Clinical trial NCT04837508: A Study of MRG002 in the Treatment of HER2-positive Unresectable, Locally Advanced or Metastatic Biliary Tract 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 Biliary Tract Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Advanced or Metastatic Biliary Tract Cancer
Keywords: MRG002
Antibody Drug Conjugate (ADC)
HER2
Biliary Tract Cancer
Lead sponsor: Shanghai Miracogen Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-08
Enrollment: 86
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 HER2-positive unresectable locally advanced or metastatic biliary tract cancer patients who have progressed during or relapsed after at least one prior stand therapy.

Detailed description: The study consists of two stages. In Phase IIa, 25-31 eligible subjects will be enrolled to evaluate the safety and preliminary efficacy of MRG002. Based on the initial safety and efficacy data obtained from the Phase IIa, the study design of the second stage Phase IIb single-arm study either will be adjusted or the trial will be stopped. If the Phase IIa data support the continuation of the study, in the second stage, approximately an additional 55 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 biliary tract cancer confirmed by histopathology.
5. Failed in the prior one or more standard therapies.
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 chemotherapy, radiotherapy, biologicals, immunotherapy, or other anti-tumor drugs within 4 weeks prior to the first MRG002 treatment.
3. Presence of clinical manifestation of biliary obstruction.
4. Patients with clinical symptoms such as pleural, abdominal or pericardial effusion requiring puncture drainage.
5. Presence of central nervous system (CNS) metastasis and/or neoplastic meningitis.
6. Any severe or uncontrolled systemic diseases.
7. Patients with poorly controlled heart diseases.
8. Evidence of active infections, including but not limited to Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) infection.
9. History of other primary malignancies.
10. History of interstitial pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc.
11. Peripheral neuropathy greater than Grade 1.
12. History of cirrhosis (decompensated cirrhosis Child-Pugh class B and C).
13. 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.
14. Received anti-tumor vaccine treatment 4 weeks prior to the first dose or planning to participate in anti-tumor vaccine trials.
15. 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.
16. 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: Bengbu
country: China
facility: The first affiliated hospital of bengbu medical college
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Guangzhou
country: China
facility: ZhuJiang Hospital of Southern Medical University
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Shenyang
country: China
facility: Liaoning Cancer Hospital&Institute
state: Liaoning
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Aiping Zhou, MD
role: PRINCIPAL_INVESTIGATOR
References: