A Phase II Study of Utidelone With Toripalimab in Advanced Cervical Cancer

Utidelone Combined With Toripalimab in Patients With Pretreated Recurrent or Metastatic Cervical Cancers: a Single-Arm, Phase II Study

This is a Phase II clinical trial to evaluate the safety and efficacy of Utidelone, a genetically engineered epothilone derivative, combined with Toripalimab, a PD-1 inhibitor, in patients with recurrent or metastatic cervical cancer who have progressed after standard treatments. The study will also assess the safety profile of this combination therapy. The primary objectives of this study include: (1) to determine the objective response rate (ORR), meaning whether the treatment can reduce the size of tumors or make them disappear, according to the RECIST 1.1 criteria; (2) to evaluate the safety of the treatment and document the side effects experienced by participants. This study is for individuals who: (1) are between 18 and 75 years old; (2) have a confirmed diagnosis of recurrent or metastatic cervical cancer; (3) have previously received at least one standard chemotherapy regimen that is no longer controlling the cancer; (4) are in generally good health, as determined by the study investigators. In this single-arm study, all participants will receive the same treatment: Utidelone will be administered by intravenous (IV) infusion over 1.5 hours, once a day for 5 consecutive days, in each 21-day treatment cycle; Toripalimab will be administered by IV infusion over 1.5 hours, once on Day 6 of each 21-day cycle. Participants may continue receiving the study drugs as long as they are benefiting from the treatment and side effects are manageable. Doctors will assess tumor size using imaging scans (like CT or MRI) every 6 weeks to monitor how the cancer responds to treatment. The study will take place at Zhongnan Hospital of Wuhan University and plans to include approximately 32 participants.

Inclusion Criteria:

1. Informed Consent: Patients must voluntarily sign an informed consent form prior to any study-related procedures.

2. Age: Aged ≥18 years and ≤75 years.

3. Diagnosis: Histologically or cytologically confirmed recurrent or metastatic cervical carcinoma.

4. Performance Status: With an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

5. Measurable Disease: With at least one measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

6. Prior Therapy:

   • Patients must have received at least one line of standard systemic chemotherapy for recurrent/metastatic disease, OR
   • Patients with rapid disease progression (occurring within 6 months) during or after prior neoadjuvant or concurrent chemoradiotherapy.

7. Treatment-Related Toxicity: Recovery from all toxicities related to prior anti-cancer therapies to ≤ Grade 1 (according to CTCAE v5.0). Patients with alopecia of any grade are eligible.

8. Adequate Hematological Function (within 1 week prior to enrollment, per local laboratory reference ranges):

   • White blood cell count (WBC) ≥ 2.5 × 10⁹/L.
   • Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L.
   • Platelet count (PLT) ≥ 100 × 10⁹/L.
   • Hemoglobin (Hb) ≥ 9.0 g/dL (transfusion or erythropoietin use is permitted to meet this criterion).

9. Adequate Liver and Kidney Functions (within 1 week prior to enrollment, per local laboratory reference ranges):

   • Total bilirubin (TBIL) ≤ 1.5 × the upper limit of normal (ULN).
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases).
   • Calculated creatinine clearance (Ccr) ≥ 60 mL/min.

10. Contraception: Patients of childbearing potential must agree to use highly effective contraception during the study and for at least 90 days after the last dose of study treatment. A negative serum or urine pregnancy test is required for female patients of childbearing potential within 7 days prior to enrollment.

11. Life Expectancy: Anticipated life expectancy of at least 12 weeks.

12. Compliance: Patients must be able and willing to comply with the study protocol for treatment and follow-up.

Exclusion Criteria:

1. Concurrent Malignancy: History of other active malignancies within the past 5 years, except for adequately treated basal cell carcinoma of the skin.

2. Recent Anti-cancer Therapy: Any anti-cancer therapy (including chemotherapy, radical radiotherapy, hormonal therapy, biological therapy, or anti-cancer Chinese herbal medicine) within 4 weeks prior to the initiation of study treatment.

3. Recent Major Surgery/Trauma: Major surgical procedure (excluding diagnostic biopsy) or significant traumatic injury within 4 weeks prior to the first dose of study drug, or anticipation of the need for major surgery during the study period.

4. Prior Neurotoxicity: History of ≥ Grade 3 neurological adverse reactions attributed to prior anti-microtubule therapy.

5. Symptomatic CNS Metastases: Patients with symptomatic central nervous system (CNS) metastases.

6. Pregnancy/Lactation: Women who are pregnant or breastfeeding.

7. Hypersensitivity: Known or suspected hypersensitivity to any component of the study drugs or their excipients.

8. Severe Comorbidities: Any uncontrolled or severe concurrent medical condition that, in the investigator's judgment, would preclude participation, including but not limited to:

   • Severe cardiovascular or cerebrovascular disease.
   • Uncontrolled diabetes mellitus or hypertension.
   • Active severe infection.
   • Active peptic ulcer disease.
   • Uncontrolled psychiatric illness/disorder.

9. General Exclusion: Any other condition or circumstance that, in the opinion of the investigator, would compromise the patient's safety or compliance, or make the patient unsuitable for study participation.

10. Contraindication to Steroids: Conditions for which corticosteroid use is contraindicated.