Cadonilimab Plus Chemotherapy in LACC: A Prospective, Multicenter, Randomized Phase II Trial

• Neoadjuvant Therapy Plus Surgery (Procedure): Patients received three cycles of neoadjuvant cadonilimab plus chemotherapy. Patients subsequently underwent radical hysterectomy with pelvic lymphadenectomy, with para-aortic lymph node biopsy/dissection performed when indicated. Postoperative adjuvant therapy was administered according to pathological findings.
• Concurrent Chemoradiotherapy (Procedure): Patients received standard concurrent chemoradiotherapy (CCRT), consisting of external beam radiotherapy combined with concurrent platinum-based chemotherapy.

Primary outcomes

• 2-year progression-free survival (PFS) rate [2 years after randomization]: The proportion of patients who remain alive without radiologically confirmed disease progression at 2 years after randomization. Disease progression will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on imaging evaluations.

Sex: Female, ages: 18 Years to 75 Years

Inclusion Criteria:

1. Patients with previously untreated locally advanced cervical cancer, clinically staged as FIGO 2018 stage IB3, IIA2, IIB, or IIIC1r (tumor diameter >4 cm as assessed by contrast-enhanced pelvic MRI);
2. Histologically or cytologically confirmed cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma;
3. Female patients aged ≥18 and ≤75 years;
4. Willing and able to provide written informed consent and comply with study visits and protocol-required procedures;
5. Eligible for radical hysterectomy with curative intent;
6. At least one measurable lesion according to RECIST version 1.1;
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
8. Estimated life expectancy of at least 6 months;
9. Women of childbearing potential must agree to use effective contraception throughout the study period. A negative serum or urine pregnancy test is required before study enrollment.

Exclusion Criteria:

1. Histological subtypes other than squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma, including but not limited to small cell carcinoma and clear cell carcinoma.
2. Clinically significant unrecoverable hydronephrosis;
3. CNS metastases or leptomeningeal disease;
4. Active malignancy within 3 years prior to enrollment (with specified exceptions);
5. Prior exposure to immune checkpoint inhibitors or other immunomodulatory anticancer therapies;
6. Major surgery within 4 weeks before study treatment;
7. Severe cardiovascular or cerebrovascular disease;
8. Unresolved toxicities from previous anticancer therapy (> Grade 1, CTCAE v5.0);
9. Known hypersensitivity to study drugs;
10. Serious medical or psychiatric conditions that may interfere with study participation;
11. Pregnancy.