QL1706 in Patients With Recurrent and Metastatic Cervical Cancer Resistant to Prior PD-1/PD-L1 Antibody Therapy

Tianjin Medical University

Status and phase: Not yet enrolling; Phase 2

Conditions: Cervical Adenocarcinoma; Cervical Cancer Metastatic; Cervical Cancer Squamous Cell; Cervical Cancer Recurrent; Cervical Cancer

Treatments: Drug: QL1706 (bispecific antibody targeting PD-1 and CLTA-4)

Study type: Interventional

Funder types: Other

Identifiers

NCT07141186

2020250707083952035

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

PD-1/CTLA-4 bispecific antibody treatment group

Experimental group

Description:

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.

Treatment:

Drug: QL1706 (bispecific antibody targeting PD-1 and CLTA-4)