Clinical trial NCT05687851: Study Of Cadonilimab Combined With Radiotherapy In The Treatment of Locally Advanced Cervical Cancer
Official title: A Single-arm, Multicenter, Phase II Study to Evaluate Cadonilimab（AK104） Combined With Radiotherapy For The Treatment of Locally Advanced Cervical Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Cervical Cancer
Keywords: Local advanced cervical cancer
Concurrent chemoradiotherapy
Lead sponsor: Chongqing University Cancer Hospital
Sponsor class: OTHER
Collaborators: name: Liaoning Cancer Hospital & Institute
name: Henan Cancer Hospital
name: Fujian Cancer Hospital
First posted: 2023-01-18
Enrollment: 33
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Cadonilimab（AK104）is a humanized IgG1 bispecific antibody that targets PD-1 and CTLA-4.

This is a single-arm, multicenter, open-label, phase II study, the purpose of this study is to evaluate the efficacy and safety of Cadonilimab plus radiotherapy in participants with locally advanced cervical cancer who do not tolerate chemotherapy.


Eligibility criteria: Inclusion Criteria:

1. Able to understand and voluntarily sign written informed consent.
2. Women aged ≥18 years at the time of study entry.
3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-2.
4. Life expectancy ≥12 weeks.
5. Intolerance to chemotherapy regimens.
6. Histologically confirmed cervical cancer.

   1. Histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix;
   2. Not receiving systemic anti-tumour therapy (including but not limited to radiotherapy, targeted therapy and immunotherapy, etc; concurrent chemotherapy is not included. Note: Removal or biopsy of pelvic lymph nodes or para-aortic lymph nodes for the purpose of clinical staging is allowed).
   3. Locally advanced cervical cancer（LACC）: The International Federation of Gynecology and Obstetrics (FIGO) 2018 Stage IB3/IIA2, IIB-IVA.
7. At least one measurable tumor lesion according to RECIST v1.1 criteria.
8. Available archived tumor tissue samples or recent biopsies.
9. Adequate organ function.
10. For fertile women with negative serum pregnancy and effective contraception within 7 days before administration (until 120 days after the last administration of the study drug and at least 180 days after radiotherapy)

Exclusion Criteria:

1. Other histological types of cervical cancer (eg, neuroendocrine carcinoma, small cell carcinoma, sarcoma, etc).
2. Evidence of distant metastases.
3. Have received total hysterectomy.
4. Subject with other active malignancies within 2 years prior enter the study.
5. Subject who cannot receive brachytherapy.
6. Active or prior documented autoimmune disease that may relapse.
7. History of interstitial lung disease or noninfectious pneumonitis.
8. Subject with the clinically significant cardio-cerebrovascular disease.
9. History of severe hypersensitivity reactions to other mAbs.
10. Prior allogeneic stem cell transplantation or organ transplantation.
11. Subjects who require systemic treatment with glucocorticoid (\>10 mg/day of prednisone or equivalent glucocorticoid) or other immunosuppressive agents within 14 days prior enter the study.
12. Receipt of live attenuated vaccines within 30 days prior to the first dose of the study drug.
13. Prior exposure to any experimental antitumor vaccines, or any agent targeting T-cell costimulation or immune checkpoint pathways (eg, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137 or anti-OX40 antibody, etc).
14. Any condition that, in the opinion of the Investigator, would interfere with the evaluation of the study drug or interpretation of subject safety or study results.

Primary outcomes:
measure: ORR assessed by Investigator
timeFrame: Up to 2 years
Secondary outcomes:
measure: DCR
timeFrame: Up to 2 years
measure: PFS
timeFrame: Up to approximately 30 months
measure: OS
timeFrame: Up to approximately 40 months
measure: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score and Physical Function Score.
timeFrame: Baseline and up to approximately 40 months
measure: Number of participants with adverse events (AEs)
timeFrame: Up to approximately 40 months
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Chongqing university Cancer Hospital
state: CHN
Study officials:
affiliation: Chongqing University Cancer Hospital
name: Qi Zhou, MD
role: PRINCIPAL_INVESTIGATOR
References: