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

This study is a international, multicenter, open-label, randomized, parallel-group Phase III study

The study will include the following periods:

1. Screening Period 1

Includes Days -14 to -1 (prior to the first administration of the investigational product/comparator) 2. Main Period (Period 1)

The main study period includes Days 1-126

The Main Period begins with administration of cetuximab (RPH-002 or Erbitux®) and chemotherapy on Day 1 of Cycle 1. Chemotherapy continues for up to 6 cycles, each lasting 3 weeks (21 days). Chemotherapy agents are administered no earlier than 1 hour after completion of cetuximab infusion. Cetuximab is administered weekly for up to 18 doses

In Period 1, tumor response is assessed every 6 weeks 3. Screening Period 2

Includes Days -7 to 0 (prior to Visit 1 of the Maintenance Therapy Period)

During Screening Period 2, the patient's general condition and laboratory and instrumental test results are evaluated to determine eligibility for continuation of therapy in the Maintenance Therapy Period 4. Maintenance Therapy Period (Period 2)

Includes Days 127-386

In the Maintenance Therapy Period, patients with a tumor response or stable disease at Week 18 of Period 1 are included in the study. Tumor response is assessed according to RECIST 1.1 criteria: * Complete Response (CR) - disappearance of all target lesions, confirmed by CT scans for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be \<10 mm * Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions, maintained for at least 4 weeks compared with baseline (screening) measurements * Progressive Disease (PD) - at least a 20% increase in the sum of diameters of target lesions compared with the smallest sum recorded during the study (with an absolute increase of at least 5 mm), or the appearance of one or more new lesions * Stable Disease (SD) - neither sufficient shrinkage in the sum of diameters to qualify as partial response nor sufficient increase to qualify as progressive disease compared with the smallest sum recorded during the study