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NCT Number: NCT07276399

A Study of Amivantamab in Addition to Standard of Care Agents (SOC) Compared With SOC Alone in Participants With Recurrent/Metastatic Head and Neck Cancer

The purpose of this study is to compare anti-tumor 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.

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Key information

Conditions

Squamous Cell Carcinoma of Head and Neck Carcinoma Carcinoma, Squamous Cell Head and Neck Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Monash Medical Centre, Clayton, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Be more than or equal to (>=) 18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater)
  • Have histologically or cytologically confirmed recurrent/metastatic (R/M) HNSCC that is considered incurable by local therapies: a. eligible primary tumor locations are the oral cavity, oropharynx, hypopharynx, or larynx; b. Must not have a primary tumor site of nasopharynx or primary tumor of unknown location; c. Must have documented local testing results per local regulations; d. Human papillomavirus (HPV) status must be known for participants with primary tumor location in oropharynx via p16 test, HPV DNA test, or high-risk HPV in situ hybridization (ISH). Any known p16, HPV DNA, or high-risk HPV ISH status of tumor must be negative
  • Be treatment-naive for systemic therapy in the R/M setting
  • Have an ECOG performance status of 0 or 1
  • Have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v).1.1

Exclusion criteria

  • Have an uncontrolled illness
  • Have untreated brain metastases or history of known presence of leptomeningeal disease
  • Have a history of clinically significant cardiovascular disease
  • Inadequate organ or bone marrow function
  • Known allergies, hypersensitivity, contraindications, or intolerance to excipients of: Amivantamab, Pembrolizumab, Carboplatin, Cisplatin, 5-FU and Hyaluronidase

Treatment and study plan

Amivantamab

Biological

Amivantamab will be administered.

Other names: JNJ-61186372, RYBREVANT

Pembrolizumab

Biological

Pembrolizumab will be administered.

carboplatin

Drug

Carboplatin will be administered.

5-flurouracil

Drug

5-Flurouracil will be administered for over 4-day infusion period.

Cisplatin

Drug

Cisplatin will be administered.

Primary outcomes

  1. Overall Survival (OS)

    Time frame: Up to approximately 3 years 7 months

    OS is defined as time from the date of randomization to the date of death due to any cause.

  2. Objective Response Rate (ORR) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)

    Time frame: Up to approximately 3 years 7 months

    ORR is defined as the percentage of randomized participants achieving a confirmed best overall response (BOR) of partial response (PR) or complete response (CR) by BICR using RECIST version 1.1 .

Secondary outcomes

  1. Progression-Free Survival (PFS) Using RECIST Version 1.1, as Assessed by BICR

    Time frame: Up to approximately 3 years 7 months

    PFS is defined as the time from randomization until the date of objective disease progression or death (due to any cause), whichever comes first, based on BICR assessment using RECIST v1.1, regardless of treatment discontinuation or start of subsequent anticancer therapy.

  2. Duration of Response (DOR) As Assessed by BICR

    Time frame: Up to approximately 3 years 7 months

    DOR as assessed by BICR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR as best response.

  3. ORR as Assessed by Investigator

    Time frame: Up to approximately 3 years 7 months

    ORR as assessed by the investigator is defined as the percentage of randomized participants achieving CR or PR, as defined by investigator assessment using RECIST v1.1 criteria.

  4. Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

    Time frame: Up to approximately 3 years 7 months

    TEAE is defined as any new or worsening adverse event (AE) occurring at or after the initial administration of study treatment through the day of last dose plus 30 days or prior to the start of subsequent anticancer therapy, whichever is earlier, or any follow-up AE with onset date and time beyond 30 days after the last dose of study treatment but prior to the start of subsequent therapy or any AE that is considered treatment-related regardless of the start date of the event.

  5. Number of Participants with Laboratory Abnormalities

    Time frame: Up to approximately 3 years 7 months

    Blood samples will be collected to determine the laboratory (serum chemistry and hematology) abnormalities.

  6. Percentage of Participants with Improved or Stable Symptoms Compared to Baseline as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module 43 (EORTC QLQ-HN43) Symptom Scale Score

    Time frame: Baseline, up to approximately 3 years 7 months

    EORTC QLQ-HN43, is a self-administered, 43-item questionnaire measuring the health-related quality of life (HRQoL) of participants with head and neck cancer. EORTC QLQ-HN43 includes 19 scales (anxiety, body image, coughing, dry mouth and sticky saliva, neurological problems, opening mouth, pain in the mouth, social contact, problems with senses, shoulder problems, skin problems, swelling in the neck, social eating, speech, swallowing, sexuality, problems with teeth, weight loss, and problems with wound healing). Responses to items are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much". Higher scores indicate worse health outcomes.

  7. Percentage of Participants with Improved or Stable Symptoms Compared to Baseline as Measured by EORTC QLQ-Core (C) 30 Symptom Scale Score

    Time frame: Baseline, up to approximately 3 years 7 months

    EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the HRQoL of participants with cancer. EORTC QLQ-C30 includes 3 symptom scales (fatigue, pain, and nausea and vomiting), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much". Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global health status, or more severe symptoms.

  8. Change from Baseline in Functioning HRQoL, as Measured by Functioning Scales of the EORTC QLQ-C30

    Time frame: Baseline, up to approximately 3 years 7 months

    EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the HRQoL of participants with cancer. EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), a global health status / quality of life scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much". Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global health status, or more severe symptoms.

  9. Change from Baseline in Overall HRQoL, as Measured by Global Health Scales of the EORTC QLQ-C30

    Time frame: Baseline, up to approximately 3 years 7 months

    EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the HRQoL of participants with cancer. EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), a global health status / quality of life scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much". Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global health status, or more severe symptoms.

  10. Differences Between Treatment Groups (Arms A and B) for EORTC Quality of Life (QLG) Item Library-46 (IL-46) Tolerability Scale Scores

    Time frame: Up to approximately 3 years 7 months

    EORTC IL46 is a single item used to measure the overall impact of treatment side effects. Responses are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." Higher score indicates more impact of treatment side-effects.

  11. Serum Concentration of Amivantamab

    Time frame: Up to approximately 3 years 7 months

    Serum concentrations of amivantamab will be analyzed.

  12. Number of Participants with Serum Anti-Amivantamab Antibodies

    Time frame: Up to approximately 3 years 7 months

    Participants who are positive to serum anti-amivantamab antibodies will be reported.

Study contacts

Contact information is provided by the study sponsor or research team.

Study Contact

CONTACT

[email protected]

844-434-4210

Sponsors and collaborators

Lead sponsor

Janssen Research & Development, LLC

Industry

Registry information

Official study title

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

Acronym: OrigAMI-5

Important dates

Study start
2025
Primary completion
2029
Study completion
2029
First posted
Dec 11, 2025
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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