A Phase 3, Randomized, Open-Label, Multicenter Study of Amivantamab in Addition to Carboplatin and Pembrolizumab, Compared to Standard of Care Platinum and Pembrolizumab and 5-FU, in Participants with Treatment-Naïve Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

The primary objective of this study is to compare anti-tumor activity between amivantamab in combination with carboplatin and pembrolizumab versus standard of care platinum-based therapy with pembrolizumab and 5-fluorouracil in participants with treatment-naïve recurrent/metastatic head and neck squamous cell carcinoma. This comparison is clinically relevant for establishing the potential efficacy advantage of adding amivantamab, a bispecific antibody, to standard chemotherapy regimens in this patient population.

The secondary objectives include: assessment of additional measures of clinical benefit beyond the primary efficacy endpoint; evaluation of safety and tolerability profiles of the treatment regimens; assessment of disease symptoms, health-related quality of life (HRQoL), and treatment tolerability; and exploration of the relationship between pharmacokinetics or immunogenicity and selected endpoints in amivantamab-treated participants, including but not limited to efficacy and safety parameters.

This clinical trial enrolled a total of **308 participants** diagnosed with **treatment-naïve recurrent/metastatic head and neck squamous cell carcinoma**. The study population included both **male and female subjects** aged **18 years and older**. Participants were required to have **histologically or cytologically confirmed** disease considered incurable by local therapies and to be treatment-naïve for systemic therapy in the recurrent/metastatic setting. Eligible individuals demonstrated an **ECOG performance status** of 0-1, indicating good functional capacity. All participants were required to have **measurable disease** according to **RECIST v1.1** criteria at baseline. The trial population was selected based on these specific clinical characteristics to ensure a homogeneous cohort suitable for evaluating anti-tumor activity in this patient population.

This is a Phase 3, randomized, open-label, multicenter clinical trial evaluating the efficacy and safety of amivantamab administered in combination with carboplatin and pembrolizumab compared to standard of care treatment consisting of platinum-based therapy with pembrolizumab and fluorouracil in participants with treatment-naïve recurrent or metastatic head and neck squamous cell carcinoma. The investigational medicinal product amivantamab (JNJ-61186372) is administered as a solution for injection via subcutaneous use, while carboplatin, pembrolizumab, fluorouracil, and cisplatin are administered via intravenous use. The primary objective of this trial is to compare anti-tumor activity between the treatment arms. The primary endpoint is overall survival. Secondary endpoints include progression-free survival assessed according to RECIST version 1.1 criteria by blinded independent central review, objective response rate, duration of response, incidence and severity of treatment-emergent adverse events and laboratory abnormalities, changes in quality of life measures assessed by EORTC QLQ-HN43 and EORTC QLQ-C30 questionnaires, and pharmacokinetic parameters including serum amivantamab concentrations and anti-amivantamab antibodies.

Eligible participants must have histologically or cytologically confirmed recurrent or metastatic head and neck squamous cell carcinoma that is considered incurable by local therapies. Participants must be treatment-naïve for systemic therapy in the recurrent or metastatic setting. Additional inclusion criteria require participants to be 18 years of age or older with an ECOG performance status of 0 to 1 and measurable disease according to RECIST version 1.1 criteria. The trial is designed to enroll participants across multiple sites, with an estimated recruitment start date in January 2026 and an estimated study completion date in June 2029, resulting in an overall trial duration of approximately three and a half years.

Participant involvement in the study includes a screening visit to assess eligibility criteria and baseline characteristics. Following successful screening and enrollment, participants will be randomized to receive either the investigational treatment regimen or the standard of care comparator regimen. The study involves regular follow-up visits for disease assessment, safety monitoring, and collection of quality of life data. Disease assessments will be performed according to the protocol-specified schedule to evaluate tumor response using RECIST version 1.1 criteria. Safety assessments will be conducted throughout the treatment period to monitor for adverse events and laboratory abnormalities. Quality of life assessments will be performed at designated time points using validated questionnaires. An end-of-study visit will be conducted upon completion of the treatment phase or upon discontinuation from the study. The maximum treatment period for each medicinal product is specified as one cycle, with dosing schedules determined according to the protocol.

Participants may be withdrawn from the study under several conditions, including disease progression, unacceptable toxicity, participant request to discontinue, investigator decision based on clinical judgment, pregnancy, or loss to follow-up. Early termination may also occur if protocol-specified discontinuation criteria are met. All participants who discontinue study treatment will be followed for survival status and subsequent anticancer therapies as part of the long-term follow-up phase. The study design allows for comprehensive evaluation of both efficacy and safety outcomes while maintaining participant welfare throughout the duration of the trial.

The experimental medication amivantamab (JNJ-61186372) is administered as a solution for injection via subcutaneous route. The active substance is a protein-based therapeutic agent. The product will undergo repackaging and relabeling for use in this clinical trial. The maximum treatment period is designated as one year.

Carboplatin serves as an experimental medication in this study and is administered via intravenous use. The active substance is of chemical origin. The pharmaceutical form is provided in solution and will be repackaged and relabeled for trial purposes. The maximum treatment period is one year.

Pembrolizumab is utilized as an experimental medication in both treatment arms. The active substance is a protein-based therapeutic agent administered via intravenous use. The pharmaceutical form is a solution that will undergo repackaging and relabeling. The maximum treatment period is one year.

Fluorouracil (also known as 5-fluorouracil or 5-FU) functions as a comparator treatment in this study. The active substance is of chemical origin and is administered via intravenous use. The product will be repackaged and relabeled for use in the trial. The maximum treatment period is one year.

Cisplatin (also known as cis-diamminedichloroplatinum or CDDP) serves as a comparator treatment. The active substance is of chemical origin and is administered via intravenous use. The pharmaceutical form will be repackaged and relabeled for trial purposes. The maximum treatment period is one year.

The primary efficacy endpoint is Overall Survival (OS). Secondary efficacy endpoints include progression-free survival (PFS) assessed using RECIST v1.1 by blinded independent central review (BICR), objective response rate (ORR) as assessed by BICR, duration of response (DOR) as assessed by BICR, and ORR as assessed by the investigator. Additional secondary endpoints evaluate the proportion of participants with improved or stable symptoms relative to baseline, as measured by the EORTC QLQ-HN43 and symptom scales of the EORTC QLQ-C30. Change from baseline in functioning and overall health-related quality of life (HRQoL) will be assessed using functioning and global health scales of the EORTC QLQ-C30. Differences between treatment groups in the EORTC IL46 tolerability scale scores will also be evaluated.