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

Sponsor

Fujian Cancer Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06066216

Collaborator

(none)

Enrollment

Arm

36.5

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Cancer Endometrial Adenocarcinoma	Drug: Cadonilimab Drug: Carboplatin Drug: Cisplatin Drug: Paclitaxel	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Cadonilimab (AK104) Plus Chemotherapy in the Treatment of Recurrent or Advanced Endometrial Cancer: a Multicenter, Prospective Phase II Trial

Anticipated Study Start Date :

Oct 15, 2023

Anticipated Primary Completion Date :

Oct 31, 2025

Anticipated Study Completion Date :

Oct 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cadonilimab+carboplatin/cisplatin+paclitaxel 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, 6-8cycles) or cisplatin(75 mg/m2, d1, Q3W, 6-8cycles), +Paclitaxel(175 mg/m2, d1, Q3W, 6-8cycles), every 3 weeks (21 days) is a treatment cycle	Drug: Cadonilimab Injectable solution Other Names: AK104 Drug: Carboplatin Injectable solution Drug: Cisplatin Injectable solution Drug: Paclitaxel Injectable solutionS

Arm

Intervention/Treatment

Experimental: Cadonilimab+carboplatin/cisplatin+paclitaxel

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, 6-8cycles) or cisplatin(75 mg/m2, d1, Q3W, 6-8cycles), +Paclitaxel(175 mg/m2, d1, Q3W, 6-8cycles), every 3 weeks (21 days) is a treatment cycle

Drug: Cadonilimab

Injectable solution

Other Names:

AK104

Drug: Carboplatin

Injectable solution

Drug: Cisplatin

Injectable solution

Drug: Paclitaxel

Injectable solutionS

Outcome Measures

Primary Outcome Measures

Response Rate (ORR) [from the first drug administration up to two years]
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

Secondary Outcome Measures

Disease Control Rate (DCR) [from the first drug administration up to two years]
Proportion of patients whose best overall response is either CR, PR, or SD
Duration of response (DOR) [from the first drug administration up to two years]
Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first
Progression-free Survival (PFS) [from the first drug administration up to two years]
Time from the date of first study treatment administration to the date of first documented tumor progression or death due to any cause, whichever occurs first
Overall survival (OS) [from the first drug administration up to two years]
Time from the date of first study treatment administration to the date of death due to any cause
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]
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), and clinically significant abnormal laboratory results

Other Outcome Measures

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]
Exploration of biomarkers that predict the efficacy of cadonilimab combined with chemotherapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years.
Patients must have had measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial cancer.
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, dedifferentiated/undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma.
The patient may have received: 1) no prior chemotherapy for treatment of endometrial cancer, or 2) prior adjuvant chemotherapy for treatment of endometrial cancer(e.g., paclitaxel/carboplatin alone or as a component of concurrent chemotherapy and radiation therapy [with or without cisplatin]), or 3) prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy, and/or palliative radiation therapy, or 4) prior hormonal therapy for treatment of endometrial cancer. These must be stopped at least three weeks before the first date of study treatment.
Recurrent or advanced endometrial cancer that is not suitable for local treatment, and advanced endometrial cancer that cannot tolerate radiotherapy.
Prior antiangiogenic therapy is permitted.
Recovering from the effects of recent radiation, surgery, or chemotherapy: if > 2 weeks before the study intervention, you may have previously received radiation with or without radiosensitizing chemotherapy. Participants had to recover from all radiation-related toxicity, no need to continue corticosteroid, and no radiation pneumonitis. For palliative radiotherapy for central nervous system (CNS) disease (≤2 weeks of radiotherapy) , washout was allowed for 1 week;
Signed Informed Consent Form (ICF).
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)
Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula)
TSH within normal limits. If TSH is not within normal range despite no symptoms of thyroid dysfunction, normal Free T3、Free T4 level are required.
Plasma cortisol≤ 1 × ULN 3) Urine protein ≤(+) , or 24-hour urine protein quantification less than 1 g; 4) International standard ratio (INR) and activated partial thromboplastin time ≤1.5 uln (unless anticoagulant therapy is used because of disease) ; 12. Adverse events from any previous treatment, except for symptomatic stable sensory neuropathy or alopecia ≤ CTCAE Grade 2, have returned to ≤ CTCAE grade 1 or baseline, except anemia; 13. Women of childbearing potential should have a negative serum or urine pregnancy test prior to receiving the first dose of study treatment; and should be willing to use one acceptable contraception (i.e., oral contraceptives, condoms, intrauterine devices [IUDs]) throughout the period of taking study treatment and for at least 3 months after the last dose of study drug(s).

Life expectancy exceeds 3 months.

Exclusion Criteria:

Known history of other malignancy (in the last 5 years) except localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder carcinoma, cervical carcinoma in situ, breast carcinoma in situ that has undergone curative therapy and breast carcinoma that has not recurred for > 3 years after 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

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.
Known presence of central nervous system metastases (stable state without surgery or radiation therapy), meningeal metastases, spinal cord metastases, or compression.
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
Previous history of abdominal fistula or gastrointestinal perforation associated with anti-VEGF therapy; the imaging results revealed the invasion of intestinal wall by neoplasm during screening.
During screening, imaging or clinical findings of gastrointestinal obstruction, including incomplete obstruction.
Previous history of severe bleeding or coagulation disorders; during screening, imaging showed that the neoplasm surrounded major blood vessels or had obvious necrosis and cavitation, and the investigators believed that participation in the study might increase risk of bleeding.
Toxicities from previous antitumour therapy did not resolve, defined as toxicities that did not return to grade 0 or 1 of NCI CTCAE version 5.0, or levels specified in the inclusion/exclusion criteria; Except for alopecia and sequelae of neurotoxicity related to previous platinum therapy. For subjects who develop irreversible toxicity and are not expected to worsen after administration of the study drug (EG, hearing loss), it may be included in the study after consultation with the medical examiner. Long-term radiation-induced toxicity in subjects who, in the judgment of the investigators, can not recover may be included in the study after consultation with the medical examiner.
Has received a live virus vaccine within 30 days prior to first administration of study drug or plan to be administered during the study period.
Known allergy to any component of any investigational drug, known history of severe hypersensitivity to other monoclonal antibody.
Known history of mental illness, substance abuse, alcohol, or drug abuse.
Is pregnant, breastfeeding women.
Any prior or current disease, treatment, or laboratory test abnormality that may confound the study endpoints, interfere with subjects' full participation in the study, or may not be in their best interest to participate in this study.
Local or systemic diseases caused by non-malignant tumors, or diseases or symptoms secondary to tumors, which can lead to higher medical risk and/or uncertainty in survival evaluation, such as tumor like leukemia reactions (white blood cell count>20 × 109/L), symptoms of cachexia (known to have lost more than 10% of body weight in the 3 months before screening), etc.