Neoadjuvant immunochemotherapy for PD-L1-negative locally advanced cervical cancer

Neoadjuvant Chemotherapy Plus Camrelizumab in PD-L1-negative Locally Advanced Cervical Cancer: a Multicentre, Single-arm, Phase 2 Trial

This study is testing a new treatment that combines chemotherapy with a drug called Camrelizumab to see if it can help people with PD-L1-negative locally advanced cervical cancer before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Tongji Hospital (Academic / other)
• Drugs / interventions: immunotherapy, prednisone, Camrelizumab, chemotherapy
• Locations: 12 sites (Hefei, Anhui and 11 other locations)
• Trial ID: NCT06288360 on ClinicalTrials.gov

What this trial studies

This multicenter, prospective, single-arm clinical trial aims to evaluate the efficacy of combining neoadjuvant chemotherapy with the PD-1 inhibitor Camrelizumab in patients with PD-L1-negative locally advanced cervical cancer. Participants will receive an initial course of chemotherapy followed by two courses of immunochemotherapy. The study will assess tumor remission rates, surgical complications, positive margin rates, and overall patient survival. Additionally, it will explore changes in local immune factors and tumor cells during treatment and identify potential biomarkers for treatment efficacy.

Who should consider this trial

Good fit: Ideal candidates include patients aged 18-70 with FIGO stage IB3, IIA2, or IIB/IIIC1r cervical cancer who have not received prior treatment and have measurable lesions.

Not a fit: Patients with PD-L1-positive tumors or those with advanced disease stages beyond the specified criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and survival rates for patients with PD-L1-negative locally advanced cervical cancer.

How similar studies have performed: Other studies have shown promising results with similar neoadjuvant immunotherapy approaches, although this specific combination is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. FIGO 2018 stage IB3, IIA2, or IIB/IIIC1r (tumor size\>4cm) cervical cancer and without any treatment (After undergoing gynecological examinations by two associate chief physicians or above, the staging of the patients was determined);
2. Has at least one measurable lesion based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. In principle, the size of the lesion as shown by the magnetic resonance imaging examination is used as the criterion.
3. Histologically confirmed squamous carcinoma, adenocarcinoma (common type) or adenosquamous carcinoma of the cervix;
4. Negative PD-L1 expression on preoperative pathological examination (Combined positive score \< 1);
5. 18-70 years of age;
6. Eastern Cooperative Oncology Group score ≤ 1;
7. WBC≥3.5\*10\^9/L, NEU≥1.5\*10\^9/L, Platelet≥100×10\^9 /L; AST and ALT ≤1.5 times normal upper limit; Total bilirubin ≤1.5 times the upper limit of normal value; serum creatinine and blood urea nitrogen ≤the upper limit of normal value;
8. Well-compliance and willing to keep in touch;
9. Willing to participate in this study, sign the informed consent, and comply with the requirements and limitations outlined in the Informed Consent Form (ICF) and this form.

Exclusion Criteria:

