination treatmentconsisting of iparvolimab and tuvonralimab (QL1706)-a dual-targeting immunotherapydrug-along with chemotherapy (nab-paclitaxel) with or without bevacizumab, ananti-angiogenic drug that may help prevent tumor growth.Approximately 25 participants will be enrolled in this open-label, single-arm study. Allparticipants will receive the study treatment for up to 6 cycles, followed by maintenancetherapy until disease progression, unacceptable side effects, or other reasons forstopping treatment.The main goal of the study is to see how many patients respond to the treatment(Objective Response Rate, ORR). Other goals include measuring how long the responselasts, how long patients live without the cancer getting worse, and overall survival.Safety and quality of life will also be closely monitored.This study is for women aged 18-75 who have previously received PD-1/PD-L1 treatment andwhose cancer has worsened. Participants must be in generally good health with adequateorgan function and no other active cancers.The study will be conducted at a single center in China. All participants will providewritten informed consent before joining the study.
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.
Biological: Iparomlimab and Tuvonralimab (QL1706) + Nab-Paclitaxelwith or without Bevacizumab
All participants will receive the study intervention: Iparomlimab and Tuvonralimab
(QL1706) at 5.0 mg/kg IV Q3W + Nab-Paclitaxel at 260 mg/m² IV Q3W, with or without
Bevacizumab (7.5-15 mg/kg IV Q3W) per investigator's choice, for 6 cycles. This is
followed by maintenance therapy with QL1706 ± Bevacizumab until disease progression,
unacceptable toxicity, or other discontinuation criteria are met.
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.
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