A Study of MRG002 in the Treatment of HER2-positive Unresectable Locally Advanced or Metastatic Urothelium Cancer

Metastatic Urothelial Carcinoma Clinical Trial

Official title:

An Open-label, Single-arm, Multi-center, Phase II Clinical Study of MRG002 in the Treatment of Patients With HER2-positive Unresectable Locally Advanced or Metastatic Urothelium Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04839510
• Other study ID #: MRG002-006
• Status: Recruiting
• Phase: Phase 2
• Start date: April 20, 2021
• Est. completion date: September 2022

Study information

• Verified date: December 2021
• Source: Shanghai Miracogen Inc.
• Contact: Program Director
• Phone: 86-21-61637960
• Email: clinicaltrials[@]miracogen.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG002 as single agent in patients with HER2-positive unresectable locally advanced or metastatic urothelium cancer.

Description:

The study consists of two stages. In Phase IIa, approximately 25 subjects will be enrolled to evaluate the safety and preliminarily efficacy of MRG002. Based on the initial safety and efficacy data obtained from the Phase IIa, the study design of second stage Phase IIb single-arm study either will be continued or the trail will be terminated. If the Phase IIa data support the continuation of the study, in the second stage, approximately an additional 33 subjects will be enrolled to further evaluate the efficacy and safety of MRG002.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 58
• Est. completion date: September 2022
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Willing to sign the ICF and follow the requirements specified in the protocol.

2. Aged 18 to 75 (including 18 and 75), both genders.

3. Expected survival time = 12 weeks.

4. Patients with unresectable locally advanced or metastatic urothelium cancer confirmed by histopathology.

5. Failed in the prior one or more line of systemic chemotherapy.

6. HER2 positive (IHC 3 + or IHC 2 +) in the tumor specimens confirmed by central laboratory test.

7. Archival or biopsy tumor specimens should be provided (primary or metastatic).

8. Patients must have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

9. ECOG performance score 0 or 1.

10. Prior anti-tumor treatment-related AEs (NCI CTCAE v5.0 Criteria) have recovered to = Grade 1 (except alopecia, non-clinically significant or asymptomatic laboratory abnormalities).

11. No severe cardiac dysfunction with left ventricular ejection fraction (LVEF) = 50%.

12. Organ function must meet the basic requirements.

13. Coagulation function must meet the basic requirements.

14. Patients of childbearing potential must take effective contraceptive measures during the treatment and for 6 months after the last dose of treatment.

Exclusion Criteria:

1. History of hypersensitivity to any component of MRG002 or history of hypersensitivity of = Grade 3 to trastuzumab.

2. Received radiotherapy, chemotherapy, biotherapy, immunotherapy, or other anti-tumor drugs within 4 weeks prior to the first dose MRG002 treatment.

3. Patients with clinical symptoms such as pleural, abdominal or pericardial effusion requiring puncture drainage.

4. Patients with central nervous system (CNS) metastasis and/or neoplastic meningitis.

5. Any severe or uncontrolled systemic diseases.

6. Patients with poorly controlled heart diseases.

7. Evidence of active infections, including but not limited to Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) infection.

8. History of other primary malignancies.

9. History of interstitial pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc.

10. Peripheral neuropathy greater than Grade 1.

11. History of cirrhosis (decompensated cirrhosis Child-Pugh class B and C).

12. Patients with active autoimmune disease or a history of autoimmune disease, who are using immunosuppressive agents, or systemic hormone therapy and still receiving within 2 weeks prior to enrollment.

13. Received anti-tumor vaccine treatment 4 weeks prior to the first dose or planning to participate in anti-tumor vaccine trials.

14. Female patents with a positive serum pregnancy test or who are breast-feeding or who do not agree to take adequate contraceptive measures during the treatment and for 6 months after the last dose of study treatment.

