Disitamab Vedotin Plus Cadonilimab in Patients With HER2 Mutant Advanced or Metastatic Bile Duct Adenocarcinoma

NCT06383533 | Recruiting Phase 2

• 1 other identifier: IRB-2023-385
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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

Conditions

Bile Duct Adenocarcinoma Non-Resectable; HER2 Gene Mutation

Outcome Measures

Primary Outcomes (1)

• Objective response rate(ORR)

  The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%)

  12 months

Secondary Outcomes (4)

• Overall survival (OS)

  [Time Frame: up to 36 months]

• Progression-free survival (PFS)

  [Time Frame: up to 12 months]

• Disease control rate (DCR)

  [Time Frame: up to 12 months]

• Incidence of Treatment-Emergent 3/4 Adverse Events

  [Time Frame: up to 12 months after enrollment or study close]

Study Arms (1)

Experimental: Disitamab Vedotin Plus Cadonilimab

EXPERIMENTAL

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.

Drug: Disitamab Vedotin Plus Cadonilimab

Interventions

Disitamab Vedotin Plus Cadonilimab DRUG

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.

Experimental: Disitamab Vedotin Plus Cadonilimab

Eligibility Criteria

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

You may qualify if:

• 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
• liver function: (no albumin infusion within 14 days prior to screening): Serum total bilirubin ≤1.5×ULN (subjects with Gilbert syndrome allow total bilirubin ≤3×ULN) In subjects without liver metastasis, Aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP) ≤2.5×ULN; In subjects with liver metastasis, ALT and AST≤5×ULN, but without elevated bilirubin;
• Coagulation function: International Standardized Ratio (INR) and Activated partial thromboplastin time (APTT) ≤1.5 × ULN (unless the subject is receiving anticoagulant therapy and the INR and APTT are within the expected range for treatment with anticoagulants);
• Heart function: New York College of Cardiology (NYHA) rating \< 3; x. Left ventricular ejection fraction ≥50%;
• Nutritional status: (no albumin infusion within 14 days prior to screening): serum albumin ≥ 2.8 g/dL
• Histologically and/or cytologically confirmed non-treatable locally advanced or metastatic adenocarcinoma of the bile ducts, including intrahepatic or extrahepatic cholangiocarcinoma and gallbladder carcinoma

You may not qualify if:

• 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).
• Moderate or severe ascites with clinical symptoms that require therapeutic puncture and drainage (except for small amounts of ascites on imaging without clinical symptoms); uncontrolled or moderate or greater amounts of pleural effusion and pericardial effusion;
• Known history of severe allergy to any immunosuppressant, anti-HER2 drug;
• Presence of active autoimmune disease or history of autoimmune disease with potential for relapse (including, but not limited to, autoimmune hepatitis, interstitial pneumonitis, uveitis, enterocolitis, pituitary gland inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism \[enrollment is open to subjects who are manageable with hormone replacement therapy only\]); subjects with dermatological disorders that do not require systemic therapy such as vitiligo, psoriasis alopecia areata, controlled type I diabetes mellitus treated with insulin or asthma that has completely resolved in childhood and does not require any intervention in adulthood may be enrolled; asthmatics who require medical intervention with bronchodilators may not be enrolled;
• Patients who, in the judgment of the investigator, have other factors that may affect the results of the study or force the study to be terminated in midstream, such as alcoholism, drug abuse, other serious illnesses (including psychiatric illnesses) that require comorbid treatment, serious laboratory test abnormalities, accompanied by family or social factors, which would affect the safety of the patients;
• Pregnant or breastfeeding women or women/men who are planning to have children;

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

RECRUITING

MeSH Terms

Interventions

disitamab vedotin

Study Officials

• Jieer Ying

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jieer Ying, M.D.

CONTACT

13858195803; jieerying@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: April 22, 2024
• First Posted: April 25, 2024
• Study Start: May 1, 2023
• Primary Completion: May 1, 2025
• Study Completion: December 31, 2025
• Last Updated: April 26, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)