Upon entering the study, you will be randomly assigned to one of two treatment groups. This process is called randomization and determines which combination of medications you will receive.

One group will receive amivantamab combined with carboplatin and pembrolizumab.

The other group will receive the standard treatment consisting of a platinum-based medication with pembrolizumab and fluorouracil (also known as 5-FU).

If you are assigned to the first treatment group, you will receive amivantamab as an injection under the skin (subcutaneous injection), along with carboplatin and pembrolizumab, both given through a vein (intravenous infusion).

If you are assigned to the second treatment group, you will receive a platinum-based medication (either cisplatin or carboplatin) through a vein, combined with pembrolizumab and fluorouracil, also given through a vein.

The specific dosage, frequency, and duration of each medication will be determined by the study protocol and your medical condition.

Throughout the study, you will undergo regular medical examinations to monitor your health and the effects of the treatment.

These assessments will include measurements of your tumor size according to RECIST v1.1, which is a standardized method for evaluating how tumors respond to treatment.

Blood samples will be collected to measure medication levels in your system and to check for any laboratory abnormalities.

Your blood will also be tested for anti-amivantamab antibodies, which are substances your body might produce in response to the medication.

You will be asked to complete questionnaires at regular intervals to assess your symptoms and quality of life.

These questionnaires include the EORTC QLQ-HN43, which focuses on symptoms specific to head and neck cancer, and the EORTC QLQ-C30, which evaluates general cancer-related symptoms and functioning.

Another questionnaire called EORTC IL46 will assess treatment tolerability.

These evaluations help track changes in your symptoms and overall well-being during the study.

Your health will be closely monitored for any side effects or adverse events related to the study medications.

Any new symptoms, changes in your condition, or laboratory test abnormalities will be recorded and evaluated for their severity.

This ongoing safety monitoring continues throughout your participation in the study.

Imaging scans will be performed at specified intervals to evaluate how your tumor is responding to treatment.

These scans will be reviewed both by your study doctor and by an independent group of experts called BICR (Blinded Independent Central Review).

The evaluations will measure progression-free survival (the time during which your disease does not worsen), overall response rate (whether your tumor shrinks), and duration of response (how long any positive response lasts).

You will continue receiving the assigned treatment according to the study schedule until your disease progresses, you experience unacceptable side effects, or you decide to withdraw from the study.

The study protocol will specify the exact timing and frequency of medication administration, assessments, and follow-up visits.

After completing the treatment phase, you will continue to be followed for long-term outcomes.

The primary outcome being measured is overall survival, which refers to the length of time you remain alive after starting the study treatment.

This follow-up period is an essential part of the study and may continue for an extended period.