Iparomlimab and Tuvonralimab (QL1706) for Intermediate Trophoblastic Tumors

Efficacy and Safety of Iparomlimab and Tuvonralimab (QL1706) in the Treatment of Intermediate Trophoblastic Tumors: A Prospective, Multicenter, Single-arm Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Intermediate Trophoblastic Tumor
• Intervention / Treatment: Drug: QL1706; Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yuan Li; Phone Number: +8617810376318; Email: liyuan10833@pumch.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Yang Xiang; Phone Number: 01069156068

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QL1706±chemo; Cohort A: QL1706: 5 mg/kg, intravenous (IV) infusion, every 3 weeks (Q3W), administered on Day 1 (D1).Chemotherapy Options: FAEV, EMA/EP, EMA/CO, or TP/TE. Cohort B: QL1706: 5 mg/kg, IV infusion, Q3W (D1).	Drug: QL1706; 5 mg/kg, IV infusion, Q3W (D1); Drug: Chemotherapy; FAEV, EMA/EP, EMA/CO, or TP/TE.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) Rate	Percentage of patients achieving CR, as defined by normalization of serum hCG (≤5 IU/L for ≥4 weeks)	up to one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Proportion of evaluable patients achieving CR + Partial Response (PR) (serum hCG decline >50% from baseline but without normalization)	up to one year
Disease Control Rate (DCR)	Proportion of evaluable patients with CR + PR + Stable Disease (SD) (serum hCG fluctuation ≤50% from baseline)	up to one year
Rate of Progression-Free Survival (PFS)	Time from treatment initiation to radiographic progression (RECIST v1.1) or death from any cause	up to one year
Rate of Overall Survival (OS)	Time from first dose to death from any cause	up to one year
Concentration of anti-Müllerian hormone (AMH) to assess ovarian function	Ovarian function as assessed by anti-Müllerian hormone (AMH)	up to one year
Number of Participants with treatment-related Adverse Events [Safety and Tolerability]	Determine frequency and severity of adverse events as assessed by NCI CTCAE (Version 5.0)	up to one year
Quality of life of cancer patients by questionnaire	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.	up to one year
Cancer specific rehabilitation by questionnaire	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.	up to one year
Reproductive concerns after cancer by scale	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	up to one year

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Henan Cancer Hospital; Shengjing Hospital; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; Sichuan Cancer Hospital and Research Institute; The First Affiliated Hospital of Xiamen University; Dalian women and children's medical group; Gansu Provincial Maternal and Child Health Care Hospital; Obstetrics & Gynecology Hospital of Fudan University (Shanghai Red House Ob & Gyn Hospital)

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2025
• Primary Completion (Estimated): April 16, 2027
• Study Completion (Estimated): April 16, 2028

Study Registration Dates

• First Submitted: April 15, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 26, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Neoplasms; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Germ Cell and Embryonal; Pregnancy Complications, Neoplastic; Trophoblastic Neoplasms
• Other Study ID Numbers: ITT01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No