15. Other conditions inappropriate for participation in this clinical trial, at the discretion of the investigator.

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• Locally Advanced Urothelial Cancer
• Metastatic Urothelial Carcinoma

Intervention

Drug:
• MRG002
Administrated intravenously

Locations

Country	Name	City	State
China	Beijing Chao-Yang Hospital,Capital Medical University	Beijing	Beijing
China	Beijing hospital	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing
China	The Fifth Medical Center of the PLA	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	The Affiliated Cancer Hospital of Xiangya School of Medicine(Hunan Cancer Hospital )	Changsha	Hunan
China	Xiangya hospital central south university	Changsha	Hunan
China	Sichuan provincial people's hospital	Chengdu	Sichuan
China	Army Medical Center of PLA	Chongqing	Chongqing
China	Chongqing University Cancer Hospital	Chongqing	Chongqing
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	SUN Yat-sen university Cancer center	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Haerbin medical university cancer hospital	Haerbin	Heilongjiang
China	Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)	Hangzhou	Zhejiang
China	The second Affiliated Hospital Zhejiang University School of Medical	Hangzhou	Zhejiang
China	Anhui provincial Cancer Hospital	Hefei	Anhui
China	The Second Hospital of Anhui Medical University	Hefei	Anhui
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Liuzhou People's Hospital	Liuzhou	Guangxi
China	Nantong Tumor Hospital	Nantong	Jiangsu
China	Changhai Hospital	Shanghai	Shanghai
China	Rui jin hospital	Shanghai	Shanghai
China	Zhongshan Hospital Affiliated to Fudan University	Shanghai	Shanghai
China	Liaoning Cancer hospital	Shenyang	Liaoning
China	ShenZhen Luohu People's Hospital	ShenZhen	Guangdong
China	JiLinGuoWen Hospital	Siping	Jilin
China	The Second Hospital of Tianjin Medical University	Tianjin	Tianjin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	The 1'Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Tongji Hospital	Wuhan	Hubei
China	Union hospital tongji medical college huazhong univerity ofscience and technology	Wuhan	Hubei
China	First Affiliated Hospital of Xi'an Jiaotong University	Xian	Shanxi
China	Qinghai University Affiliated Hospital	Xining	Qinghai
China	Henan Cancer Hospital	Zhengzhou	Henan
China	The Fifth Affiliated Hospital of Sun Yat-sen University	Zhuhai	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Miracogen Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) by Independent Review Committee (IRC)	ORR is defined as the percentage of patients with complete response (CR) and partial response (PR) as assessed by Independent Review Committee (IRC) according to RECIST v1.1.	Baseline to study completion, up to 12 months
Secondary	ORR by Investigator	ORR is defined as the percentage of patients with CR and PR as assessed by Investigator according to RECIST v1.1.	Baseline to study completion, up to 12 months
Secondary	Duration of Response (DoR)	DOR is defined as the time from first documented objective response to the first onset of tumor progression or death of any cause.	Baseline to study completion, up to 12 months
Secondary	Time to Response (TTR)	TTR is defined as the duration from the start of treatment to the first onset of CR or PR in tumor evaluation.	Baseline to study completion, up to 12 months
Secondary	Disease Control Rate (DCR)	DCR is defined as the percentage of patients who achieve CR, PR, and stable disease (SD) after treatment.	Baseline to study completion, up to 12 months
Secondary	Progression Free Survival (PFS)	PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause.	Baseline to study completion, up to 12 months
Secondary	Overall Survival (OS)	OS is defined as the duration from the start of treatment to death of any cause.	Baseline to study completion, up to 12 months
Secondary	Adverse Events (AEs)	Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug.	Baseline to 30 days after the last dose of study treatment
Secondary	Pharmacokinetics (PK) Parameter of MRG002: concentration-time curve	Concentration-time curve will be depicted based on pharmacokinetics concentration set (PKCS).	Baseline to 30 days after the last dose of study treatment
Secondary	Incidence of anti-drug antibody (ADA)	The incidence of ADA analysis will be summarized for all patients who received at least one cycle study treatment.	Baseline to 30 days after the last dose of study treatment