INVIGORATE: A Study of QL1706 and Bevacizumab in Advanced First-Line Ovarian Clear Cell Carcinoma

NCT07002346 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 2025-TJ-OCCC
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 1

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. 1.Does QL1706 combined with bevacizumab, compared to platinum-based chemotherapy, prolong patients' progression-free survival (PFS)?
2. 2.What is the safety profile of QL1706 combined with bevacizumab, such as what medical problems (adverse events) do participants experience?
3. 3.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).
4. 4.Visit the research center regularly for drug infusions, medical examinations (such as vital signs, physical exams, laboratory tests), and tumor imaging assessments.
5. 5.Complete quality of life questionnaires as required.

Conditions

Ovarian Clear Cell Carcinoma

Keywords

Ovarian Clear Cell Carcinoma; QL1706; Bevacizumab; First-line treatment; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is defined as the time from enrollment to the first imaging disease progression or death (whichever occurs first). Assessed according to RECIST v1.1 by BICR.

  Up to 4 years

Secondary Outcomes (6)

• Investigator-assessed PFS

  Up to 4 years

• Overall Survival (OS)

  Up to 4 years

• Progression-Free Survival 2 (PFS2)

  Up to 4 years

• Time to First Subsequent Therapy (TFST)

  Up to 4 years

• Time to Second Subsequent Therapy (TSST)

  Up to 4 years

Other Outcomes (2)

• Quality of Life (QoL)

  Up to 4 years

• Exploratory Biomarker Analysis Endpoint

  Up to 4 years

Study Arms (2)

Experimental Arm: QL1706 + Bevacizumab

EXPERIMENTAL

QL1706 5 mg/kg Q3W (D1)+Bevacizumab 15mg/kg Q3W (D1) (QL1706/Bevacizumab treatment for a maximum of 2 years/22 cycles)

Drug: QL1706 (bispecific antibody targeting PD-1 and CLTA-4); Drug: Bevacizumab

Control Arm: Paclitaxel +Carboplatin

ACTIVE COMPARATOR

Paclitaxel 175 mg/m2 Q3W (D1)+Carboplatin (AUC=5) Q3W (D1), 6 cycles

Drug: carboplatin; Drug: Paclitaxel

Interventions

QL1706 (bispecific antibody targeting PD-1 and CLTA-4) DRUG

QL1706: 5 mg/kg intravenously every 3 weeks until disease progression or intolerable toxicity, with a maximum duration of 2 years.

Experimental Arm: QL1706 + Bevacizumab

Bevacizumab DRUG

Bevacizumab : 15 mg/kg intravenously every 3 weeks until disease progression or intolerable toxicity, with a maximum duration of 22 cycles.

Experimental Arm: QL1706 + Bevacizumab

carboplatin DRUG

Carboplatin: AUC=5, intravenously every 3 weeks until disease progression or intolerable toxicity, with a maximum duration of 6 cycles

Control Arm: Paclitaxel +Carboplatin

Paclitaxel DRUG

Paclitaxel: 175 mg/m\^2 intravenously every 3 weeks until disease progression or intolerable toxicity, with a maximum duration of 6 cycles

Control Arm: Paclitaxel +Carboplatin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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:
• Myocardial infarction or unstable angina within 6 months before the first dose.
• Stroke or transient ischemic attack within 6 months before the first dose.
• Hypertension not controlled by optimal antihypertensive therapy (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg).
• Poorly controlled arrhythmias. Patients who have stabilized before the first dose and have been stable for ≥14 days may be enrolled.

Sponsors & Collaborators

• Tongji Hospital: lead
• Chinese Academy of Medical Sciences: collaborator
• Peking Union Medical College Hospital: collaborator
• Fudan University: collaborator
• Sun Yat-sen University Cancer Center (SUSUCC): collaborator
• Peking University Cancer Hospital & Institute: collaborator
• Peking University People's Hospital: collaborator
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• The Second Affiliated Hospital, Sun Yat-sen University: collaborator
• Second Affiliated Hospital, School of Medicine, Zhejiang University: collaborator
• Renmin Hospital of Wuhan University: collaborator
• Zhejiang Provincial People's Hospital: collaborator
• Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center: collaborator
• Shanghai First Maternity and Infant Hospital: collaborator
• Hubei Cancer Hospital: collaborator
• Sir Run Run Shaw Hospital: collaborator
• Wuhan Central Hospital: collaborator
• Zhejiang Cancer Hospital: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator
• Third Affiliated Hospital of Zhengzhou University: collaborator
• Henan Provincial People's Hospital: collaborator
• Henan Cancer Hospital: collaborator
• Jiangsu Cancer Institute & Hospital: collaborator
• The International Peace Maternity & Child Health Hospital of China welfare institute: collaborator
• Women's Hospital School Of Medicine Zhejiang University: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• First Affiliated Hospital of Zhejiang University: collaborator

Study Sites (1)

Tongji Hospital

Wuhan, Hubei, 430000, China

Location

MeSH Terms

Interventions

Bevacizumab; Carboplatin; Paclitaxel

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 20, 2025
• First Posted: June 3, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2029
• Last Updated: June 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)