Intermediate Trophoblastic Tumor
Conditions
Brief 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.
Interventions
DRUGQL1706
5 mg/kg, IV infusion, Q3W (D1)
DRUGChemotherapy
FAEV, EMA/EP, EMA/CO, or TP/TE.
Sponsors
Shengjing Hospital
Obstetrics & Gynecology Hospital of Fudan University (Shanghai Red House Ob & Gyn Hospital)
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Henan Cancer Hospital
Gansu Provincial Maternal and Child Health Care Hospital
Dalian women and children's medical group
The First Affiliated Hospital of Xiamen University
Sichuan Cancer Hospital and Research Institute
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Rate | up to one year | Percentage of patients achieving CR, as defined by normalization of serum hCG (≤5 IU/L for ≥4 weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | up to one year | Proportion of evaluable patients with CR + PR + Stable Disease (SD) (serum hCG fluctuation ≤50% from baseline) |
| Rate of Progression-Free Survival (PFS) | up to one year | Time from treatment initiation to radiographic progression (RECIST v1.1) or death from any cause |
| Rate of Overall Survival (OS) | up to one year | Time from first dose to death from any cause |
| Concentration of anti-Müllerian hormone (AMH) to assess ovarian function | up to one year | Ovarian function as assessed by anti-Müllerian hormone (AMH) |
| Objective Response Rate (ORR) | up to one year | Proportion of evaluable patients achieving CR + Partial Response (PR) (serum hCG decline \>50% from baseline but without normalization) |
| Quality of life of cancer patients by questionnaire | up to one year | Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30(EORTC QLQ-C30) It consists of 30 questions across multiple scales, including a global health status scale and functional scales (physical, role, emotional, cognitive, and social functioning) to evaluate daily activities and well-being. Symptom scales cover common issues like fatigue, pain, and nausea. The tool's reliability and validity make it effective for measuring the impact of cancer and its treatments, with additional disease-specific modules available for tailored assessments. |
| Cancer specific rehabilitation by questionnaire | up to one year | Assessed by Cancer rehabilitation evaluation system-short form (CARES-SF) It is a brief, validated questionnaire designed to assess emotional well-being, functional status, and social support in cancer survivors. It is specifically tailored to evaluate the psychosocial and functional adjustment of individuals after cancer treatment, focusing on areas such as emotional distress, social functioning, and physical well-being. The tool is often used in oncology and rehabilitation settings to monitor the quality of life and recovery of cancer patients during and after treatment. It is concise, easy to administer, and provides valuable insights into the holistic needs of cancer survivors. |
| Reproductive concerns after cancer by scale | up to one year | Assessed by Reproductive Concerns After Cancer (RCAC) scale. The minimum and maximum values are 18 and 90 respectively, and a higher score means a higher level of reproductive concern or anxiety |
| Number of Participants with treatment-related Adverse Events [Safety and Tolerability] | up to one year | Determine frequency and severity of adverse events as assessed by NCI CTCAE (Version 5.0) |
Countries
China
Contacts
Primary ContactYuan Li
Outcome results
None listed