Cadonilimab Plus Nab -Paclitaxel for Patients With Recurrent, or Metastatic Cervical Cancer Resistant to Immune Checkpoint Inhibitors

NCT05824494 | Not Yet Recruiting Phase 2

• 1 other identifier: AK104-IIT-024
• Study Type: interventional
• Target: 58
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase II trial of combination therapy of cadonilimab(Bispecific Anti-PD-1/CTLA-4 Antibody) plus nab-Paclitaxel in patients with recurrent or metastatic cervical cancer that had failed PD-1/PD-L1 blockade therapy. As a bispecific antibody against PD-1 and CTLA-4, cardonirimab can not only induce the production of a large number of T cells in the early stage of immune response by antagonizing CTLA-4, but also block PD-1 and PD-L1/L2 combination. Thereby restoring the killing function of T cells to tumor cells and reducing the exhaustion of T cells.The hypothesis is the combination of cadonilimab and nab-Paclitaxel will overcome PD-1/PD-L1 blockade-resistance to enhance the response of patients with persistant, recurrent or metastatic cervical cancer.

Conditions

Uterine Cervical Neoplasms; Cancer of Cervix; Cervical Cancer; Cervical Neoplasms; Uterine Cervical Cancer; Cancer of the Uterine Cervix

Keywords

PD-1; immune checkpoint inhibitor

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  To evaluate the clinical activity (as assessed by objective response rate \[ORR\]) of specific Cadonilimab and Nab-Paclitaxel combination.

  up to 2 years

Secondary Outcomes (7)

• Duration of response

  up to 2 years

• Disease control rate (DCR)

  up to 2 years

• Time to response (TTR)

  up to 2 years

• Progression Free survival

  up to 2 years

• Overall survival

  Cycle 1 Day 1, Day 1 of each cycle (each cycle is 21 days), every 12 weeks after end of treatment

Other Outcomes (1)

• Exploratory endpoints

  Within 7 days before treatment, 6 weeks ± 7 days after treatment, 12 weeks ± 7 days after treatment

Study Arms (1)

Cadonilimab plus nab-paclitaxel

EXPERIMENTAL

Drug: Cadonilimab 10mg/kg,every 3 weeks,IV infusion Drug: Nab paclitaxel ≤260mg/m2,every 3 weeks,IV infusion

Drug: Cadonilimab; Drug: Nab paclitaxel

Interventions

Cadonilimab DRUG

Cadonilimab 10mg/kg,every 3 weeks,IV infusion

Cadonilimab plus nab-paclitaxel

Nab paclitaxel DRUG

Nab paclitaxel ≤260mg/m2,every 3 weeks,IV infusion

Cadonilimab plus nab-paclitaxel

Eligibility Criteria

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

You may qualify if:

• Subjects are autonomous and fully autonomous, understand and voluntarily sign a written informed consent within 30 days before enrollment.
• Age ≥ 18 and ≤ 75 years old on the date of signing the informed consent form, female.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Expected survival period ≥ 3 months.
• Persistent, recurrent or metastatic cervical cancer confirmed by histology or cytology.
• Subjects who have previously failed treatment with PD-1, PD-L1 or CTLA4 inhibitors.
• There is at least one measurable tumor lesion according to the RECIST v1.1 standard; tumor lesions in the previous radiotherapy area or other locoregional treatment sites are generally not regarded as measurable lesions, unless the lesion has definite progression and persists after 3 months of radiotherapy, Or the tumor nature of the lesion is confirmed by biopsy.
• All subjects need to provide informed consent to provide freshly obtained tumor tissue samples or tumor tissue samples archived within 5 years (formalin-fixed paraffin-embedded \[FFPE\] tissue wax blocks or at least 5 unstained tumor tissue Biopsy samples, preferably freshly obtained tumor tissue samples). If the subject cannot provide the tumor tissue sample archived within 5 years before randomization or the tumor tissue sample is not suitable for use, a biopsy must be performed to collect fresh tumor tissue; if the investigator judges that there is a safety risk in the subject's tumor tissue biopsy, the Discuss with medical monitor.
• The subject agrees to collect tumor tissue and peripheral blood samples required during the screening period and the research process and apply them to relevant research.
• The results of laboratory tests after the screening period suggest that the subject has good organ function:
• Hematology (no blood components and cell growth factor supportive treatment are allowed within 2 weeks before randomization): i. The absolute value of neutrophils ANC ≥ 1.5 × 109/L (1,500/mm3); ii. Platelet count ≥ 100 × 109/L (100,000/mm3); iii. Hemoglobin ≥ 90 g/L.
• Kidneys: i. Calculated creatinine clearance\* (CrCl) ≥ 50 mL/min
• \* CrCl will be calculated using the Cockcroft-Gault formula (Cockcroft-Gault formula) CrCl (mL/min) = {(140 - age) × body weight (kg) × 0.85}/ (serum creatinine. (mg/dL) × 72) ii. Urinary protein \< 2+ or 24-hour (h) urine protein quantitative \< 1.0 g.
• Liver: i. Serum total bilirubin (TBil) ≤ 1.5 × ULN ii. AST and ALT ≤ 2.5× ULN iii. Serum albumin (ALB) ≥ 28 g/L
• coagulation function: i. International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (if the subject is receiving anticoagulant therapy, the subject must receive a stable dose of anticoagulant and coagulation parameters at the time of screening (PT/INR and APTT) were within expected ranges with anticoagulant therapy).

