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.

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

Squamous Cell Carcinoma of Head and Neck

Head and Neck Cancer

Cancer

Advanced Solid Malignancies

Advanced Solid Tumor

Advanced Solid Tumors

Solid Tumor, Adult

Neoplasms

Adenocarcinoma

Advanced Stage Solid Tumors

Amivantamab

Cisplatin

Carboplatin

Pembrolizumab

5-Flurouracil

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

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

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 .

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.

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.

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.

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.

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

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.

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.

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.

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.

Serum concentrations of amivantamab will be analyzed.

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

Participants will receive pembrolizumab, amivantamab and carboplatin.

Participants will receive pembrolizumab, 5-FU and carboplatin or cisplatin (platinum therapy).

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.

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

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 .

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.

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.

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.

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.

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

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.

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.

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.

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.

Participants will receive pembrolizumab, 5-FU and carboplatin or cisplatin (platinum
therapy).

Ironwood Cancer and Research Center

Providence St Jude Medical Center

Valkyrie Clinical Trials

Valkyrie Clinical Trials Murrieta

Stanford University Medical Center

Hartford Hospital

Yale Cancer Center

Florida Cancer Specialists South

Florida Cancer Specialists North Region

Florida Cancer Specialists East

University of Kentucky Medical Center

Karmanos Cancer Institute

Washington University School Of Medicine

NHO Revive Research Institute, LLC

Laura & Isaac Perlmutter Cancer Center at NYU Langone Hospital - Long Island

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health

Montefiore Medical Center

Bronx Veterans Affairs Medical Center

Carolina Cancer Research Center

Oregon Health And Science University

Tennessee Cancer Specialists

Texas Oncology - San Antonio

Texas Oncology-Central South

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

Trials at a glance

Trials at a glance

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

Outcome measures

Primary outcome measures

Secondary outcome measures