iparomlimab and tuvonralimab (ql1706) for intermediate trophoblastic tumors

Conditions: Intermediate Trophoblastic Tumor

Summary: this clinical trial aims to evaluate the efficacy and safety of iparomlimab and tuvonralimab (ql1706), a dual-targeting immunotherapy (anti-pd-1/ctla-4), in patients with intermediate trophoblastic tumors (itt). the main questions it aims to answer are: does ql1706 improve complete response (cr) rates (primary endpoint) and survival outcomes? what are the safety profiles of ql1706 in itt, including immune-related adverse events? participants will receive ql1706 (5 mg/kg iv, q3w) ± chemotherapy (faev/ema/ep/ema/co/tp-te). they will also receive maintenance therapy post-hcg normalization. efficacy is assessed via serial β-hcg tests, imaging (every 9-12 weeks), and biomarker analysis.


Eligibility criteria:
inclusion criteria: females aged 18-70 years. histologically confirmed placental site trophoblastic tumor (pstt) or epitheloid trophoblastic tumor (ett) for cohort a: stage iv disease (treatment-naïve）, recurrent, or chemotherapy-resistant disease for cohort b: stage i-iii disease requiring adjuvant chemotherapy post-biopsy/surgery, meeting ≥1 of: abnormal β-hcg 2 weeks post-surgery; incomplete resection; high-risk features includes: interval from last pregnancy ≥48 months; deep myometrial invasion; mitotic count \>5/hpf; tumor necrosis. ecog score 0-1. signed informed consent. organ function requirements: hematologic: wbc ≥3.0×10⁹/l anc ≥1.5×10⁹/l platelets ≥80×10⁹/l hemoglobin ≥8.0 g/dl creatinine ≤1.5×uln total bilirubin ≤1.5×uln (or direct bilirubin ≤uln if total bilirubin \>1.5×uln) ast/alt ≤2.5×uln inr/pt/aptt ≤1.5×uln (or within therapeutic range if on anticoagulants). exclusion criteria: life expectancy \<3 months. non-gestational trophoblastic tumors. active malignancy (except if cured ≥3 years prior). prior immune checkpoint therapy (anti-pd-1/l1, ctla-4, icos, cd40, etc.) or cell-based immunotherapies. active autoimmune disease requiring systemic treatment (past 2 years). exceptions: hormone replacement (e.g., thyroxine), physiologic corticosteroids (≤10 mg/day prednisone equivalent). active inflammatory bowel disease (e.g., crohn's, ulcerative colitis). systemic corticosteroids (\>10 mg/day prednisone equivalent) within 14 days. allowed: topical/inhaled steroids, prophylactic steroids for contrast allergy. hiv/aids. active hepatitis: hbv dna \>1,000 iu/ml (unless on stable antiviral therapy with dna \<1,000 iu/ml). hcv rna-positive (unless cured). active tuberculosis (screening required if suspected). uncontrolled severe infection (e.g., sepsis, pneumonia requiring hospitalization). cardiovascular disease: nyha class iii/iv heart failure or lvef \<50%. uncontrolled hypertension (≥140/90 mmhg despite treatment). unstable angina, myocardial ischemia, or arterial thromboembolism (≤6 months). interstitial lung disease (history or active). malabsorption syndromes (e.g., chronic diarrhea, bowel obstruction) or gi perforation/fistula (≤6 months). psychiatric/social conditions impairing consent or compliance. allogeneic transplant history. live vaccines ≤30 days prior to ql1706 or planned during study. hypersensitivity to monoclonal antibodies or protocol-specified chemotherapies. pregnancy/lactation. other conditions deemed to compromise patient safety or study integrity.