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

Official title

A Prospective, Single-Arm, Phase II Trial of QL1706 in Patients With Recurrent and/or Metastatic Cervical Cancer Who Had Developed Resistance to Prior PD-1/PD-L1 Antibody Therapy

Overview

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

• Drug 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

• ORR [Time frame: 1-year]

Secondary outcome measures (5)

• DOR [Time frame: 1-year]
• DCR [Time frame: 1-year]
• OS [Time frame: 1-year]
• PFS [Time frame: 1-year]
• Profile of adverse events [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Patients with recurrent/metastatic cervical cancer who previously experienced failure of PD-1 blockade therapy;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Life expectancy ≥3 months;
• 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.

• Adequate organ function within 14 days prior to treatment:

• Absolute neutrophil count (ANC) ≥1.0×10⁹/L
• Hemoglobin ≥60 g/L
• Platelet count ≥50×10⁹/L
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3×ULN (≤5×ULN for hepatic metastasis)
• Serum creatinine ≤2×ULN
• Reproductive requirements:

• Non-childbearing potential (surgically sterilized or postmenopausal) OR
• 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

• Ability to comply with scheduled visits, treatment plans, and laboratory tests;
• Voluntarily signed written informed consent.

Exclusion criteria

• Prior treatment with anti-PD-1/CTLA-4 bispecific antibodies;
• Active autoimmune disease requiring systemic control with corticosteroids (≥10 mg/day prednisone equivalent) or immunosuppressants within 14 days prior to enrollment;
• Clinically significant cardiovascular/cerebrovascular events within 6 months prior to treatment, including:

• Acute myocardial infarction
• Unstable angina
• Cerebrovascular accident
• Symptomatic arterial/venous thrombosis or ischemic cardiomyopathy
• Clinically significant ventricular arrhythmias (sustained VT, VF, torsades de pointes)
• NYHA Class III/IV heart failure
• QTcF ≥480 ms or congenital long QT syndrome
• LVEF <50% or severe wall motion abnormality per echocardiography
• Uncontrolled hypertension (SBP >160 mmHg or DBP >100 mmHg)
• Other clinically significant arrhythmias (e.g., third-degree AV block);
• 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;
• Other malignancies within 3 years (excluding cured BCC, superficial bladder Ca, DCIS, or papillary thyroid Ca);
• Known immunodeficiency disorders;
• History of allogeneic hematopoietic stem cell or solid organ transplantation (excluding corneal grafts);
• Systemic infections requiring IV antibiotics >7 days within 2 weeks prior to treatment;
• Administration of live attenuated vaccines within 4 weeks before/after treatment;
• Pregnancy or lactation;
• Investigator-assessed ineligibility;
• Concurrent participation in other clinical trials.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07141186 · 2020250707083952035

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