1. Active, known, or suspected autoimmune disease, or a history of an autoimmune disease, except for the following: vitiligo, alopecia areata, Graves's disease, psoriasis, or eczema that has not required systemic therapy within the last 2 years, hypothyroidism that is asymptomatic or requires only stable doses of hormone replacement therapy (due to autoimmune thyroiditis), type 1 diabetes that requires only stable doses of insulin replacement therapy, asthma that subsides completely in childhood and does not require intervention in adulthood, or diseases that do not recur in the absence of external triggers;
2. Prior treatment with immune checkpoint inhibitors, including, but not limited to, other anti-PD-1, anti-PD-L1 antibodies, CTLA-4 antibodies, or antibodies against immune co-stimulators (e.g., antibodies against ICOS, CD40, CD137, GITR, OX40 targets, etc.), or any other therapy targeting a tumor's immune mechanism of action;
3. Known hypersensitivity to any component and/or any excipient of the trial prescribed medication;
4. Immunosuppressive drugs or systemic corticosteroids for immunosuppression (\> mg/day of prednisone or other equivalent) within 2 weeks prior to trial dosing; topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids are permitted;
5. Received herbs with antitumor effects or drugs with immunomodulatory effects (e.g., thymidine, interferon, interleukin-2) within 2 weeks prior to the trial;
6. Active systemic infection requiring systemic treatment;
7. Serious infection within 4 weeks prior to the first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia;
8. Patients with untreated chronic hepatitis B, or HBV carriers with chronic hepatitis B virus (HBV) DNA greater than 1,000 IU/mL, or patients with active hepatitis C. Inactive HBsAg carriers, patients with hepatitis B who have received treatment and are in stable condition (HBV \< 1000 IU/mL), and patients with cured hepatitis C are eligible for enrollment. HCV antibody-positive subjects will be eligible for the study only if they have a negative HCV RNA test;
9. Known active tuberculosis (TB), patients with suspected active TB should undergo chest X-ray and sputum examination in conjunction with clinical signs and symptoms for exclusion;
10. Immunodeficiency or human immunodeficiency virus (HIV antibody positive);
11. Subjects with active inflammatory bowel disease or a history of such disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea). Subjects who are unable to swallow or who have malabsorption syndrome, uncontrolled nausea, vomiting, diarrhea, or other gastrointestinal disorders that severely interfere with drug intake and absorption;
12. Known interstitial lung disease that is symptomatic or may interfere with detection or treatment of immune-associated pneumonia;
13. Treatment with a live or attenuated vaccine administered within 4 weeks prior to the first trial dose, inactivated seasonal influenza virus vaccine is permitted;
14. Have received a prior allogeneic bone marrow transplant or solid organ transplant;
15. History of primary malignant tumor within the last 5 years;
16. Have undergone major surgery (e.g., open abdomen, open chest, organ resection, etc.) and severe trauma within 28 days prior to the first dose of the implantable infusion device is permitted;
17. With a history of gastrointestinal perforation, gastrointestinal fistula, or female genital fistula;
18. Uncontrolled other co-morbidities, symptoms, or medical history, including (i) persons with one of the following cardiovascular diseases or cardiovascular risk factors: myocardial infarction, unstable angina, pulmonary embolism, acute/continuous myocardial ischemia, cerebral vascular accident, transient ischemic attack, or other arterial or venous thrombosis, embolism, or cerebral ischemic event of clinical significance/requiring pharmacologic intervention; and persons who have had, within 6 months, a symptoms of congestive heart failure (New York Heart Association (NYHA) class III and above); (ii) clinically significant bleeding symptoms or a history of significant bleeding characteristics such as gastrointestinal bleeding, gastric ulcer bleeding, or vasculitis within 1 month prior to the first dose; (iii) clinically active hemoptysis, active diverticulitis, abdominal abscesses, and gastrointestinal obstruction; and (iv) uncontrolled pleural effusion, pericardial effusion, or ascites requiring Repeated drainage of ascites; ⑤ Abnormal liver or kidney development or history of surgery;
19. Pregnant or breastfeeding female patients; women of childbearing age who refuse to accept contraceptive measures during neoadjuvant immunotherapy;
20. Concurrent participation in other interventional clinical trials; participation in observational and non-interventional clinical trials is permitted;
21. Any condition that, in the judgment of the investigator, may result in risk in the receipt of the study drug or that would interfere with the evaluation of the safety of the study drug or the interpretation of the study results. Patients who, in the judgment of the Investigator, are unlikely to comply with the study steps, restrictions, and requirements are not permitted to participate in this study.

Where this trial is running

Hefei, Anhui and 11 other locations

• Anhui Provincial Cancer Hospital — Hefei, Anhui, China (Recruiting)
• Beiing Friendship Hospital, Capital Medical University — Beijing, Beijing Municipality, China (Recruiting)
• The First Affiliated Hospital (Southwest Hospital), Army Medical University (Third Military Medical University) — Chongqing, Chongqing Municipality, China (Recruiting)
• Gansu Provincial Maternity and Child-care Hospital — Lanzhou, Gansu, China (Recruiting)
• The Affiliated Tumor Hospital of Guangxi Medical University — Nanning, Guangxi, China (Recruiting)
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Xiangya Hospital, Central South University — Changsha, Hunan, China (Recruiting)
• Shengjing Hospital of China Medical University — Shenyang, Liaoning, China (Recruiting)
• Second People's Hospital of Sichuan (Sichuan Cancer Hospital) — Chengdu, Sichuan, China (Recruiting)
• Tianjin Medical University General Hospital — Tianjin, Tianjin Municipality, China (Recruiting)
• Women's Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)
• Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Kezhen Li

Conditions Cervical Cancer; Locally Advanced Cervical Cancer; PD-L1 Negative; Neoadjuvant Chemoimmunotherapy