Clinical trial NCT04839510: A Study of MRG002 in the Treatment of HER2-positive Unresectable Locally Advanced or Metastatic Urothelium Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Locally Advanced Urothelial Cancer
Metastatic Urothelial Carcinoma
Keywords: MRG002
Antibody Drug Conjugate (ADC)
HER2
Urothelium Cancer
Lead sponsor: Shanghai Miracogen Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-09
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) by Independent Review Committee (IRC)
timeFrame: Baseline to study completion, up to 12 months
Secondary outcomes:
measure: ORR by Investigator
timeFrame: Baseline to study completion, up to 12 months
measure: Duration of Response (DoR)
timeFrame: Baseline to study completion, up to 12 months
measure: Time to Response (TTR)
timeFrame: Baseline to study completion, up to 12 months
measure: Disease Control Rate (DCR)
timeFrame: Baseline to study completion, up to 12 months
measure: Progression Free Survival (PFS)
timeFrame: Baseline to study completion, up to 12 months
measure: Overall Survival (OS)
timeFrame: Baseline to study completion, up to 12 months
measure: Adverse Events (AEs)
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: Pharmacokinetics (PK) Parameter of MRG002: concentration-time curve
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: Incidence of anti-drug antibody (ADA)
timeFrame: Baseline to 30 days after the last dose of study treatment
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui provincial Cancer Hospital
state: Anhui
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital，Capital Medical University
state: Beijing
city: Beijing
country: China
facility: The Fifth Medical Center of the PLA
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Chongqing
country: China
facility: Army Medical Center of PLA
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: SUN Yat-sen university Cancer center
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: ShenZhen
country: China
facility: ShenZhen Luohu People's Hospital
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou People's Hospital
state: Guangxi
city: Haerbin
country: China
facility: Haerbin medical university cancer hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union hospital tongji medical college huazhong univerity ofscience and technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya hospital central south university
state: Hunan
city: Changsha
country: China
facility: The Affiliated Cancer Hospital of Xiangya School of Medicine(Hunan Cancer Hospital )
state: Hunan
city: Nantong
country: China
facility: Nantong Tumor Hospital
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Siping
country: China
facility: JiLinGuoWen Hospital
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer hospital
state: Liaoning
city: Xining
country: China
facility: Qinghai University Affiliated Hospital
state: Qinghai
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Shanghai
country: China
facility: Rui jin hospital
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
city: Xian
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan provincial people's hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Tianjin
country: China
facility: The Second Hospital of Tianjin Medical University
state: Tianjin
city: Hangzhou
country: China
facility: The second Affiliated Hospital Zhejiang University School of Medical
state: Zhejiang
city: Hangzhou
country: China
facility: Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)
state: Zhejiang
city: Wenzhou
country: China
facility: The 1'Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Aiping Zhou, MD
role: PRINCIPAL_INVESTIGATOR
References: