Cadonilimab (AK104) Plus Chemotherapy in Patients With Recurrent or Advanced Endometrial Cancer

NCT06066216 | Not Yet Recruiting Phase 2

• 1 other identifier: AK104-IIT-C-M-0032
• Study Type: interventional
• Target: 45
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, multi-center Phase II study of cadonilimab (AK104) combined with chemotherapy in patients with recurrent or advanced endometrial cancer. The primary objective is to evaluate objective response rate of cadonilimab plus chemotherapy.

Conditions

Endometrial Cancer; Endometrial Adenocarcinoma

Keywords

Endometrial Cancer; Immune Checkpoint Inhibitors (ICIs); Anti-PD-1/CTLA4 bi-specific antibody; Antiangiogenic agents; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Response Rate (ORR)

  ORR is the proportion of patients with best response of complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  from the first drug administration up to two years

Secondary Outcomes (5)

• Disease Control Rate (DCR)

  from the first drug administration up to two years

• Duration of response (DOR)

  from the first drug administration up to two years

• Progression-free Survival (PFS)

  from the first drug administration up to two years

• Overall survival (OS)

  from the first drug administration up to two years

• Adverse event (AE)

  From the subject signs the ICF to 90 days after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first

Other Outcomes (1)

• Biomarkers associated with the response to cadonilimab plus chemotherapy

  Samples taken prior to the first dose of drug to confirm the result of MSI-H/dMMR and PD-L1

Study Arms (1)

Cadonilimab+carboplatin/cisplatin+paclitaxel

EXPERIMENTAL

Cadonilimab (10 mg/kg, administered on the first day of each cycle, Q3W, until there is no clinical benefit)+ carboplatin(AUC=4-5, d1, Q3W, 6cycles) or cisplatin(75 mg/m2, d1, Q3W, 6cycles), +Paclitaxel(175 mg/m2, d1, Q3W, 6cycles), every 3 weeks (21 days) is a treatment cycle

Drug: Cadonilimab; Drug: Carboplatin; Drug: Cisplatin; Drug: Paclitaxel

Interventions

Cadonilimab DRUG

Injectable solution

Also known as: AK104

Cadonilimab+carboplatin/cisplatin+paclitaxel

Carboplatin DRUG

Injectable solution

Cadonilimab+carboplatin/cisplatin+paclitaxel

Cisplatin DRUG

Injectable solution

Cadonilimab+carboplatin/cisplatin+paclitaxel

Paclitaxel DRUG

Injectable solutionS

Cadonilimab+carboplatin/cisplatin+paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Patients must have had measurable stage III,IVA or recurrent endometrial cancer,and not suitable for curative radiotherapy or surgery.
• All patients were required to have histologic confirmation of the original primary tumor (submission of pathology report(s) is required). Patients with the following histologic types were eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, mucinous adenocarcinoma, dedifferentiated/undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, carcinosarcoma, etc.
• The subject has not received systematic chemotherapy in the advanced or recurrent disease, but is allowed to receive neoadjuvant therapy, adjuvant therapy (including chemotherapy, radiotherapy, or endocrine therapy) in the initial treatment stage, and the last adjuvant chemotherapy is required to be completed at least 6 months before enrollment. The final adjuvant radiotherapy, palliative radiotherapy (such as radiotherapy for bone metastases), and endocrine therapy should be completed at least 3 weeks before enrollment. For palliative radiotherapy of central nervous system (CNS) diseases, washout is allowed for one week.
• Recurrent endometrial cancer or advanced endometrial cancer that are not suitable for local treatment (including those with extensive abdominal and pelvic lesions, distant metastases, and those who cannot tolerate radiotherapy or surgery, if it is estimated that patients who may achieve surgery or radiotherapy after treatment are not suitable for enrollment).
• Prior antiangiogenic therapy is permitted.
• Signed Informed Consent Form (ICF).
• Provide tumor tissue samples fixed in formalin and embedded in paraffin for pathological examination
• In patients with measurable disease, lesions are defined and monitored by RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate organ function as defined by the following criteria:
• \) Blood routine examination standards to meet: (no blood transfusion within 14 days)：
• Hemoglobin of ≥90 g/L, white blood cell (WBC) ≥3×109/L, absolute neutrophil count (ANC) ≥1.5×109/L, platelets ≥100 ×109/L 2) Biochemical examination should meet the following criteria：
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN (however, patients with known liver metastasis who have AST or ALT level ≤ 5 × ULN may be enrolled)

You may not qualify if:

