A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck

Prior treatment

• Prior anti-tumor therapy with MMAE/MMAF ADCs
• Expected surgery or any other form of systemic or local anti-tumor therapy.
• History of systemic chemotherapy within 3 weeks before the first administration of the investigational drug, targeted small molecule therapy within 2 weeks or 5 half-life periods before the first administration (whichever is shorter), antitumor biological therapy or immunotherapy within 4 weeks before the first administration, or major surgery.
• History of pulmonary embolism or deep vein thrombosis within 3 months before the first administration of the investigational drug.
• Patients with a history of active bleeding, coagulopathy, or receiving coumarin anticoagulation therapy.
• Known allergic reaction to any ingredients or excipients of investigational drugs.
• Vaccination of live virus vaccine within 30 days before the first administration of the study drug. Inactivated seasonal influenza vaccine or approved COVID-19 vaccine is allowed.
• History of previous or concurrent interstitial pneumonia, radiation pneumonitis, severe chronic obstructive pulmonary disease, severe pulmonary dysfunction, symptomatic bronchospasm, etc.
• Patients receiving immunology-based treatment for any reason.
• Potent CYP3A4 inhibitors or inducers are in use and cannot be discontinued.

Other illness

• History of 4 or more systemic anti-tumor therapies for the recurrent or metastatic squamous cell carcinoma of head and neck.
• Uncontrolled or poorly controlled heart disease.
• Known history of malignancy.
• History of severe dermatosis.
• Uncontrolled or poorly controlled hypertension.
• Known active hepatitis B or C.
• Complicated with severe, uncontrolled infection or known human immunodeficiency virus (HIV) infection, or diagnosed as acquired immunodeficiency syndrome (AIDS); or uncontrolled autoimmune disease; or history of allogeneic tissue/organ transplantation, stem cell or bone marrow transplantation, or solid organ transplantation.
• Active bacterial, viral, fungal, rickettsia, or parasitic infections that require systemic anti-infective treatment.
• Other conditions that in the clinical judgement of the investigator make the patient not suitable for participation in this study.

Lab values

• Residual toxicity reactions caused by previous anti-tumor treatment or abnormal values of laboratory tests higher than grade 1 (CTCAE v5.0). Prior Grade 3 to 4 immune-related AE (irAE) or ≥Grade 2 heart-related irAE.

Other

• ≥Grade 2 peripheral neuropathy
• BMI≤17
• Known active CNS metastasis and/or cancerous meningitis.
• Uncontrolled pleural effusion, pericardial effusion or recurrent ascites.
• Women who are lactating or pregnant.

• Willing to sign the ICF and follow the requirements specified in the protocol.
• Expected survival time≥3 months.
• Patients with histologically confirmed unresectable recurrent or metastatic squamous cell carcinoma of head and neck.
• Failed prior platinum and/or anti-PD-1 treatment (Part A); failed or intolerant to at least one prior line of standard therapy (platinum-based regimen) (Part B)
• Patients must have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
• ECOG performance score 0 or 1.
• Organ functions and coagulation function must meet the basic requirements.
• Serum or urine pregnancy test negative within 7 days before the first dose of investigational drug.
• Patients with childbearing potential must use effective contraception during the treatment and for 6 months after the last dose of treatment.