A Clinical Study of Disitamab Vedotin for Injection Combined With Penpulimab Injection in Neoadjuvant Therapy for Patients With HER2-expressing Cisplatin-intolerant cT2-T4aNxM0 Bladder Urothelial Carcinoma

NCT05488353 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: RC48-C039
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a one-arm exploratory clinical study of Disitamab Vedotin for Injection combined with Penpulimab Injection designed for cisplatin intolerant CT2-T4anxm0 bladder urothelial carcinoma patients.It will confirme the efficacy and safety of Disitamab Vedotin for Injection combined with Penpulimab Injection neoadjuvant treatment for cisplatin intolerant CT2-T4anxm0 bladder urothelial carcinoma patients. Finally, it will provide new evidence-based medical evidence for neoadjuvant therapy for such patients.

Conditions

Bladder Cancer

Keywords

HER2-expressing; Cisplatin-intolerant; Disitamab Vedotin for Injection; Penpulimab Injection

Outcome Measures

Primary Outcomes (1)

• pCR rate

  As assessed by the investigator,proportion of patients without residual tumor lesion among patients who underwent radical cystectomy after completion of clinical trial treatment.

  12 months

Secondary Outcomes (4)

• pathological downstaging rate

  12 months

• safety evaluation

  up to 3 years

• EFS EFS

  up to 3 years

• OS

  up to 3 years

Study Arms (1)

Single Arm

EXPERIMENTAL

Disitamab Vedotin for Injection, 2.0 mg/kg, given as an IV infusion on day 1, and Penpulimab Injection, 200 mg, on every 21 days On day 1 of the cycle, it is given as an intravenous infusion. Order of use: Disitamab Vedotin for Injection → Penpulimab Injection.

Drug: Disitamab Vedotin for Injection,Penpulimab Injection

Interventions

Disitamab Vedotin for Injection,Penpulimab Injection DRUG

After completion of all screening activities, patients confirmed to be eligible will enter the study and receive the following treatments. Neoadjuvant regimen (up to 4 cycles): Disitamab Vedotin for Injection, 2.0 mg/kg, given as an IV infusion on day 1, and Penpulimab Injection, 200 mg, on every 21 days On day 1 of the cycle, it is given as an intravenous infusion. Order of use: Disitamab Vedotin for Injection → Penpulimab Injection.

Single Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate in this trial, be able to sign a written informed consent form, and understand and agree to comply with the requirements of this study and the evaluation schedule.
• The age on the date of signing the informed consent form is 18 to 75 years old.
• If it is a patient with cT2-T4aNxM0 bladder urothelial carcinoma with histological diagnosis and imaging evaluation based on AJCC eighth edition bladder cancer TNM staging, if the investigator believes that there is residual disease after TURBT surgery; the histology is mixed type. Oncological patients require urothelial carcinoma predominance (at least 50%).
• Patients who are intolerant or not receiving cisplatin must be determined by the investigator. Patients who do not tolerate cisplatin chemotherapy must meet at least one of the following criteria:
• The performance status of ECOG is \>1;
• Creatinine clearance rate \< 60mL/min;
• Hearing loss ≥ grade 2 in the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5th edition;
• Peripheral neuropathy grade ≥ 2 in NCI-CTCAE 5th edition;
• Suffering from New York Heart Association grade 3 or higher heart failure.
• According to the assessment by the investigator, the need for radical cystectomy after neoadjuvant therapy, and the indications for radical cystectomy are met, and they are willing to undergo the surgery.
• HER2 testing at local laboratory using pre-treatment tumor specimens: HER2 expression confirmed after IHC results (defined as: IHC 1+ 2+ 3+).
• ECOG fitness status 0\~1.
• The patient's organ function is good, as measured by the following screening laboratory values ??(obtained ≤14 days prior to enrollment):
• a. Patients should not be on growth factor support ≤ 14 days prior to sample collection when screening for: i. Absolute neutrophil count ≥1.5×109/L; ii. Platelets≥100×109/L; iii. Hemoglobin≥90g/L; b. International normalized ratio or activated partial thromboplastin time ≤ 1.5 upper limit of normal (ULN); c. Serum total bilirubin≤1.5×ULN; d. AST, ALT and alkaline phosphatase≤2.5×ULN; e. The calculated creatinine clearance rate is greater than 30 mL/min;
• Non-conceptual or fertile women must be willing to use highly effective contraception during the study period and for ≥ 120 days after the last dose of Vidicitumumab or Piamprizumab (whichever occurs later), and Negative urine or serum pregnancy test results within ≤7 days prior to enrollment.

You may not qualify if:

• Previously received therapies targeting PD-1, PD-L1, PD-L2, CTLA4, Her2 or other antibodies or drugs that specifically target T cell co-stimulation or checkpoint channels.
• Received other approved systemic anticancer therapy or systemic immunomodulators (including but not limited to interferon, interleukin 2 and tumor necrosis factor) within 28 days before enrollment.
• Previously received radiotherapy for bladder cancer.
• Received drug treatment for tumors in the past, except for the following:
• For patients who have received systemic chemotherapy in the past, a treatment-free interval of at least 12 months from the last treatment to the start of neoadjuvant drug therapy;
• Local intravesical chemotherapy or immunotherapy ended at least 1 week before the initiation of study neoadjuvant drug therapy.
• Major surgery or major trauma within 28 days before enrollment (implantation of vascular access device and TURBT are not considered major surgery).
• Have been vaccinated with live vaccines within 28 days before enrollment (seasonal influenza vaccines are usually inactivated vaccines, so they are allowed to be used. Intranasal vaccines are live vaccines, so they are not allowed to be used).
• Received any Chinese herbal medicine or proprietary Chinese medicine for cancer control within 14 days before enrollment.
• Active autoimmune disease that requires systemic treatment, and the investigator evaluates that it has an impact on the study treatment.
• Long-term use of large amounts of hormones or other immunosuppressive agents is required, and the investigator evaluates that it has an impact on the study treatment.
• History of potassium, sodium, calcium abnormalities or hypoalbuminemia, interstitial lung disease, non-infectious pneumonia, or other uncontrolled systemic diseases, including diabetes, hypertension, cardiovascular disease, that the investigator believes may affect treatment (such as active heart disease within 6 months before enrollment, including: severe/unstable angina pectoris, myocardial infarction, symptomatic congestive heart failure and ventricular arrhythmia requiring drug treatment, etc.), etc.
• Untreated chronic hepatitis B subjects or hepatitis B virus (HBV) carriers with HBV DNA ≥ 500 IU/mL (2500 copies/mL) are not allowed to enter the study. Note: Inactive hepatitis B surface antigen carriers or patients with stable active HBV infection (HBV DNA \<500 IU/mL \[2500 copies/mL\]) after continuous antiviral therapy can be enrolled. HBV DNA testing is performed only in patients who are positive for antibodies to hepatitis B surface antigen.
• Patients with active hepatitis C are not eligible. Patients who tested negative for HCV antibodies during the screening period, or those who tested negative for HCV RNA after positive HCV antibody tests could be enrolled. Only patients who test positive for HCV antibodies require HCV RNA testing.
• A history of immunodeficiency (including positive human immunodeficiency virus HIV test, other acquired and congenital immunodeficiency diseases) or a history of allogeneic stem cell transplantation or organ transplantation.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead
• Third Affiliated Hospital, Sun Yat-Sen University: collaborator
• Nanfang Hospital, Southern Medical University: collaborator
• Southern Medical University, China: collaborator
• The Third Affiliated Hospital of Southern Medical University: collaborator

Related Publications (5)

• Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

  PMID: 15273542 BACKGROUND

• preliminary safety and efficacy results of RC48 combined with toripalimab in patients wit local advaned or metastatic Urothelial carcinoma(NCT04264936,RC48-C014)

  BACKGROUND

• An Open-label, Single-arm, Multicenter, Phase II Study of RC48 to Evaluate the Efficacy and Safety of Subjects With HER2 Overexpressing Locally Advanced or Metastatic Urothelial Cancer (NCT03809013,RC48-C009)

  BACKGROUND

• Sheng X, Yan X, Wang L, Shi Y, Yao X, Luo H, Shi B, Liu J, He Z, Yu G, Ying J, Han W, Hu C, Ling Y, Chi Z, Cui C, Si L, Fang J, Zhou A, Guo J. Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody-Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma. Clin Cancer Res. 2021 Jan 1;27(1):43-51. doi: 10.1158/1078-0432.CCR-20-2488. Epub 2020 Oct 27.

  PMID: 33109737 BACKGROUND

• Antitumor activity of neoadjuvant treatment with enfortumab vedotin monotherapy in patients with muscle invasive bladder cancer (MIBC) who are cisplatin-ineligible

  BACKGROUND

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

disitamab vedotin; Injections; penpulimab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Tianxin Lin

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tianxin Lin

CONTACT

86-20-34070379; sys_urology_gcp@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• 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: August 1, 2022
• First Posted: August 4, 2022
• Study Start: September 1, 2022
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: August 4, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share