A Randomized, Open-Label, Multicenter, Phase III Study to Evaluate MRG003 vs Cetuximab/Methotrexate as Second/Third Line of Treatment in Patient With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (RM-SCCHN)
The objective of this study is to compare the efficacy and safety of MRG003 versus cetuximab/methotrexate as second/third line of therapy in patients with RM-SCCHN who have previously failed PD-1 (L1) inhibitors and platinum-based therapy.
⁃ \- 1. Understands and provides written informed consent and willing to follow the requirements specified in protocol.
⁃ 2\. Age: ≥18 years and ≤75 years. 3. Life expectancy: ≥3 months. 4. Must have histologically or cytologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (including oral cavity, oropharynx, hypopharynx, larynx) who had previously failed PD-1 (L1) inhibitors and platinum-based therapy (in combination or sequential). Prior therapies should be no more than 2 lines.
⁃ Note: If disease progression occurred during neoadjuvant/adjuvant treatment or concurrent radiotherapy, or within 6 months after treatment discontinuation, the anti-tumor therapies (including platinum-based chemotherapy, anti-EGFR monoclonal antibody, PD-1 (L1) inhibitors, etc.) during neoadjuvant/adjuvant treatment or concurrent radiotherapy is counted as one line of prior treatment. Discontinuation or dose reduction of one drug, or change of platinum- or fluorouracil-based agents or PD-1 (L1) inhibitors without disease progression is considered as the same line of treatment.
⁃ 5\. Must have at least one measurable lesion per RECIST v1.1. Previously irradiated lesion cannot be considered as target unless there is documented progression three months after the last treatment of radiotherapy.
⁃ 6\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 1) with no deterioration within 2 weeks prior to enrollment.
⁃ 7\. Adequate bone marrow function, defined as meeting all of the following criteria and having no transfusion therapy within 3 weeks (21 days) or growth factors (G-CSF, EPO, etc.) support within 2 weeks (14 days) prior to dosing:
⁃ • Hemoglobin (Hb) ≥ 9.0 g/dL (90 g/L)
⁃ • Absolute neutrophil count (ANC) ≥ 1,500/mcL (1.5 × 109/L)
⁃ • Total platelet count (PLT) ≥ 100,000/mcL (100 × 109/L) 8. Adequate hepatic function, defined as all of the following:
⁃ • Total bilirubin (TBIL) ≤ 1.5×ULN;
⁃ • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN if no liver metastasis; ALT or AST ≤ 3.0×ULN in the presence of liver metastasis;
⁃ • Alkaline phosphatase (ALP) ≤ 1.5×ULN; ≤ 2×ULN in the presence of liver metastasis;
⁃ • Serum albumin ≥ 30 g/L 9. Coagulation: International Normalized Ratio (INR) or prothrombin time (PT), activated partial thromboplastin time (APTT) ≤ 1.5×ULN (unless patient is receiving anticoagulant therapy whose anticoagulant level should be within the therapeutic range). The laboratory parameters should be closely monitored by investigator if the patient is on anticoagulation therapy.
⁃ 10\. Adequate renal function, defined as Creatinine ≤ 1.5×ULN or creatinine clearance rate (Ccr) ≥ 50 mL/min if Creatinine \> 1.5×ULN (Creatinine clearance is calculated using the modified Cockcroft-Gault equation. Creatinine clearance can be calculated as Ccr = \[(140-age) × body weight (kg) × (0.85 for women only)\]/(72 × serum creatinine) if no local guidelines are available (without significant electrolyte imbalance that is not easily corrected).
⁃ 11\. Baseline Left Ventricular Ejection Fraction (LVEF) ≥ 50% measured by multiple-gated acquisition (MUGA) or echocardiogram (ECHO).
⁃ 12\. A negative serum or urine pregnancy test within 7 days prior to the first dose of study treatment (females of childbearing potential). If urine pregnancy test is positive or cannot be confirmed as negative, a confirmatory serum pregnancy test is required.
⁃ 13\. Patients, both females and males, of reproductive potential must agree to use adequate contraception during study treatment and for 180 days after the last treatment.
• Females of childbearing potential (who are not surgically sterile or postmenopausal for \< 1 year) who are willing to use adequate and reliable contraception such as avoidance of heterosexual activity, sterilization, oral contraceptives, injectable contraceptives, intrauterine devices, condoms, etc., during the study until 180 days after the last dose of study drug.
• Male patients who are willing to use latex condoms during any sexual contact with females of childbearing potential during treatment until 180 days after the last treatment, even if vasectomy has been successfully performed. Reservation of semen specimen prior to the first dose of study treatment is recommended for fertile males for potential future conception.