Cervical cancer
Conditions
Interventions
Trial group (Cohort 1):Sacituzumab tirumotecan (Sac-TMT/SKB264) 4 mg/kg, administered by intravenous infusion (IV) on Day 1 of each cycle, every 2 weeks (Q2W), Qlipotolimod (QL1706) 3 mg/kg, administe
Trial group (Cohort 2):Sacituzumab tirumotecan (Sac-TMT/SKB264) 4 mg/kg, administered by intravenous infusion (IV) on Day 1 of each cycle, every 2 weeks (Q2W)
Qlipotolimod (QL1706) 3 mg/kg, administered by intravenous infusion (IV) on Day 1 of each cycle, every 2 weeks (Q2W).
Sponsors
Fujian Cancer Hospital
Eligibility
Sex/Gender
Female
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Female, >=18 years of age at the time of informed consent. 2.Histologically confirmed recurrent or metastatic cervical cancer—pathologic types include squamous cell carcinoma, adenocarcinoma (excluding mucinous adenocarcinoma), and adenosquamous carcinoma—with pathology report available; not a candidate for curative surgery or radiotherapy. Participants will be assigned to histology-based cohorts: (1)Cohort 1: Cervical squamous cell carcinoma. (2)Cohort 2: Cervical non-squamous carcinoma (including adenocarcinoma or adenosquamous carcinoma, and other cervical cancer histologies). 3.Prior therapy requirements at the recurrent/metastatic stage: disease that has failed at least one line of platinum-based standard therapy or is intolerant to platinum, or radiologically confirmed disease progression within 6 months during or after >=4 cycles of platinum-based neoadjuvant or adjuvant chemotherapy. Details: (1) Failure of first-line platinum-based standard therapy (meet >=1): 1)Radiologically confirmed progression during treatment; or 2) Clinical benefit (CR/PR/SD) with >=4 cycles received, followed by radiologically confirmed progression after treatment completion. (2) Intolerance to platinum-based therapy, per investigator judgment. (3) Radiologically confirmed progression within 6 months during or after >=4 cycles of platinum-based neoadjuvant or adjuvant chemotherapy. Weekly cisplatin administered as a radiosensitizer during concurrent chemoradiotherapy does not count toward chemotherapy cycles. 4.At least one measurable lesion per RECIST v1.1 (non-nodal lesion with longest diameter >=10 mm, or lymph-node short axis =15 mm). Previously irradiated lesions should not be selected as target lesions; if no other measurable lesions exist, a previously irradiated measurable lesion may be selected as a target only if progression is radiographically confirmed. Patients with only cutaneous lesions or only bone lesions are ineligible. 5.ECOG performance status of 0–1 within 7 days before first dose. 6.Estimated life expectancy >=12 weeks. 7.Recovery from all toxicities of prior therapy to Grade 0–1 (or to the levels specified in these criteria), except for toxicities not considered a safety risk (e.g., alopecia, vitiligo, and other asymptomatic laboratory abnormalities). Patients with =1.5 × 10^9/L; platelets >=100 × 10^9/L; hemoglobin >=90 g/L. (2)Hepatic: AST and ALT =30 g/L; total bilirubin =50 mL/min (calculated by the standard Cockcroft–Gault formula); urine protein =2+, 24-hour urinary protein =50%. 9.Women of childbearing potential agree to use effective contraception from signing informed consent through 6 months after the last dose (see Appendix 2 for acceptable methods). Willing and able to provide written informed consent and comply with the protocol-specified visits and procedures.
Exclusion criteria
Exclusion criteria: 1.History of another known malignancy within the past 5 years that is progressing or requires active treatment; exceptions include malignancies that have received potentially curative therapy, such as adequately treated basal cell carcinoma or squamous cell carcinoma of the skin. 2.Known leptomeningeal, brainstem, or spinal cord metastases and/or compression, or other active central nervous system (CNS) metastases. Patients with brain metastases treated locally may be enrolled if clinically stable for =4 weeks and not requiring corticosteroids for at least 14 days before the first dose. 3.Clinically significant cardiovascular disease, such as: (1) severe or uncontrolled cardiac disease or symptoms within 6 months before first dosing, including New York Heart Association (NYHA) class III or IV congestive heart failure, unstable angina refractory to medication, severe arrhythmias requiring medication (excluding atrial fibrillation or paroxysmal supraventricular tachycardia), or myocardial infarction; (2) prior myocarditis or cardiomyopathy; (3) baseline QTc interval >480 ms. 4.Severe and/or uncontrolled comorbid conditions, such as decompensated cirrhosis, nephrotic syndrome, poorly controlled hypertension, or clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring repeated drainage. 5.Active hepatitis B or hepatitis C infection. 6.Known, poorly controlled human immunodeficiency virus (HIV) infection, including HIV with a history of Kaposi sarcoma and/or multicentric Castleman disease. 7.Known active tuberculosis. 8.History of severe dry eye syndrome, meibomian gland dysfunction, blepharitis, or corneal diseases that impair timely corneal healing. 9.Known prior female genital tract fistula (e.g., vesicovaginal, urethrovaginal, vesicocervical). Patients whose perforation or fistula has been diverted, resected, or repaired and is considered resolved or improved by the investigator may be eligible. 10.Major surgery (as defined by the investigator) within 30 days before first dosing, or not fully recovered from prior surgery. 11.Known allergy or hypersensitivity to study drugs or their excipients; history of severe hypersensitivity to monoclonal antibodies. 12.History of interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroids; current ILD/pneumonitis; or suspected ILD/pneumonitis at screening that cannot be excluded by imaging. 13.History of allogeneic tissue/organ transplantation. 14.Autoimmune disease requiring systemic therapy within the past 2 years or expected to require immunosuppressive treatment during the study. Patients with controlled type 1 diabetes, thyroiditis with euthyroid function, hypothyroidism well controlled with hormone replacement therapy (HRT), or skin conditions not requiring systemic therapy (e.g., vitiligo, psoriasis) may be included. 15.Prior therapy targeting TROP2 or any topoisomerase I–containing therapy, including antibody–drug conjugates (ADCs). 16.Prior receipt of any investigational anticancer vaccine, or any agent targeting T-cell co-stimulatory pathways. 17.Receipt of a live vaccine within 30 days before first dosing, or planned receipt of a live vaccine during the study. 18.Use of strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 2 weeks before first dosing or during the study. 19.Chemotherapy, radiotherapy, immunotherapy, or biologic therapy within 4 weeks before first dosing; receipt of small-molecule tyrosine kinase inhibitors (TKI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS);Progression-Free (PFS);Disease Control Rate (DCR);Duration of Response (DoR);Safety (including the incidence of all adverse events, treatment-emergent adverse events, and serious adverse events, et al); | — |
Countries
China
Contacts
Public ContactXu Qin
Fujian Cancer Hospital
Outcome results
None listed