Clinical trial NCT07002346: INVIGORATE: A Study of QL1706 and Bevacizumab in Advanced First-Line Ovarian Clear Cell Carcinoma
Official title: Randomized Active-controlled Trial Evaluating QL1706 Plus Bevacizumab Versus Platinum-Based Chemotherapy for Advanced First-Line Ovarian Clear Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Ovarian Clear Cell Carcinoma
Keywords: Ovarian Clear Cell Carcinoma
QL1706
Bevacizumab
First-line treatment
Immunotherapy
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: Chinese Academy of Medical Sciences
name: Peking Union Medical College Hospital
name: Fudan University Shanghai Cancer Center ( FUSCC )
name: Sun Yat-sen University Cancer Center (SUSUCC)
name: Peking University Cancer Hospital & Institute
name: Peking University People's Hospital
name: First Affiliated Hospital, Sun Yat-Sen University
name: The Second Affiliated Hospital, Sun Yat-sen University
name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Fudan University
name: Renmin Hospital of Wuhan University
name: Zhejiang Provincial People's Hospital
name: Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center
name: Shanghai First Maternity and Infant Hospital
name: Hubei Cancer Hospital
name: Sir Run Run Shaw Hospital
name: Wuhan Central Hospital
name: Zhejiang Cancer Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Third Affiliated Hospital of Zhengzhou University
name: Henan Provincial People's Hospital
name: Henan Cancer Hospital
name: Jiangsu Cancer Institute & Hospital
name: The International Peace Maternity & Child Health Hospital of China welfare institute
name: Women's Hospital School Of Medicine Zhejiang University
name: Wuhan Union Hospital, China
name: First Affiliated Hospital of Zhejiang University
First posted: 2025-06-03
Enrollment: 226
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if QL1706 combined with bevacizumab can effectively treat adult female patients (18 to \<75 years old) with newly diagnosed FIGO stage IC-IV advanced ovarian clear cell carcinoma. The main questions it aims to answer are:

1. Does QL1706 combined with bevacizumab, compared to platinum-based chemotherapy, prolong patients' progression-free survival (PFS)?
2. What is the safety profile of QL1706 combined with bevacizumab, such as what medical problems (adverse events) do participants experience?

Researchers will compare QL1706 combined with bevacizumab (experimental arm) to a standard chemotherapy regimen of paclitaxel plus carboplatin (control arm) to see if QL1706 combined with bevacizumab is more effective in the first-line treatment of advanced ovarian clear cell carcinoma.

Participants will:

1. Be randomly assigned to receive either QL1706 combined with bevacizumab (QL1706 administered every 3 weeks, bevacizumab administered every 3 weeks) or paclitaxel plus carboplatin chemotherapy (administered every 3 weeks).
2. Visit the research center regularly for drug infusions, medical examinations (such as vital signs, physical exams, laboratory tests), and tumor imaging assessments.
3. Complete quality of life questionnaires as required.


Eligibility criteria: Inclusion Criteria:

* Voluntary participation in the study and signed informed consent form.
* Age ≥ 18 years and \< 75 years, female.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Expected survival ≥ 3 months.
* Histologically or cytologically newly diagnosed FIGO stage IC-IV ovarian clear cell carcinoma.
* Patients who have undergone primary debulking surgery or interval debulking surgery after neoadjuvant chemotherapy, regardless of whether satisfactory debulking was achieved.
* No prior treatment with immune checkpoint inhibitors.
* Adequate organ function confirmed by the following requirements:

Hematological (no use of any blood components or cell growth factors within 7 days prior to initiation of study treatment):

i. Absolute neutrophil count (ANC) ≥ 10\^9/L (1,500/mm\^3). ii. Platelet count ≥ 100 × 10\^9/L (100,000/mm\^3). iii. Hemoglobin ≥ 90 g/L.

Renal:

i. Calculated creatinine clearance (CrCl) \* ≥ 50 mL/min.

* CrCl will be calculated using the Cockcroft-Gault formula: CrCl (mL/min) = (\[(140 - age) \* weight (kg) \* F\] / \[SCr (mg/dL) \* 72\]) Where F=0.85 (for females); SCr = serum creatinine.

ii. Urine protein \< 2+ or 24-hour (h) quantitative urine protein \< 1.0 g.

Hepatic:

i. Total serum bilirubin (TBil) ≤ 1.5 × ULN (Upper Limit of Normal). ii. AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) ≤ 2.5 × ULN.

Coagulation:

i. International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.

- For women of childbearing potential, a negative serum or urine pregnancy test within one week prior to enrollment, and effective contraceptive measures must be used after enrollment, for example: use of physical barrier contraception (condoms) or complete abstinence. Oral, injectable, or implantable hormonal contraceptives are not permitted. Or, women of non-childbearing potential, defined as: i. Naturally postmenopausal for at least 1 year. ii. Surgically sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).

iii. Serum follicle-stimulating hormone, luteinizing hormone, and plasma estradiol levels within the postmenopausal range for the study center's laboratory.

* Subject is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study requirements; patient is willing to cooperate in completing quality of life questionnaires during the trial treatment and follow-up period, and agrees that these questionnaire results can be used for clinical research.

