Induction Immunotherapy Combined With Chemotherapy Followed by Concurrent Chemoradiotherap and Immunotherapy for Cervical Cancer

Induction Immunotherapy Combined With Chemotherapy Followed by Concurrent Chemoradiotherap and Immunotherapy for Advanced Cervical Cancer: An Open-Label, Single-Arm, Phase II Trial

To explore the efficacy and tolerability of a platinum-based regimen combined with the PD-1 antibody toripalimab administered prior to concurrent chemoradiotherapy in patients with locally advanced cervical cancer.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: Toripalimab; Radiation: Pelvic External-Beam Radiotherapy (EBRT)

Detailed Description

At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, investigators reported that neoadjuvant camrelizumab combined with induction chemotherapy, followed by camrelizumab plus concurrent chemoradiotherapy and subsequent camrelizumab maintenance, achieved an overall response rate of 100 % in patients with locally advanced cervical cancer, with an acceptable safety profile.

Pre-clinical studies have suggested that concurrent chemoradiotherapy may dampen immune activation in cervical cancer, including reductions in the CD4+/CD8+ T-cell ratio and decreased T-cell receptor (TCR) diversity. These findings imply that administration of immunotherapy prior to chemoradiotherapy might be more effective than giving it concomitantly or afterwards.

Informed by these clinical and translational data, we propose to conduct an initial, prospective phase II trial to evaluate the efficacy and safety of neoadjuvant chemo-immunotherapy followed by concurrent chemoradiotherapy plus immunotherapy in patients with locally advanced cervical cancer, thereby laying the groundwork for a subsequent phase III investigation.

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jie Chen; Phone Number: +86-18622221202; Email: tjcjvip@126.com
• Study Contact Backup: Name: Yuanjie Cao; Phone Number: +86-18522123151; Email: cyjro325@gmail.com

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Tianjin Medical University Cancer Institute&Hospital
    • Contact: Jie Chen; Phone Number: +8618622221202; Email: tjcjvip@126.com
    • Contact: Yuanjie Cao; Phone Number: +86-15510932601; Email: cyjro325@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women aged 18-75 years.

  • Histologically confirmed, previously untreated locally advanced cervical cancer of squamous, adenocarcinoma, or adenosquamous type.
  • At least one measurable lesion that has not received prior local therapy (non-nodal lesion ≥ 10 mm longest diameter or pathological lymph node ≥ 15 mm short axis, per RECIST 1.1).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
  • Estimated life expectancy ≥ 6 months.
  • Investigator-assessed eligibility for concurrent chemoradiotherapy.
  • No clinically significant active bleeding.
  • Laboratory values: WBC > 4 × 10⁹/L; platelets > 100 × 10⁹/L.
  • No history of other malignancies.
  • Women of child-bearing potential must have a negative serum pregnancy test and use effective contraception throughout the study.
  • Written informed consent obtained prior to any study-related procedures.

Exclusion Criteria:

• Tumor recurrence or distant metastasis at screening.

  • Active autoimmune disease requiring systemic therapy, or any chronic condition requiring long-term high-dose corticosteroids (≥10 mg/day prednisone or equivalent) or other immunosuppressive agents.
  • Systemic corticosteroids (>10 mg/day prednisone or equivalent) or any other immunosuppressive drugs within 14 days before first study dose or anticipated during the study.
  • Live-attenuated vaccination within 30 days before first dose or planned during the study.
  • Prior organ transplantation or known HIV infection.
  • Active hepatitis B (HBV DNA >2000 IU/mL or >10⁴ copies/mL, or HBsAg positive) or active hepatitis C (HCV RNA >10³ copies/mL); co-infection with both viruses is also excluded.
  • Prior therapy with any agent targeting PD-1, PD-L1, PD-L2, CD137, CTLA-4 (e.g., ipilimumab), or any other antibody or drug that modulates T-cell co-stimulation or checkpoint pathways.
  • Known hypersensitivity to monoclonal antibodies, fusion proteins, or any excipients in the investigational products.
  • History of another malignancy within the past 5 years, except adequately treated cervical carcinoma in situ, basal-cell carcinoma of the skin, or other localized malignancies considered cured.
  • Severe non-surgical comorbidity or acute infection.
  • Peripheral neuropathy > Grade 1 (NCI-CTCAE).
  • Inadequate hematologic or organ function:
  • WBC < 4.0 × 10⁹/L, ANC < 1.5 × 10⁹/L, platelets < 100 × 10⁹/L, Hb < 90 g/L
  • TBIL > 1.5 × ULN, ALT/AST > 2.5 × ULN, BUN > 1.5 × ULN, creatinine > 1.5 × ULN
  • Symptomatic brain metastases.
  • Clinically significant cardiac arrhythmias, myocardial ischemia, severe conduction block, heart failure, or severe valvular disease.
  • Severe bone-marrow failure.
  • Uncontrolled psychiatric illness.
  • Pregnant or lactating women.
  • Investigator-judged unsuitability for the trial.
  • Concurrent participation in another interventional clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PD-1 arm; Induction PD-1 inhibitor followed by PD-1 maintenance administered concurrently with chemoradiotherapy and continued after completion.

Drug: Toripalimab; Induction chemo-immunotherapy (platinum-based tri-weekly regimen); Paclitaxel 175 mg/m² IV on day 1; Cisplatin 50 mg/m² IV on day 1 or carboplatin AUC 4-5 IV on day 1; Toripalimab 240 mg IV on day 1, administered immediately before each chemotherapy infusion Cycle length: every 3 weeks Number of cycles: 2 Concurrent chemoradiotherapy (weekly regimen); Radiation therapy delivered according to institutional protocol; Cisplatin 40 mg/m² IV once weekly; Toripalimab 240 mg IV on day 1 of every 3-week cycle, given before chemotherapy Cycle length: every 3 weeks during radiotherapy Maintenance immunotherapy • Toripalimab 240 mg IV on day 1 every 3 weeks (Q3W) Duration: 1 year (total 13 cycles); Radiation: Pelvic External-Beam Radiotherapy (EBRT); PTV: 6 MV photons, 1.80 Gy per fraction × 28 fractions = 50.4 Gy.; PGTVnd: 6 MV photons, 2.14 Gy per fraction × 28 fractions = 59.92 Gy. Brachytherapy:Dose prescriptions; Dose: 7.00 Gy per fraction × 4 fractions = 28.0 Gy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	The proportion of patients with at least one tumor scan of complete response (CR) or partial response (PR) using RECIST v1.1	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival	Time from diagnosis of disease to disease recurrence or death due to any cause	3 year
Overall survival	Time from diagnosis of disease of treatment until death due to any cause	3 year

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 16, 2025
• First Submitted That Met QC Criteria: July 29, 2025
• First Posted (Actual): July 30, 2025

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms
• Other Study ID Numbers: E20250419

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No