A Study of MRG003 in the Treatment of Patients With EGFR-positive Advanced or Metastatic Solid Tumors

This study consists of two parts: Phase I and Phase II. The objective of this study is to assess the safety and tolerability of MRG003 in combination with HX008 in patients with EGFR-positive advanced or metastatic solid tumors; and to explore the maximum tolerated dose (MTD) and to determine the recommended phase II dose (RP2D) of combination therapy; and to evaluate the preliminary efficacy, pharmacokinetics, and immunogenicity of combination therapy in the targeted study population.

Inclusion criteria

• Willing to sign the informed consent form and follow the requirements specified in the protocol.
• Aged 18 to 75 (including 18 and 75), both genders.
• BMI ≥17
• Life expectancy ≥ 12 weeks.
• Patients with EGFR-positive advanced or metastatic solid tumors, including non-small cell lung cancer (NSCLC), squamous cell carcinoma of head and neck (SCCHN), and nasopharyngeal carcinoma (NPC).
• EGFR-positive determined by immunohistochemistry (except NSCLC, SCCHN and NPC).
• Patients must have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
• The score of ECOG for performance status is 0 or 1.
• No severe cardiac dysfunction.
• Acceptable liver, renal, and hematologic function.
• Patients with childbearing potential must use effective contraception during the treatment and for 6 months after the last dose of treatment.

Exclusion criteria

• History of hypersensitivity to any component of the investigational product.
• Prior treatment with chemotherapy, biological therapy, immunotherapy, radiotherapy, investigational drugs, attenuated live vaccines, immunomodulators, CYP3A4 inhibitors/inducers, antibody-drug conjugates, Received major surgery without complete recovery, etc.
• Treatment with MMAE/MMAF ADC drugs
• Central nervous system metastasis.
• Toxic reaction or abnormal value of laboratory test caused by previous anti-tumor treatment ≥ 2 (CTCAE v5.0)
• Presence of peripheral neuropathy ≥ Grade 2.
• Liver function Child Pugh Grade B or Grade C。
• Pleural and peritoneal effusion or pericardial effusion with clinical symptoms requiring drainage.
• Poorly controlled systemic diseases (hypertension and hyperglycemia, etc.)
• Evidence of active infection of hepatitis B, hepatitis C or HIV.
• Patients with poorly controlled heart diseases
• History of ophthalmic abnormalities.
• History of severe skin disease requiring oral or intravenous therapy.
• History of interstitial pneumonia, radiation pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc.
• Active, known or suspected autoimmune disease or drug related immune disease or the disease history within the past 2 years.
• The patient is using immunosuppressant or systemic hormone therapy.
• Patients with any past arteriovenous bleeding within 3 months or current history of coagulation disorder.
• Any clinically significant VTE occurred within 6 months.
• Received allogeneic tissue/solid organ transplantation.
• Inoculate live vaccine within 30 days before the first dose.
• Patients 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 180 days after the last dose of study treatment.
• History of other primary malignant tumor diseases.
• Investigator considers which not suitable to participate in the clinical trial