A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent Metastatic Nasopharyngeal Carcinoma

Inclusion Criteria:

• Willing to sign the ICF and follow the requirements specified in the protocol.
• Age: ≥18 years, ≤75 years
• Expected survival time>3 months.
• Patients with histologically confirmed unresectable, radiation-ineligible recurrentmetastatic nasopharyngeal carcinoma.
• Part A: Metastatic nasopharyngeal carcinoma that has failed or recurred or wasintolerant to at least 1 prior line platinum-based systemic chemotherapy andPD-1/PD-L1 inhibitors
• Part B: have documented failure of at least 2 prior lines of PD-1 (L1) andtherapysystemic chemotherapy, which include at least platinum-based regimen,gemcitabine, taxanes/capecitabine.
• Patients must have measurable lesions according to the Response Evaluation Criteria inSolid Tumors (RECIST v1.1).
• ECOG performance score 0 or 1.
• Organ functions and coagulation function must meet the basic requirements.
• No severe cardiac dysfunction with left ventricular ejection fraction (LVEF) ≥ 50%.
• Serum or urine pregnancy test negative within 72 hours before the first dose ofinvestigational drug.
• Patients with childbearing potential must use effective contraception during thetreatment and for 6 months after the last dose of treatment.

Exclusion Criteria:

• Grade ≥2 peripheral neuropathy per CTCAE v5.0.
• Is expected to require surgery or any other form of systemic or local anti-tumortherapy during the study.
• Received systemic chemotherapy, targeted therapy, biologics or immunotherapy, or majorsurgery (except for minor surgery within 2 weeks and fully recovered) within 3 weeksprior to the first dose of study treatment; received thoracic radiotherapy >30 Gywithin 6 months prior to the first dose of study treatment; received priorradiotherapy (except radiotherapy for CNS, wash-out period ≥ 28 days is required)within 14 days before the first dose of study treatment, received traditional Chinesemedicine with anti-tumor indications within the 2 weeks before the first dose of studytreatment.
• Known active central nervous system (CNS) metastases and/or meningeal metastases.Patients with brain metastases may participate provided they are treated and stable
• Residual toxicities due to prior anti-tumor therapy (including biologics, targetedtherapy, immunotherapy, chemotherapy or radiotherapy) or ≥ Grade 1 (CTCAE v5.0)clinically significant laboratory abnormality.
• History of severe cardiac dysfunction, stroke, or transient ischemic attack (TIA)within 6 months prior to enrollment. History of ventricular tachycardia or torsades depointes. Any clinically important abnormality in the rhythm, conduction, or morphologyof the resting ECG. Note: Patients with arrhythmia are eligible if they are receivingantiarrhythmic medication and the screening electrocardiogram (ECG) shows controllablerhythm and heart rate.
• Pulmonary embolism or deep venous thrombosis within 3 months prior to the first doseof study drug.
• Known history of malignancy (except for patients with cutaneous basal cell carcinoma,superficial bladder carcinoma, cutaneous squamous cell carcinoma, cervical carcinomain situ, or papillary thyroid carcinoma who have undergone successful curativetreatment) unless the patient has received potentially curative therapy and has nothad disease recurrence within 5 years starting from the treatment.
• Note: The 5-year recurrence-free time requirement does not apply to NPC for which thepatient is enrolled.
• Uncontrolled or poorly controlled hypertension (e.g., systolic blood pressure > 160mmHg or diastolic blood pressure > 100 mmHg) or diabetes mellitus (glycosylatedhemoglobin (HbA1c) > 8%).
• Patients with active bleeding, history of coagulopathy, or receiving coumarinanticoagulant therapy.
• History of ≥ Grade 3 immune-related AEs (irAEs), including skin toxicity, diarrhea,enteritis, fatigue, immune-related nephritis, immune-related hepatitis, and infusionreactions.
• Known allergic reactions to any component or excipients of MRG003 (citric acidmonohydrate, sodium citrate dihydrate, trehalose dihydrate, sodium chloride, andpolysorbate 80) or capecitabine/docetaxel, or known allergic reactions to otheranti-EGFR agents (including investigational drug) or to other monoclonal antibodies ≥Grade 3.
• Known active hepatitis B or C. Presence of other serious liver diseases, includingchronic autoimmune hepatic disorders, primary biliary cirrhosis or sclerosingcholangitis, alcoholic liver disease, or nonalcoholic steatohepatitis (NASH).
• Concurrent, serious, uncontrolled infection or known infection with humanimmunodeficiency virus (HIV) (HIV antibody positive), or diagnosis of acquiredimmunodeficiency syndrome (AIDS); or uncontrolled autoimmune disease; or previousallogeneic tissue/organ transplantation, stem cell or bone marrow transplantation, orprevious solid organ transplantation.
• Active bacterial, viral, fungal, rickettsial, or parasitic infection requiringsystemic anti-infection therapy (unless treated and resolved prior to studytreatment).
• Received live-virus vaccines within 30 days prior to the first dose of studytreatment. Seasonal influenza vaccines or approved COVID-19 vaccines that do notcontain live virus are permitted.
• History of moderate to severe dyspnea at rest or severe primary lung disease (currentneed for continuous oxygen therapy and oxygen saturation < 93% without oxygen therapy)due to advanced cancer or its complications, or history of any interstitial lungdisease (ILD) (including ILD that requires oral or intravenous corticosteroids) ornoninfectious pneumonitis
• Patients who are receiving an immunologically based treatment for any reason,including chronic use of systemic steroids equivalent to > 10 mg/day of prednisonewithin 7 days prior to the first dose of study treatment or at any time during thestudy. Note: Use of inhaled or topical steroids or systemic corticosteroids equivalentto ≤ 10 mg/day prednisone is permitted, as is short-term use of corticosteroids atdoses equivalent to > 10 mg/day prednisone (e.g., pre-medication prior to contrast).
• Chronic autoimmune or inflammatory disease requiring or receiving systemic therapywithin the last 2 years, including but not limited to inflammatory bowel disease,myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus,rheumatoid arthritis, Wegener's granulomatosis, Sjogren's syndrome, Guillain - Barre'ssyndrome, multiple sclerosis, vasculitis, or glomerulonephritis (exceptions: vitiligo,hypothyroidism on stable hormone replacement therapy, controlled asthma, type Idiabetes mellitus, Graves' disease, Hashimoto's disease, or with medical monitor'sapproval).
• Uncontrolled pleural, abdominal, pelvic effusion or pericardial effusion that requires ≥ 1 drainage per month.
• Patients who are using strong CYP3A4 inhibitors or inducers and for who stop the useis not recommended.
• Any patient with a positive pregnancy or is breast-feeding. Female and male patientswho are not expected to use adequate contraception during treatment and for 180 daysafter the last dose of treatment.
• Any other disease or clinically significant abnormality in laboratory parameters, orserious medical or psychiatric illnesses/conditions, substance abuse disorderincluding alcoholism, which in the judgment of the Investigator might compromise thesafety of the patient, integrity of the study, interfere with the patientparticipation in the study, or confound or compromise the study objectives and theirinterpretability.