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

NCT07002346 | 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 phase 3 clinical trial is to evaluate whether QL1706 plus bevacizumab can effectively treat adult female patients (18 to \<75 years old) with newly diagnosed FIGO stage IC-IV ovarian clear cell carcinoma. The main questions it aims to answer are:

1. 1.Does QL1706 plus bevacizumab, compared with standard platinum-based chemotherapy with or without bevacizumab, prolong patients' progression-free survival (PFS)?
2. 2.What is the safety profile of QL1706 followed by QL1706 plus bevacizumab, such as what medical problems (adverse events) do participants experience?
3. 3.Be randomly assigned to receive either QL1706 alone during Cycle 1 followed by QL1706 plus bevacizumab from Cycle 2, or paclitaxel plus carboplatin with or without bevacizumab according to prespecified high-risk criteria.
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 randomization to the first documented radiographic disease progression according to RECIST v1.1 as assessed by blinded independent central review (BICR), or death from any cause, whichever occurs first.

  Up to 4 years

Secondary Outcomes (5)

• 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

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  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 CTLA-4); Drug: Bevacizumab

Control Arm: Paclitaxel + Carboplatin ± Bevacizumab

ACTIVE COMPARATOR

Paclitaxel 175 mg/m² Q3W (D1) + Carboplatin AUC 5 Q3W (D1), for 6 cycles, with or without Bevacizumab 15 mg/kg Q3W (D1) according to prespecified high-risk criteria. Bevacizumab may be continued until disease progression, unacceptable toxicity, or completion of a maximum of 22 cycles.

Drug: Bevacizumab; Drug: carboplatin; Drug: Paclitaxel

Interventions

Bevacizumab DRUG

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

Control Arm: Paclitaxel + Carboplatin ± Bevacizumab; 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 ± Bevacizumab

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 ± Bevacizumab

QL1706 (bispecific antibody targeting PD-1 and CTLA-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

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 are planned to undergo primary debulking surgery (PDS), regardless of whether satisfactory debulking is achieved, and have complete surgical records and residual disease assessment results (R0 vs R1/R2).
• No prior first-line postoperative systemic antitumor therapy for the current ovarian clear cell carcinoma, including chemotherapy, targeted therapy, immunotherapy, etc.
• 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) ≥ 1.5 × 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 and SCr = serum creatinine.
• ii. Urine protein \< 2+ or 24-hour quantitative urine protein \< 1.0 g.
• Hepatic:
• i. Total serum bilirubin (TBil) ≤ 1.5 × ULN. ii. AST and ALT ≤ 2.5 × ULN.

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, such as borderline tumors.
• Prior systemic preoperative antitumor therapy for the current ovarian clear cell carcinoma, including but not limited to neoadjuvant chemotherapy (NACT) or other types of neoadjuvant therapy, or planned neoadjuvant therapy followed by interval debulking surgery (IDS) during screening.
• Prior treatment with immune checkpoint inhibitors, such as PD-1/PD-L1 antibodies, or drugs targeting other T-cell receptors, such as CTLA-4, as well as immune checkpoint agonist antibodies, such as anti-ICOS, CD40, CD137, GITR, or OX40 antibodies, and immune cell therapy.
• Systemic use of corticosteroids or other immunosuppressive drugs, such as cyclophosphamide, azathioprine, methotrexate, thalidomide, or TNFα inhibitors, within 2 weeks before the first dose. Note: Inhaled or topical steroids, steroids as premedication for hypersensitivity reactions, such as CT scan contrast agent premedication or 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, such as 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, 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, such as use of disease-modifying drugs, corticosteroids, or immunosuppressants, within 2 years before the first dose. Replacement therapies, such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency, 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, defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg.

Sponsors & Collaborators

• Tongji Hospital: lead
• Chinese Academy of Medical Sciences: collaborator
• Peking Union Medical College Hospital: collaborator
• Fudan University: 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
• 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
• 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
• The International Peace Maternity & Child Health Hospital of China welfare institute: collaborator
• Sun Yat-Sen University Cancer Center: collaborator
• Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center: collaborator

Study Sites (1)

Tongji Hospital

Wuhan, Hubei, 430000, China

RECRUITING

MeSH Terms

Interventions

CTLA-4 Antigen; Bevacizumab; Carboplatin; Paclitaxel

Intervention Hierarchy (Ancestors)

Immune Checkpoint Proteins; Proteins; Amino Acids, Peptides, and Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood 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: November 15, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2029
• Last Updated: May 18, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)