Exclusion Criteria:

* Histologically confirmed ovarian cancer of other epithelial origin or non-epithelial origin, other than ovarian clear cell carcinoma; ovarian tumors of low malignant potential (e.g., borderline tumors).
* Prior treatment with immune checkpoint inhibitors (e.g., PD-1/PD-L1 antibodies) or drugs targeting other T-cell receptors (e.g., CTLA-4, etc.), as well as immune checkpoint agonist antibodies (e.g., anti-ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), and immune cell therapy.
* Systemic use of corticosteroids or other immunosuppressive drugs (e.g., cyclophosphamide, azathioprine, methotrexate, thalidomide, TNFα inhibitors, etc.) within 2 weeks before the first dose; Note: Inhaled or topical steroids, steroids as premedication for hypersensitivity reactions (e.g., CT scan contrast agent premedication, cytotoxic chemotherapy premedication), or adrenal replacement steroids (daily ≤10 mg prednisone or equivalent) are permitted in the absence of active autoimmune disease.
* Prior (within 5 years) or concurrent malignancies, with the exception of cured local tumors (e.g., basal cell skin cancer, squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ, etc.) and breast cancer with no recurrence \>3 years after radical surgery.
* Patients with contraindications to bevacizumab, including but not limited to: prior gastrointestinal perforation, surgery within 28 days before medication or incompletely healed wounds, severe bleeding or recent hemoptysis, or other situations where the investigator deems bevacizumab unsuitable.
* Receipt of live vaccine within 30 days before the first dose of study treatment (persisting until 90 days after the last dose of study treatment); Note: Live vaccines include but are not limited to measles, mumps, rubella, varicella/zoster (chickenpox), yellow fever, rabies, BCG, and typhoid vaccines. Seasonal influenza virus vaccines not containing live virus, inactivated COVID-19 vaccines, etc., are permitted.
* Active autoimmune disease requiring systemic treatment (e.g., use of disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years before the first dose. Replacement therapies (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatment; Note: Patients with cataracts, Graves' disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
* Systemic infection requiring systemic antibiotic treatment or other severe infections within 2 weeks before randomization, or unexplained fever \>38.0°C during the screening period or before enrollment, and inability to discontinue aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) for more than 5 days.
* Severe illness or concomitant non-tumor diseases, such as neurological disorders, psychiatric disorders, infectious diseases, or laboratory abnormalities, that may increase the risk of participating in the study or taking study drugs, and which the investigator deems would make the patient unsuitable for the study.
* Pregnant or lactating women.
* Clinically significant cardiovascular diseases, including but not limited to:

  1. Myocardial infarction or unstable angina within 6 months before the first dose.
  2. Stroke or transient ischemic attack within 6 months before the first dose.
  3. Hypertension not controlled by optimal antihypertensive therapy (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg).
  4. Poorly controlled arrhythmias. Patients who have stabilized before the first dose and have been stable for ≥14 days may be enrolled.
  5. Congestive heart failure (New York Heart Association \[NYHA\] functional class II-IV).
  6. Myocarditis.
* Expectation of needing any other form of anti-tumor therapy during the study period.
* Receipt of traditional Chinese medicines with anti-tumor indications or immunomodulatory drugs (including but not limited to thymosin, interferon, interleukin-2, etc.) within 2 weeks before the first dose.
* HIV-positive patients.
* Known history of anti-tuberculosis treatment within one year before the first administration of study treatment.
* Hepatitis B surface antigen (HBsAg) positive and Hepatitis B virus DNA (HBV DNA) ≥2000 IU/ml or 10\&lt;sup\>4\&lt;/sup\> copies/ml; HCV antibody positive and HCV RNA positive.
* Pre-existing peripheral neuropathy of grade ≥2 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
* Current or recent (within 10 days before the first dose of study drug) continuous use of full-dose oral or parenteral anticoagulants or thrombolytic agents for 10 days (Note: Prophylactic use of low-dose anticoagulants is permitted: low-dose warfarin (≤ 1mg/d), low-dose heparin (≤ 12,000 U/d), or low-dose aspirin (≤ 100mg/d) is permitted for prophylactic purposes, provided the prothrombin time International Normalized Ratio (INR) is ≤1.5).
* Hereditary bleeding tendency or coagulation dysfunction, or history of thrombosis, or imaging showing tumor invasion/infiltration of major blood vessels, or investigator or radiologist assessment of bleeding tendency.
* Known history of severe allergy to macromolecular protein preparations, or to any component of QL1706 or other investigational drugs, or severe allergic history to chemotherapeutic drugs such as carboplatin, paclitaxel, or their premedications.
* Currently participating in interventional clinical research treatment, or receiving any other investigational drug or research device treatment within 4 weeks before the first dose (patients who failed screening for other clinical trials may be included in this study).
* Patients deemed unsuitable for participation in this study by the investigator.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to 4 years
Secondary outcomes:
measure: Investigator-assessed PFS
timeFrame: Up to 4 years
measure: Overall Survival (OS)
timeFrame: Up to 4 years
measure: Progression-Free Survival 2 (PFS2)
timeFrame: Up to 4 years
measure: Time to First Subsequent Therapy (TFST)
timeFrame: Up to 4 years
measure: Time to Second Subsequent Therapy (TSST)
timeFrame: Up to 4 years
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Up to 4 years
Other outcomes:
measure: Quality of Life (QoL)
timeFrame: Up to 4 years
measure: Exploratory Biomarker Analysis Endpoint
timeFrame: Up to 4 years
Locations:
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
Study officials:
References: