A Study of RC48-ADC Combined With Cadonilimab（AK104）in the Treatment of HER2-expression Locally Advanced or Metastatic Urothelial Carcinoma

An Open-label, Single-arm, Multi-center, Phase II Study to Evaluate the Efficacy and Safety of RC48-ADC Combined With AK104 in HER2-expression Locally Advanced or Metastatic Urothelial Carcinoma

This study will evaluate the efficacy and safety of RC48-ADC combined with AK104 in HER2-expression locally advanced or metastatic urothelial carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Drug: RC48-ADC; Drug: AK104

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wang Xin Doctor; Phone Number: +86(010)87787170; Email: WXCAMS@126.com

Study Locations

• China
  • Beijing
    • 北京, Beijing, China, 100000
      • Recruiting
      • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
      • Principal Investigator: Nianzeng Xing
      • Contact: Xin Wang; Phone Number: 010-87787170; Email: WXCAMS@126.com
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • Recruiting
      • Shanxi Province Cancer Hospital
      • Principal Investigator: Nianzeng Xing
      • Contact: Xin Wang; Email: WXCAMS@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntary agreement to provide written informed consent.
• Male or female, Age ≥ 18 years.
• Predicted survival ≥ 6 month.
• Histologically and/or cytologically confirmed locally advanced or metastatic urothelial carcinoma (including urothelial carcinoma originating in the renal pelvis, ureter, bladder, or urethra).
• Pior not received systemic therapy, and can not tolerant cisplatin or refuse chemotherapy.
• HER2 expressing (i.e. IHC 1+ 2+ or 3+) as confirmed by the local lab.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Have at least one evaluable lesion (RECIST 1.1 criteria)
• Adequate organ function, evidenced by the following laboratory results within 7 days prior to the study treatment.
• Male and female participants are eligible to participate if they agree to the contraception use as per study protocol.
• Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

• Has received other antitumor therapy before planned start of trial treatment.
• Previously received allogeneic stem cell or parenchymal organ transplantation;
• Previously or currently suffering from congenital or acquired immunodeficiency diseases;
• known or suspected to have a history of allergies to similar drugs such as RC48-ADC and anti-PD-1, or has a history of hypersensitivity to chimeric or humanized antibodies or fusion proteins, or is allergic to excipients of the study drug.
• Diagnosed with HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive, or HIVAb positive.
• Has received a live virus vaccine within 4 weeks of planned start of trial treatment.
• NYHA Class III or IV heart failure.
• Suffering from active infection requiring systemic treatment.
• Uncontrolled hypertension, diabetes, Interstitial lung Disease, or COPD;
• Required systemic treatment with glucocorticoid (>10 mg/day of prednisone or equivalent glucocorticoid) or other immunosuppressive agents within 14 days prior to enter the trial.
• History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Pregnancy or lactation.
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RC48-ADC plus cadonilimab（AK104）	Drug: RC48-ADC; RC48-ADC （2.0 mg/kg，intravenous (IV) infusion，Q2W）, combined with cadonilimab（AK104）; Drug: AK104; AK104（6.0 mg/kg，intravenous (IV) infusion，Q2W）combined with RC48-ADC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR assessed by Investigator	The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR per RECIST v1.1.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DCR	The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.	Up to 2 years
PFS	Progression-free survival is defined as the time from the start of treatment until the first documentation of disease progression or death due to any cause, whichever occurs first.	Up to approximately 30 months
OS	OS is the time from randomization to death due to any cause safety	Up to approximately 40 months

Collaborators and Investigators

• Sponsor: Shanxi Province Cancer Hospital
• Collaborators: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: December 12, 2023
• First Submitted That Met QC Criteria: December 12, 2023
• First Posted (Actual): December 21, 2023

Study Record Updates

• Last Update Posted (Actual): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell
• Other Study ID Numbers: AK104-RC48 UC 01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No