You may not qualify if:

• Suffering from other active malignant tumors within 3 years before randomization, except locally curable tumor types and those who have been cured, such as Squamous cell carcinoma of the skin, basal cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the breast.
• Severe immunotherapy-related toxicity occurred during the previous anti-PD-1/PD-L1 monoclonal antibody treatment, including but not limited to: grade 3/4 pneumonia, proteinuria, uveitis or episcleritis, myasthenia gravis, Pancreatitis, hepatitis, bullous skin disease (including SJS, TEN); grade 2-4 encephalitis, myocarditis; any grade of Guillain-Barré syndrome, transverse myelitis; severe inflammation that significantly affects the quality of life of the patient sex joints.
• Received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, or other unmarketed clinical research drugs and other anti-tumor treatments within 4 weeks before the first use of the study drug.
• Received nab-paclitaxel drug therapy within 6 months before the first use of the study drug. Known contraindications to nab-paclitaxel or hypersensitivity to any of its components.
• Received drugs with immunomodulatory effects (such as thymosin, interferon, interleukin-2) within 2 weeks before randomization; received Chinese patent medicines with anti-tumor indications (such as Aidi injection, etc.) within 2 weeks before randomization.
• Received major organ surgery (not including needle biopsy, etc.) or experienced significant trauma within 4 weeks before the first use of the study drug, or required elective surgery during the trial
• There is central nervous system metastasis or cancerous meningitis.
• Pleural effusion, pericardial effusion, or peritoneal effusion with uncontrollable need for repeated drainage (more than once a month) of subjects.
• Suffering from active or recurrent autoimmune diseases; except the following: vitiligo, alopecia, psoriasis, or eczema that do not require systemic treatment; hypothyroidism caused by autoimmune thyroiditis that only requires stable doses of Hormone replacement therapy; type 1 diabetes requiring only a steady dose of insulin replacement therapy.
• Subjects who need to use \> 10 mg/day prednisone or equivalent dose of glucocorticoid or other immunosuppressive drugs for systemic treatment within 14 days before randomization; except the following
• Inhaled, ophthalmic or topical glucocorticoid therapy with a dose of ≤ 10 mg/day prednisone or equivalent dose is allowed.
• Physiological glucocorticoid replacement therapy, with a dose of ≤ 10 mg/day prednisone or an equivalent dose of glucocorticoid.
• Glucocorticoids as prophylaxis for hypersensitivity reactions (eg, before CT examination).
• Live vaccines have been used within 4 weeks before randomization.
• Known primary or secondary immunodeficiency, including human immunodeficiency virus (HIV) antibody test positive.

Sponsors & Collaborators

• Women's Hospital School Of Medicine Zhejiang University: lead
• Akeso: collaborator

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Taxes

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations

Study Officials

• hui Wang, PHD

  Women's Hospital School Of Medicine Zhejiang University

  PRINCIPAL INVESTIGATOR

• bairong xia, PHD

  Anhui Provincial Cancer Hospital

  PRINCIPAL INVESTIGATOR

• Ge Lou, PHD

  The Second Affiliated Hospital of Harbin Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

hui Wang, PHD

CONTACT

0086-571-87061501; wang71hui@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: cadonilimab 10mg/kg Q3W and nab-paclitaxel ≤260mg/m2 Q3W

Study Record Dates

• First Submitted: April 9, 2023
• First Posted: April 21, 2023
• Study Start: June 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 6, 2023

Record last verified: 2023-05