A Study of MRG003 in the Treatment of EGFR-positive Unresectable, Locally Advanced or Metastatic Biliary Tract Cancer

The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG003 as single agent in EGFR-positive unresectable locally advanced or metastatic biliary tract cancer patients who have progressed during or relapsed after at least one prior standard therapy.

The study consists of two stages. In Phase IIa, approximately 25 subjects will be enrolled to evaluate the safety and preliminarily efficacy of MRG003. Based on the 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 initial 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 MRG003.

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. EGFR positive 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 MRG003.
2. Received chemotherapy, radiotherapy, biologicals, immunotherapy, or other anti-tumor drugs within 4 weeks prior to the first dose.
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 the following ophthalmologic abnormalities：severe dry eye syndrome; keratoconjunctivitis sicca; severe exposure keratitis; any other condition that may increase the risk of corneal epithelial damage.
11. History of severe skin disease or chronic skin disease requiring oral or intravenous treatment.
12. History of interstitial pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc.
13. Peripheral neuropathy greater than Grade 1.
14. 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.
15. History of cirrhosis (decompensated cirrhosis Child-Pugh class B and C).
16. Received anti-tumor vaccine treatment 4 weeks prior to the first dose or planning to participate in anti-tumor vaccine trials.
17. 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.
18. Other conditions inappropriate for participation in this clinical trial, at the discretion of the investigator.