An Open ,Single Arm, Prospective, Phase II Clinical Study on the First-line Treatment of Recurrent or Metastatic Muscle Invasive Bladder Cancer With Cadonilimab(AK104) Plus Nab-Paclitaxel

Tianjin Medical University Second Hospital1 site in 1 country20 target enrollmentOctober 10, 2022

ConditionsBladder Cancer

InterventionsCadonilimab

DrugsCadonilimab

Overview

Phase: Phase 2
Intervention: Cadonilimab
Conditions: Bladder Cancer
Sponsor: Tianjin Medical University Second Hospital
Enrollment: 20
Locations: 1
Primary Endpoint: Objective Response Rate(ORR)
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of Cadonilimab(AK104) combined with Nab -Paclitaxel as first line therapy for recurrent or metastatic muscle invasive bladder. Eligible participants will receive AK104 (up to 24 months) plus Nab-Paclitaxel (for 6 cycles) until radiologic disease progression, unacceptable toxicity, or withdrawal from the study, whichever occurred first. The primary endpoint is objective response rate.

Detailed Description

Cadonilimab(AK104) is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and CTLA-4, which has the potential to boost immune surveillance in tumors. The goal of this clinical phase II trial is to evaluate the efficacy and safety of AK104 combined with Nab-Paclitaxel as first line therapy for recurrent or metastatic muscle invasive bladder.

Registry

clinicaltrials.gov

Start Date

October 10, 2022

End Date

October 2025

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Tianjin Medical University Second Hospital

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Sign a written informed consent form before joining the group.
•Age\>18 years old.
•Patients with advanced metastatic bladder cancer confirmed histologically or pathologically.
•Have not received systemic treatment.
•Have measurable lesions (according to RECIST 1.1 standard, non lymph node lesions have a CT scan length of ≥ 10 mm, and lymph node lesions have a CT scan short diameter of ≥ 15 mm).
•ECOG PS score: 0-
•The expected survival period is greater than 12 weeks.
•The functions of important organs meet the following requirements (excluding the use of any blood components and cell growth factors within 14 days):
•(1) Blood routine: Neutrophils ≥ 1.5 × 10\^9/L;Platelet count ≥ 100 × 10\^9/L;Hemoglobin ≥ 90g/L.
•(2) Liver and kidney function:Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal value (ULN) or creatinine clearance rate ≥ 50 ml/min (Cockcroft Fault formula);Liver function: Aspartate aminotransferase (AST) ≤ 2.5 x ULN, alanine liver aminotransferase (ALT) ≤ 2.5 x ULN in subjects without liver metastasis; ALT and AST\<5 x ULN in liver metastasis subjects.;Total serum bilirubin (TBIL) ≤ 1.5 x ULN (excluding Gilbert syndrome where TBIL\<3.0 mg/dL);Urinary protein\<2+;If the urine protein is ≥ 2+, the 24-hour urine protein quantitative display must be ≤ 1g.

Exclusion Criteria

•The subject has previously or simultaneously suffered from other malignant tumors (excluding cured skin basal cell carcinoma and cervical carcinoma in situ).
•The subject is known to have previous allergies to macromolecular protein formulations or known to be allergic to the drug components used.
•The subject has any active autoimmune disease or a history of autoimmune disease (For example, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, decreased thyroid function, who have undergone thyroid surgery in the past cannot be included. subjects with vitiligo or complete remission of childhood asthma, who do not require any intervention in adulthood, can be included. subjects who require bronchodilators for medical intervention) Asthma cannot be included).
•The subject is currently using immunosuppressive agents or systemic or absorbable local hormone therapy to achieve immunosuppressive effects (dosage\>10mg/day of prednisone or other therapeutic hormones), and continues to use them within 2 weeks before enrollment.
•Ascites or pleural effusion with clinical symptoms require therapeutic puncture or drainage.
•Patients with clinically uncontrollable cardiac symptoms or diseases, such as: (1) NYHA grade 2 or above heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias that require treatment or intervention.
•The subject has an active infection or an unexplained fever\>38.5 degrees Celsius during the screening period or before the first administration (according to the researcher's judgment, the subject's fever caused by the tumor can be included in the group).
•Patients with past and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, and severe impairment of lung function with objective evidence.
•Subjects have congenital or acquired immune deficiency, such as HIV infected persons, or active hepatitis (transaminase does not meet the inclusion criteria, hepatitis B reference: HBV DNA ≥ 1000 IU/ml. hepatitis C reference: HCV RNA ≥ 1000 IU/ml). Chronic hepatitis B virus carriers with HBV DNA\<2000 IU/ml must receive antiviral treatment simultaneously during the trial period before they can be enrolled.
•Live vaccines may be administered less than 4 weeks before the study medication or during the study period.

Arms & Interventions

Cadonilimab (AK104) combined with Nab -Paclitaxel

Cadonilimab (10 mg/kg, administered on the first day of each cycle, Q3W, until there is no clinical benefit)+Nab-Paclitaxel(200 mg/m2, Q3W, 6cycles), every 3 weeks (21 days) is a treatment cycle

Intervention: Cadonilimab

Outcomes

Primary Outcomes

Objective Response Rate(ORR)

Time Frame: The last subject completes at least 24 weeks of follow-up (or disease progression)

The proportion of patients whose tumor volume is reduced to 30% and can be maintained for more than 4 weeks,Based on RECIST v1.1.

Secondary Outcomes

Overall Survival(OS)(24 months)
Progression-free Survival(PFS)(The last subject completes at least 24 weeks of follow-up (or disease progression))
Duration of Response(DOR)(The last subject completes at least 24 weeks of follow-up (or disease progression))
Adverse events(AEs）(24 months)