A study of amivantamab in addition to standard of care agents compared with standard of care in participants with recurrent/metastatic head and neck cancer

INTERVENTION: The purpose of this study is to compare anti‐tumour activity of amivantamab in addition to pembrolizumab and carboplatin versus pembrolizumab, 5 fluorouracil (FU), and platinum therapy (carboplatin or cisplatin) in participants with refractory/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). HNSCC is a type of cancer that develops in the head and neck regions, including the outer tissue layer of the mouth and throat. This study will focus on participants with HNSCC who are treatment‐naive (have not received prior treatment) in the R/M setting. Study will be conducted in 3 periods: 1. Screening period (up to 28 days) 2. Treatment period (up to 24 months): Participants will be randomly (by chance) assigned to either of the 2 arms: ‐ Arm A: Pembrolizumab + Amivantamab + Carboplatin: • Dosage Level and Administration Routes: o Pembrolizumab IV 200 mg Q3W – Intravenous Infusion o Amivantamab SC 2400/3360 mg Q3W – Subcutaneous Injection o Carboplatin IV AUC 5 mg/mL•min Q3W – Intravenous Infusion • Amivantamab will be dosed weekly during Cycle 1 and Q3W starting on Cycle 2 Day 1. Pembrolizumab and carboplatin will be dosed Q3W starting from Cycle 1. The order of dosing combination agents will be: Pembrolizumab, Carboplatin, followed by amivantamab. ‐ Arm B: Pembrolizumab + 5‐Flurouracil (5‐FU) + Carboplatin or Cisplatin: • Dosage Level and Administration Routes: o Pembrolizumab IV 200 mg Q3W – Intravenous Infusion o 5‐FU IV 1000 mg/m2 per day for 4 days Q3W – Intravenous Infusion o Carboplatin IV AUC 5 mg/mL•min Q3W – Intravenous Infusion o Cisplatin 100 mg/m2 Q3W – Intravenous Infusion The sequence of drug administration will be: pembrolizumab, followed by carboplatin/cisplatin, then 5‐FU infusion. Pembrolizumab, carboplatin/cisplatin, and 5‐FU will be d CONDITION: Recurrent/metastatic head and neck squamous cell carcinoma ; Cancer PRIMARY OUTCOME: Overall survival (OS) and objective response rate (ORR; using RECIST v1.1) as assessed by Blinded Independent Central Review (BICR).; OS is defined as the time from the date of randomisation to the date of death due to any cause. ORR is defined as the proportion of randomised participants achieving a confirmed best overall response (BOR) or partial response (PR) or complete response (CR) by BICR using RECIST v1.1 criteria. SECONDARY OUTCOME: 1. Progression‐free survival is measured using RECIST v1.1 as assessed by blinded independent central review (BICR) at baseline and at scheduled tumour assessments throughout the study until disease progression or death ; 2. Duration of response is measured using RECIST v1.1 as assessed by BICR from the date of first documented response until disease progression or death ; 3. Objective response rate is measured using RECIST v1.1 as assessed by the investigator at baseline and at scheduled tumour assessments throughout the study ; 4. Incidence and severity of treatment‐emergent adverse events and laboratory abnormalities are measured using CTCAE v5.0 and standard laboratory tests at baseline and throughout the treatment and follow‐up periods ; 5. Proportion of participants with improved or stable symptoms relative to baseline is measured using the symptom scales of the EORTC QLQ‐HN43 and EORTC QLQ‐C30 at baseline and at scheduled PRO assessment timepoints during treatment and follow‐up ; 6. Change from baseline in functioning and overall health‐related quality of life is measured using the functioning and global health status scales of the EORTC QLQ‐C30 at baseline and at scheduled PRO assessment timepoints during treatment and follow‐up ; 7. Differences between treatment groups in tolerability are measured using the EORTC IL46 tolerability scale at scheduled PRO assessment timepoints during treatment ; 8. Serum amivantamab concentrations are measured using validated immunoassays at baseline, during treatment at predefined pharmacokinetic sampling timepoints, and at end of treatment ; 9. Serum anti‐amivantamab antibodies are measured using validated immunogenicity assays at baseline, during treatment at predefined sampling timepoints, and at end of treatment INCLUSION CRITERIA: 1. Be at least 18 years of age. 2. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 3. Have histologically or cytologically confirmed recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) that is considered incurable by local therapies and meets protocol specified criteria for location and testing. 4. Be treatment‐naïve for systemic therapy in the R/M setting, as per protool specified criteria. 5. Have measurable disease according to RECIST v1.1. If only one measurable lesion exists, it may be used for the screening biopsy as long as baseline tumour assessment scans are performed 7 or more days after the biopsyand if lesion remains acceptable as a target lesion after that time. Tumour lesions situated in a previously irradiated area are considered measurable if progression following radiation has been demonstrated in such lesions. 6. Consent to a screening biopsy or provide archival tissue sample per