An Open-label, Single-arm, Multicenter, Phase II Clinical Study of Disitamab Vedotin Plus Cadonilimab as Therapy in Patients With HER2 Mutant Advanced or Metastatic Bile Duct Adenocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- Disitamab Vedotin Plus Cadonilimab
- Conditions
- Bile Duct Adenocarcinoma Non-Resectable
- Sponsor
- Zhejiang Cancer Hospital
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Objective response rate(ORR)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
It is a single arm, open-label, phase II cinical trial to evaluate the efficacy and safety of Disitamab Vedotin Plus Cadonilimab in second-line treatment of patients with Advanced or Metastatic Bile Duct Adenocarcinoma
Detailed Description
Biliary tract cancer is a group of highly heterogeneous and aggressive epithelial cancers, accounting for about 3% of all digestive system tumors. It is highly aggressive, and most of them are found in advanced stages, with extremely poor prognosis and a 5-year survival rate of less than 5%. The overexpression rate of HER2 in biliary tract tumors is about 26.5%, and the amplification rate is about 30.1%. In addition, HER2 mutations in biliary tract malignant tumors also include HER2 mutations. In addition, HER2 mutations in biliary malignant tumors also include HER2 mutations. Currently, anti-HER2 strategies have become a new hotspot for exploration in BTC. It is a single arm, open-label, phase II cinical trial conducted in China and plans to recruit 28 patients with HER2 Mutant Advanced or Metastatic Bile Duct Adenocarcinoma who have progressed through first-line treatment. The purpose of this study is to evaluate the efficacy and safety of second-line treatment with Disitamab Vedotin Plus Cadonilimab
Investigators
Ying Jieer
Chief physician
Zhejiang Cancer Hospital
Eligibility Criteria
Inclusion Criteria
- •Voluntarily agree to participate in the study and sign the informed consent;
- •Over 18 years old (including 18 years old), regardless of gender;
- •Expected survival ≥12 weeks;
- •the ECOG physical status score was 0 or 1;
- •For female subjects: they should be surgically sterilized, postmenopausal, or agree to use a medically approved method of contraception (e.g., IUD, birth control pills, or condoms) for the duration of the study treatment and for 6 months after the end of the study treatment period; they must have had a negative blood pregnancy test in the 7 days prior to study drug administration and must not be breastfeeding. For male subjects: should be surgically sterilized or agree to use a medically approved method of contraception during and for 6 months after the end of study treatment;
- •Able to understand the requirements of the trial. Willing and able to comply with the trial and follow-up procedures.
- •Adequate organ function
- •Bone Marrow Function: (no transfusion within 14 days prior to screening, no use of granulocyte colony stimulating factor \[G-CSF\], no use of drug correction) : i. Hemoglobin ≥90g/L; ii. Neutrophils ≥1.5×109/L; iii. Platelet ≥100×109/L;
- •Renal function: calculated creatinine clearance\* (CrCl) ≥ 60 mL/min, urine protein \< 2+ or 24-hour (h) urine protein quantification \< 1.0 g. The Cockcroft-Gault formula will be used to calculate CrCl;
- •\* The Cockcroft-Gault formula will be used to calculate CrCl CrCL (mL/min) = {(140 - age) × weight (kg) × F}/ (SCr(mg/dL) × 72) where F = 1 for males and F = 0.85 for females; SCr = serum creatinine
Exclusion Criteria
- •Patients who meet any of the following conditions will not be admitted to the study:
- •use of a clinical investigational drug within 4 weeks prior to the start of study treatment;
- •has received major surgical treatment (other than diagnostic) within 4 weeks prior to the start of study treatment and has not fully recovered or is expected to require major surgical treatment during the study;
- •treatment with a live attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of the need for such a vaccine during treatment or within 60 days of the last dose;
- •has had a serious arteriovenous thrombotic event, such as other than cerebrovascular (including transient ischemic attack), deep vein thrombosis, pulmonary embolism, or myocardial infarction, within 6 months prior to study drug administration
- •is suffering from an unstably controlled systemic disease, including diabetes mellitus, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, cirrhosis of the liver, angina pectoris, severe cardiac arrhythmia
- •is suffering from an active infection requiring systemic treatment;
- •a history of active tuberculosis;
- •a positive HIV test result;
- •active HBV or HCV infection; (Note: HBV DNA and/or HCV RNA testing is required for subjects who are HBsAg-positive and/or HCV antibody-positive during the screening period. Subjects who are negative for HBV DNA ≤500 IU/mL (or ≤2000 copies/mL) and/or HCV RNA are eligible for enrollment; HBsAg-positive subjects must be monitored for HBV DNA during the course of treatment).
Arms & Interventions
Experimental: Disitamab Vedotin Plus Cadonilimab
Disitamab Vedotin: 2.0mg/kg，ivgtt，D1, every 2 weeks for a treatment cycle. Cardonilimab: 6mg/kg，ivgtt，D1, every 2 weeks for a treatment cycle.
Intervention: Disitamab Vedotin Plus Cadonilimab
Outcomes
Primary Outcomes
Objective response rate(ORR)
Time Frame: 12 months
The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%)
Secondary Outcomes
- Progression-free survival (PFS)([Time Frame: up to 12 months])
- Disease control rate (DCR)([Time Frame: up to 12 months])
- Overall survival (OS)([Time Frame: up to 36 months])
- Incidence of Treatment-Emergent 3/4 Adverse Events([Time Frame: up to 12 months after enrollment or study close])