Cervical Cancer, Cervical Cancer Metastatic, Cervical Cancer Recurrent, Cervical Adenocarcinoma, Cervical Cancer Squamous Cell
Conditions
Keywords
cervical cancer, immunotherapy, PD-1/CTLA-4 bispecific antibody, QL1706, PD-1 resistant
Brief summary
To explore the efficacy and safety of administrating QL1706 in patients with recurrent and/or metastatic cervical cancer who had developed resistance to prior PD-1/PD-L1 antibody therapies.
Detailed description
The application of PD-1/PD-L1 antibodies in cervical cancer is becoming increasingly widespread. However, monotherapy with PD-1 inhibitors demonstrates only a 10-20% response rate and a median progression-free survival of merely 2 months in patients with recurrent or metastatic cervical cancer. To address the issue of resistance to PD-1/PD-L1 antibodies in cervical cancer patients, we plan to conduct a clinical study. This study will administer a PD-1/CTLA-4 bispecific antibody to patients with recurrent or metastatic cervical cancer who are resistant to PD-1/PD-L1 therapy, thereby evaluating the efficacy and safety profile of the bispecific antibody in this specific patient population.
Interventions
Enrolled patients will receive intravenous infusion of QL1706 once every 3 weeks at a dose of 5.0 mg/kg until disease progression, death, intolerable treatment toxicity, or withdrawal from the clinical trial for any reason.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with recurrent/metastatic cervical cancer who previously experienced failure of PD-1 blockade therapy; 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; 3. Life expectancy ≥3 months; 4. At least one measurable lesion per RECIST v1.1: Non-lymph node lesion: Longest diameter ≥10 mm Lymph node lesion: Short-axis diameter ≥15 mm Note: Previously irradiated lesions must be outside radiation fields or demonstrate progression post-radiation. 5. Adequate organ function within 14 days prior to treatment: 1. Absolute neutrophil count (ANC) ≥1.0×10⁹/L 2. Hemoglobin ≥60 g/L 3. Platelet count ≥50×10⁹/L 4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3×ULN (≤5×ULN for hepatic metastasis) 5. Serum creatinine ≤2×ULN 6. Reproductive requirements: 1. Non-childbearing potential (surgically sterilized or postmenopausal) OR 2. Women of childbearing potential: Negative serum pregnancy test within 7 days prior to enrollment Commitment to use double-barrier contraception throughout the study and for 180 days post-treatment 7. Ability to comply with scheduled visits, treatment plans, and laboratory tests; 8. Voluntarily signed written informed consent.
Exclusion criteria
1. Prior treatment with anti-PD-1/CTLA-4 bispecific antibodies; 2. Active autoimmune disease requiring systemic control with corticosteroids (≥10 mg/day prednisone equivalent) or immunosuppressants within 14 days prior to enrollment; 3. Clinically significant cardiovascular/cerebrovascular events within 6 months prior to treatment, including: 1. Acute myocardial infarction 2. Unstable angina 3. Cerebrovascular accident 4. Symptomatic arterial/venous thrombosis or ischemic cardiomyopathy 5. Clinically significant ventricular arrhythmias (sustained VT, VF, torsades de pointes) 6. NYHA Class III/IV heart failure 7. QTcF ≥480 ms or congenital long QT syndrome 8. LVEF \<50% or severe wall motion abnormality per echocardiography 9. Uncontrolled hypertension (SBP \>160 mmHg or DBP \>100 mmHg) 10. Other clinically significant arrhythmias (e.g., third-degree AV block); 4. Uncontrolled comorbidities potentially affecting protocol compliance: * Severe respiratory diseases (ILD, severe asthma) * Active infections: * HBV (HBsAg+ AND HBV-DNA \>500 IU/mL) * HCV (HCV-Ab+ AND HCV-RNA+) * HIV-Ab+ * Active TB or systemic infections requiring treatment ≤14 days * GI perforation/fistula ≤6 months (exceptions: resolved surgically) * Clinically significant bleeding ≤1 month (hematemesis, hemoptysis, etc.) * Active diverticulitis, abdominal abscess, or bowel obstruction; 5. Other malignancies within 3 years (excluding cured BCC, superficial bladder Ca, DCIS, or papillary thyroid Ca); 6. Known immunodeficiency disorders; 7. History of allogeneic hematopoietic stem cell or solid organ transplantation (excluding corneal grafts); 8. Systemic infections requiring IV antibiotics \>7 days within 2 weeks prior to treatment; 9. Administration of live attenuated vaccines within 4 weeks before/after treatment; 10. Pregnancy or lactation; 11. Investigator-assessed ineligibility; 12. Concurrent participation in other clinical trials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 1-year | The objective response rate (ORR) assessed by the Independent Review Committee (IRC) (according to RECIST v1.1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DOR | 1-year | The duration of response (DOR) assessed according to RECIST v1.1. |
| DCR | 1-year | The disease control rate (DCR) assessed according to RECIST v1.1 |
| OS | 1-year | Time from diagnosis of disease to death due to any cause |
| PFS | 1-year | Time from diagnosis of disease to disease progression or death due to any cause |
| Profile of adverse events | 3 years | Frequency and severity of treatment-related toxicities, whether immune-related or non-immune-related |
Contacts
Primary ContactChen Li
Outcome results
None listed