Combining Cadonilimab with chemotherapy for advanced cervical cancer

Induction Chemotherapy Plus Cadonilimab Followed by Chemoradiotherapy for Locally Advanced Cervical Cancer: A Multicenter, Open-label, Single-arm, Phase II Trial

This study tests if combining a new drug called Cadonilimab with chemotherapy can help people with advanced cervical cancer feel better and respond to treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Academic / other)
• Drugs / interventions: prednisone, Cadonilimab, chemotherapy, immunotherapy, radiation
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06511726 on ClinicalTrials.gov

What this trial studies

This Phase II clinical study evaluates the efficacy, safety, and tolerability of Cadonilimab in combination with chemotherapy as induction therapy for patients with locally advanced cervical cancer. The study aims to explore the correlation between PD-L1 expression in tumor samples and immune-related factors during treatment. It is structured in two stages, starting with 9 patients, and will proceed based on the number of effective cases observed. The treatment regimen includes Cadonilimab, cisplatin, and albumin-bound paclitaxel, followed by radiotherapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed locally advanced cervical cancer and measurable lesions.

Not a fit: Patients with distant metastasis or other histological types of cervical cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with locally advanced cervical cancer.

How similar studies have performed: Other studies have shown promise in using immunotherapy combined with chemotherapy for various cancers, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

1. Patients with good compliance.
2. Age ≥ 18 years (calculated on the day of signing the informed consent).
3. Histologically or pathologically diagnosed with cervical cancer (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma) and measurable lesions.
4. Initial diagnosis of stage IB3-IVA (according to FIGO 2018 staging).
5. ECOG performance score of 0-2.
6. Main organ functions meet the protocol criteria within 7 days before treatment.

Exclusion Criteria:

1. Patients with other histological types of cervical cancer, such as neuroendocrine carcinoma or sarcoma.
2. Evidence of distant metastasis, including groin lymph node metastasis and lymph node metastasis above the L1 level.
3. Previously underwent total hysterectomy (removal of the uterus body + cervix). History of subtotal hysterectomy or cervical wedge resection that preserves the cervix is allowed.
4. With anatomical abnormalities or tumor geometry-related contraindications that prevent the use of brachytherapy.
5. Within 2 years, had other active malignant tumors, except for locally curable tumors that have been cured, such as squamous cell carcinoma of the skin, basal cell carcinoma of the skin, superficial bladder cancer, and ductal carcinoma in situ of the breast.
6. With clinically significant bilateral hydronephrosis that, in the investigator's judgment, cannot be relieved by nephrostomy or ureteral stent placement.
7. Previously received immune checkpoint inhibitors (e.g., anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-CTLA-4 antibodies) or any treatment targeting tumor immune mechanisms involving immune co-stimulatory factors (e.g., antibodies targeting ICOS, CD40, CD137, GITR, OX40).
8. Within 2 weeks, requires the use of glucocorticoids (\> 10 mg/day prednisone or equivalent dose of glucocorticoids) or other immunosuppressive drugs for systemic treatment exceptions include: a) Allowed treatment with inhaled, ophthalmic, or local doses ≤ 10 mg/day prednisone or equivalent dose of glucocorticoids. b) Physiological glucocorticoid replacement therapy at a dose ≤ 10 mg/day prednisone or equivalent dose of glucocorticoids. c) Glucocorticoids used for prophylaxis against hypersensitivity reactions (e.g., premedication for CT scans).
9. Within 2 weeks, received drugs with immunomodulatory effects (e.g., thymosin, interferon, interleukin-2).
10. Presence of active systemic infections requiring systemic treatment (including active pulmonary tuberculosis, active syphilis caused by Treponema pallidum, and fungal infections requiring systemic treatment) note: exclusion does not apply to antiviral drugs used for hepatitis B virus infection.
11. Within 4 weeks, experienced severe infections, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia.
12. Within 4 weeks, underwent major surgical treatment (as determined by the investigator), open biopsy, or significant trauma or requires scheduled major surgical treatment during the study. Diagnostic systematic pelvic/aortic lymphadenectomy is allowed.
13. Received live vaccines within 4 weeks .
14. With active or history of documented autoimmune diseases exceptions include: vitiligo, alopecia, psoriasis, or eczema that do not require systemic treatment hypothyroidism caused by autoimmune thyroiditis requiring stable dose of hormone replacement therapy type 1 diabetes requiring stable dose of insulin replacement therapy.
15. Any of the following cardiovascular diseases: a) New York Heart Association (NYHA) functional classification ≥ II for heart failure. b) Presence of severe arrhythmias requiring long-term drug intervention asymptomatic patients with stable ventricular rate in atrial fibrillation are allowed to enroll. c) Occurrence of cerebrovascular events (CVA) within 6 months . d) Left ventricular ejection fraction (LVEF) \< 50%.
16. Known primary or secondary immunodeficiency, including positive human immunodeficiency virus (HIV) antibody test.
17. Subjects with active hepatitis B virus (HBV) infection, non-active or asymptomatic carriers of hepatitis B surface antigen (HBsAg) with HBV DNA \> 1000 IU/mL, and subjects with active hepatitis C virus (HCV) infection. Note: Non-active or asymptomatic carriers with treated and stable hepatitis B infection with HBV DNA ≤ 1000 IU/mL are allowed to enroll. Subjects with cured hepatitis C infection, positive HCV antibody (HCVAb), and negative HCV RNA are allowed to enroll.
18. With active or documented history of inflammatory bowel disease (such as Crohn's disease, ulcerative colitis) or active diverticulitis.
19. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
20. Known history of severe hypersensitivity reactions to other monoclonal antibodies.
21. Pregnant or breastfeeding women.
22. The investigator believes that there may be risks associated With receiving the investigational drug or any condition that may interfere With the evaluation of the investigational drug, subject safety, or interpretation of study results (such as having other severe diseases or mental disorders).

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen Memorial hosipital — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Shoumin Bai — Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Study coordinator: Lin Ding

Conditions Cervical Cancer; cervical cancer; immunotherapy; Induction chemotherapy; Cadonilimab