• Other malignant tumors in the past (within 5 years) or at the same time, excluding cured local tumors (such as basal cell skin cancer, squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ, etc.) and breast cancer and thyroid cancer that have no recurrence more than 3 years after the completion of radical surgery.
• Had received immunotherapy in the past, it includes immune checkpoint inhibitors (such as anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.) , immune checkpoint agonists (such as ICOS, CD40, CD137, GITR, OX40 antibody, etc.) , immune cell therapy, etc. Such subjects may be admitted with the consent of the sponsor.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Previous history of immunodeficiency; HIV antibody positive; Current long-term use of systemic corticosteroids or other immunosuppressants
• Subjects who are known to have active pulmonary tuberculosis (TB) and are suspected to have active TB need to undergo clinical examination to exclude them; Known active syphilis infection.
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
• Previous history of non-infectious pneumonia/interstitial lung disease requiring systemic glucocorticoid treatment or current presence of non-infectious pneumonia.
• Serious infections occur within 4 weeks before the first administration, including but not limited to comorbidities, sepsis, or severe pneumonia that require hospitalization; Active infections (excluding antiviral treatment for hepatitis B or C) that have received systemic anti-infective treatment within two weeks prior to the first administration.
• Untreated subjects with active hepatitis B (HBSAg positive and HBV-DNA above 1000 copies/ml (200 IU/ml) or above the lower limit of detection, whichever is higher), for subjects with Hepatitis B, anti-HBV therapy was required during study treatment; subjects with active hepatitis C (HCV antibody positive and HCV-RNA levels above the lower limit of detection) .
• Those who had a major surgical procedure or major trauma within 30 days before the first dose, or who had a major surgical plan within 30 days after the first dose (at the investigator's discretion); Minor local procedures (excluding central venous catheterization via peripheral venipuncture and implantable venous accessport) were performed within 3 days before the first dose.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
• There are currently uncontrolled comorbidities, including but not limited to symptomatic congestive heart failure (grade 2 and above according to the New York Heart Association functional classification), unstable angina, acute myocardial ischemia, poorly controlled arrhythmia, decompensated liver cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, Mental illness/social status that may limit subjects' compliance with research requirements or affect their ability to provide written informed consent.
• Previous history of myocarditis, cardiomyopathy, and malignant arrhythmia. Unstable angina, myocardial infarction, congestive heart failure, or vascular disease requiring hospitalization (such as aortic aneurysm at risk of rupture), or other cardiac impairment (such as poorly controlled arrhythmias, myocardial ischemia) that may affect study drug safety evaluation within 12 months prior to first administration of study drug; A history of esophageal Gastric varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, tumor-related gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding in the 6 months before the first dose; Any arterial thromboembolic event, NCI CTCAE version 5.0 Grade 3 or higher, venous thromboembolism, transient cerebral ischemia, cerebrovascular accident, Hypertensive crisis, or hypertensive encephalopathy, occurred within 6 months before the first dose; Acute exacerbation of chronic obstructive pulmonary disease within 1 month of first dose
• A history of incurable abdominal fistula or gastrointestinal perforation; During the screening period, imaging revealed obvious tumor invasion of the intestinal wall.
• During screening, imaging or clinical findings of gastrointestinal obstruction, including incomplete obstruction.

Sponsors & Collaborators

• Fujian Cancer Hospital: lead
• Fujian Provincial Hospital: collaborator
• The First Affiliated Hospital of Nanchang University: collaborator
• Zhangzhou Affiliated Hospital of Fujian Medical University: collaborator
• The First Affiliated Hospital of Bengbu Medical University: collaborator

Related Publications (1)

• Lin J, Liu T, Chen J, Lin Y, Chen X, Zhuo Y, Li Y, Jiang Y, Yang L, Tu C, Liu B, Zou J, Chen L, Sun Y. Efficacy and safety of cadonilimab combined with chemotherapy as the first-line treatment for primary advanced or recurrent endometrial cancer: a prospective single-arm open-label phase II clinical trial. BMJ Open. 2025 May 19;15(5):e094649. doi: 10.1136/bmjopen-2024-094649.

  PMID: 40389320 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Carboplatin; Cisplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Central Study Contacts

yang sun, doctor

CONTACT

+8615959028989; sunyang@fjzlhospital.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2023
• First Posted: October 4, 2023
• Study Start: February 1, 2024
• Primary Completion: October 31, 2025
• Study Completion (Estimated): October 31, 2026
• Last Updated: January 23, 2024

Record last verified: 2023-10