A Phase I Comparative Study of Pharmacokinetics, Safety, and Efficacy of RPH-002 and Erbitux® in Unresectable Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma

Inclusion Criteria:

Main Period (Period 1)

1. A voluntarily signed and dated Informed Consent form (ICF) of the patient
2. Histologically confirmed squamous cell carcinoma of the head and neck
3. Body mass index (BMI) between 18 and 30 kg/m\^2, inclusive
4. Documented unresectable locoregional recurrence or distant metastases, or progression after prior chemoradiotherapy or combination therapy completed \>3 months before screening, not amenable to local treatment (except cases with high risk of tumor lysis or bleeding), or newly diagnosed metastatic disease not previously treated with systemic therapy. Study treatment is first-line therapy
5. At least one measurable lesion per RECIST 1.1
6. Karnofsky performance status ≥70%
7. Screening laboratory values within the following limits (per local lab normal ranges):

   * Hemoglobin ≥90 g/L
   * Leukocytes ≥3.0 × 10\^9/L
   * Neutrophils ≥1.5 × 10\^9/L
   * Platelets ≥100 × 10\^9/L
   * Total bilirubin ≤2 × Upper Limit of Normal (ULN)
   * Aspartate aminotransferase (AST) ≤3 × ULN
   * Alanine aminotransferase (ALT) ≤3 × ULN
   * Estimated glomerular filtration rate (eGFR) ≥60 mL/min
8. Men and women of childbearing potential, and women within 2 years of menopause, must agree to use reliable contraception from informed consent through at least 6 months after study treatment; women of childbearing potential must have a negative urine pregnancy test. Women with no reproductive potential (≥2 years post-menopause or surgically sterile) are exempt
9. Ability and willingness to comply with study protocol and procedures for the planned duration of participation
10. Ability to undergo required pharmacokinetic sample collection, as judged by the investigator

Maintenance Therapy Period (Period 2)

1. Documented tumor response or disease stabilization per RECIST 1.1 by computed tomography (CT) or magnetic resonance imaging (MRI) at Week 18 of the Main Period
2. Ability and willingness to provide written informed consent for participation in Period 2
3. Karnofsky performance status ≥ 70%
4. Laboratory values within the following limits (per local lab normal ranges):

   * Hemoglobin ≥ 90 g/L
   * Leukocytes ≥ 3.0 × 10\^9/L
   * Neutrophils ≥ 1.5 × 10\^9/L
   * Platelets ≥ 100 × 10\^9/L
   * Total bilirubin ≤ 2 × ULN (upper limit of normal)
   * AST ≤ 3 × ULN
   * ALT ≤ 3 × ULN
   * eGFR ≥ 60 mL/min
5. Men and women of childbearing potential, and women within 2 years of menopause, must agree to use reliable contraception from informed consent through at least 6 months after study treatment; women of childbearing potential must have a negative urine pregnancy test. Women with no reproductive potential (≥2 years post-menopause or surgically sterile) are exempt

Exclusion Criteria:

Main Period (Period 1)

1. Prior therapy with cetuximab or other monoclonal antibody-based biologics
2. Chemotherapy, radiotherapy, or surgery for head and neck cancer within 3 months before screening
3. Any other surgery (except biopsy, implantable venous port placement, or urgent non-cancer surgery) within 3 months before screening
4. Nasopharyngeal carcinoma
5. Other malignancy within the past 5 years or prior/concurrent squamous cell carcinoma (except cured in situ ductal carcinoma, cervical carcinoma in situ, basal cell or squamous cell skin cancer)
6. Expected survival \< 3 months
7. Women who are pregnant or breastfeeding, or unwilling to use effective contraception during the study and for at least 6 months after
8. Significant cardiovascular disease per investigator, including uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥130 mmHg), coronary artery disease, myocardial infarction within 12 months, high-risk uncontrolled arrhythmias, or uncontrolled heart failure
9. Active infection requiring systemic antibiotic therapy
10. Ongoing systemic immunotherapy, hormone therapy, or other cancer treatments not specified in the protocol within 6 months prior to screening or during the study
11. Known or suspected brain metastases, including parenchymal, leptomeningeal, or dural involvement associated with symptoms
12. Positive screening for HBsAg, anti-HCV, anti-HIV1/2 antibodies, or syphilis within 3 months prior to screening
13. Conditions preventing compliance with the study protocol per investigator
14. Participation in another investigational drug study within 6 months prior to screening
15. Unstable medical conditions, including uncontrolled diabetes, psychiatric disorders, or uncontrolled seizures, that could interfere with protocol adherence
16. Known hypersensitivity to any component of study therapy or combination chemotherapy drugs
17. Excessive alcohol use (\>10 standard drinks/week) or history of alcoholism or substance abuse associated with symptoms. One standard drink = 250 mL beer, 125 mL wine, or 30 mL spirits

Maintenance Therapy Period (Period 2)

1. No documented tumor response or disease stabilization per RECIST 1.1 by CT or MRI at Week 18 of the Main Period
2. Women who are pregnant or breastfeeding, or unwilling to use effective contraception during the study and for at least 6 months after
3. Significant cardiovascular disease per investigator, including uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥130 mmHg), coronary artery disease, myocardial infarction within 12 months, high-risk uncontrolled arrhythmias, or uncontrolled heart failure
4. Active infection requiring systemic antibiotics
5. Ongoing systemic immunotherapy, hormone therapy, or other cancer treatments not specified in the protocol for Period 2
6. Known or suspected brain metastases, including parenchymal, leptomeningeal, or dural involvement associated with symptoms
7. Conditions preventing compliance with study procedures per investigator
8. Participation in another investigational drug study
9. Unstable medical conditions, including uncontrolled diabetes, psychiatric disorders, or uncontrolled seizures, that could interfere with protocol adherence
10. Excessive alcohol use (\>10 standard drinks/week) or history of alcoholism or substance abuse associated with symptoms. One standard drink = 250 mL beer, 125 mL wine, or 30 mL spirits