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

Not Applicable

Not yet recruiting

• Conditions: Cervical Cancer; Cervical Cancer Metastatic; Cervical Adenocarcinoma; Cervical Cancer Recurrent; Cervical Cancer Squamous Cell
• Interventions: Drug: QL1706 (bispecific antibody targeting PD-1 and CLTA-4)

• Registration Number: NCT07141186
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

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.

Study Timeline

• Study First Submitted: 2025-07-23
• Status Verified: 2025-08
• Study First Submitted QC: 2025-08-25
• Last Update Submitted: 2025-08-25
• Study First Posted: 2025-08-26
• Last Update Posted: 2025-08-26
• Study Start: 2025-10-01
• Primary Completion: 2027-10-01
• Study Completion: 2030-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 50

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PD-1/CTLA-4 bispecific antibody treatment group	QL1706 (bispecific antibody targeting PD-1 and CLTA-4)	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.

Primary Outcome Measures

Name	Time	Method
ORR	1-year	The objective response rate (ORR) assessed by the Independent Review Committee (IRC) (according to RECIST v1.1).

Secondary Outcome Measures

Name	Time	Method
DOR	1-year	The duration of response (DOR) assessed according to RECIST v1.1.
OS	1-year	Time from diagnosis of disease to 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
DCR	1-year	The disease control rate (DCR) assessed according to RECIST v1.1
PFS	1-year	Time from diagnosis of disease to disease progression or death due to any cause