Clinical trial NCT06941766: Iparomlimab and Tuvonralimab (QL1706) for Intermediate Trophoblastic Tumors
Official title: Efficacy and Safety of Iparomlimab and Tuvonralimab (QL1706) in the Treatment of Intermediate Trophoblastic Tumors: A Prospective, Multicenter, Single-arm Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Intermediate Trophoblastic Tumor
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Shengjing Hospital
name: Obstetrics & Gynecology Hospital of Fudan University (Shanghai Red House Ob & Gyn Hospital)
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Henan Cancer Hospital
name: Gansu Provincial Maternal and Child Health Care Hospital
name: Dalian women and children's medical group
name: The First Affiliated Hospital of Xiamen University
name: Sichuan Cancer Hospital and Research Institute
First posted: 2025-04-24
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Complete Response (CR) Rate
timeFrame: up to one year
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: up to one year
measure: Disease Control Rate (DCR)
timeFrame: up to one year
measure: Rate of Progression-Free Survival (PFS)
timeFrame: up to one year
measure: Rate of Overall Survival (OS)
timeFrame: up to one year
measure: Concentration of anti-Müllerian hormone (AMH) to assess ovarian function
timeFrame: up to one year
measure: Number of Participants with treatment-related Adverse Events [Safety and Tolerability]
timeFrame: up to one year
measure: Quality of life of cancer patients by questionnaire
timeFrame: up to one year
measure: Cancer specific rehabilitation by questionnaire
timeFrame: up to one year
measure: Reproductive concerns after cancer by scale
timeFrame: up to one year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: