Amivantamab in Recurrent/Metastatic Head and Neck Squamous Cell Cancer After Checkpoint Inhibitor and Chemotherapy: Pivotal Results From the Phase Ib/II OrigAMI-4 Study

B Barbara Burtness (Department of Internal Medicine and Yale Cancer Center, Yale School of Medicine, New Haven, CT) A Ari J. Rosenberg (Department of Medicine, Section of Hematology and Oncology and Comprehensive Cancer Center, University of Chicago, Chicago) P Paul L. Swiecicki J Jessica L. Geiger (Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH) M Marc Oliva (Institut Català d’Oncologia L’Hospitalet, Institut d’Investigació Biomèdica de Bellvitge, Barcelona) X Xuesong Lyu (Johnson & Johnson, Shanghai, China) J Joshua C. Curtin (Johnson & Johnson, Spring House, PA) K Kiichiro Toyoizumi (Johnson & Johnson, Tokyo, Japan) J John Xie (Johnson & Johnson, Raritan, NJ) M Mark Wade B Brooke Diorio (Johnson & Johnson, Titusville, NJ) A Aastha Kapoor (Johnson & Johnson, Spring House, PA) E Emrullah Yilmaz (Johnson & Johnson, Raritan, NJ) M Mahadi Baig (Johnson & Johnson, Raritan, NJ) P Priya Kim (Johnson & Johnson, Spring House, PA) R Remy B. Verheijen (Johnson & Johnson, Leiden, the Netherlands) S Sujay Shah (Johnson & Johnson, Spring House, PA) K Kevin J. Harrington (Institute of Cancer Research, Royal Marsden Hospital, London) C Cyril Abdeddaim D Douglas Adkins (Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Washington University School of Medicine, Alvin J. Siteman Cancer Center, and Barnes–Jewish Hospital, St. Louis) M Myung-Ju Ahn (Department of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea) A Aarti Bhatia I Irene Braña (Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Barcelona) B Benoit Calderon (Institut Sainte Catherine, Avignon, France) M Martin Forster J Jessica Geiger (1Cleveland Clinic, Cleveland, United States) Y Ye Guo D Dennis Hahn (Department of Hematology, Oncology, Stem-Cell Transplantation, and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany) M Missak Haigentz K Kevin Harrington L Lara Iglesias W William Ince (Addenbrooke's Hospital, Cambridge, United Kingdom) D Dongmei ji S Shigenori Kadowaki (Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan) A Andrzej Kawecki B Bhumsuk Keam (Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea) K Kathleen Kerrigan S Sung-Bae Kim (Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea) S Shau-Hsuan Li (Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan) S Sun Min Lim (Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea) J Jin-Ching Lin L Lei Liu J Jessica McDermott R Robert Metcalf (The Christie NHS Foundation Trust, Manchester, United Kingdom) E Ewa Pawlowska A Ari Rosenberg T Tomasz Rutkowski (Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland) M Malwinder Sandhu N Nisha Mohd Shariff S Siddharth Sheth (Division of Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC) A Alexander Spira (NEXT Oncology Virgina, Virgina Cancer Specialists Research Institute, Fairfax) A Ammar Sukari (Karmanos Cancer Institute, Detroit, MI) P Paul Loren Swiecicki H Hideki Tanaka (Institute for Aqua Regeneration (ARG), Shinshu University, 4−17−1 Wakasato, Nagano 380-8553, Japan) C Caroline Viala Z Zara Vidales H Hung-Ming Wang M Muh-Hwa Yang (Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan) K Kunyu Yang

Abstract

Single-agent paclitaxel or cetuximab after immune checkpoint inhibitor (ICI) and chemotherapy demonstrated objective response rates (ORRs) of 21%-24% in recurrent/metastatic (R/M) head/neck squamous cell cancer (HNSCC). Epidermal growth factor receptor (EGFR) and MET are overexpressed in R/M HNSCC. Amivantamab, an EGFR-MET bispecific antibody, may be a rational treatment. Cohort 1 of OrigAMI-4 (ClinicalTrials.gov identifier: NCT06385080 ) evaluated subcutaneous amivantamab administered every 3 weeks in participants with non-human papillomavirus R/M HNSCC after PD-(L)1 inhibitor and platinum-based chemotherapy. Prior anti-EGFR therapy and p16-positive oropharyngeal cancer were exclusionary. The primary end point was RECIST v1.1 ORR. Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. In 102 participants, blinded independent central review‑assessed ORR was 42% (95% CI, 32 to 52); the complete response rate was 15%. Median DoR was not reached (NR; 95% CI, 6.9 to NR); 56% of responses lasted ≥6 months. Investigator-assessed ORR was 47% (95% CI, 37 to 57). At a median follow-up of 11.8 months (range, 1.1-21.9), median PFS and OS were 6.8 months (95% CI, 5.2 to 8.3) and 12.5 months (95% CI, 10.2 to 16.8), respectively. Adverse events were consistent with previous experience with no new safety signals. Treatment-related discontinuations were low (8%). Amivantamab demonstrated greater antitumor activity in participants previously exposed to ICI and chemotherapy than has been reported for paclitaxel or cetuximab.

Article Details

Volume / Issue Vol. 44, Issue 24
Published August 20, 2026
Pages 2271-2277
ISSN 0732-183X
Publisher Lippincott Williams & Wilkins

Journal Info

Journal of Clinical Oncology

Lippincott Williams & Wilkins

ISSN: 0732-183X Health Sciences

Authors (59)

B

Barbara Burtness

Department of Internal Medicine and Yale Cancer Center, Yale School of Medicine, New Haven, CT

A

Ari J. Rosenberg

Department of Medicine, Section of Hematology and Oncology and Comprehensive Cancer Center, University of Chicago, Chicago

P

Paul L. Swiecicki

J

Jessica L. Geiger

Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH

M

Marc Oliva

Institut Català d’Oncologia L’Hospitalet, Institut d’Investigació Biomèdica de Bellvitge, Barcelona

X

Xuesong Lyu

Johnson & Johnson, Shanghai, China

J

Joshua C. Curtin

Johnson & Johnson, Spring House, PA

K

Kiichiro Toyoizumi

Johnson & Johnson, Tokyo, Japan

J

John Xie

Johnson & Johnson, Raritan, NJ

M

Mark Wade

B

Brooke Diorio

Johnson & Johnson, Titusville, NJ

A

Aastha Kapoor

Johnson & Johnson, Spring House, PA

E

Emrullah Yilmaz

Johnson & Johnson, Raritan, NJ

M

Mahadi Baig

Johnson & Johnson, Raritan, NJ

P

Priya Kim

Johnson & Johnson, Spring House, PA

R

Remy B. Verheijen

Johnson & Johnson, Leiden, the Netherlands

S

Sujay Shah

Johnson & Johnson, Spring House, PA

K

Kevin J. Harrington

Institute of Cancer Research, Royal Marsden Hospital, London

C

Cyril Abdeddaim

D

Douglas Adkins

Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Washington University School of Medicine, Alvin J. Siteman Cancer Center, and Barnes–Jewish Hospital, St. Louis

M

Myung-Ju Ahn

Department of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

A

Aarti Bhatia

I

Irene Braña

Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Barcelona

B

Benoit Calderon

Institut Sainte Catherine, Avignon, France

M

Martin Forster

J

Jessica Geiger

1Cleveland Clinic, Cleveland, United States

Y

Ye Guo

D

Dennis Hahn

Department of Hematology, Oncology, Stem-Cell Transplantation, and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany

M

Missak Haigentz

K

Kevin Harrington

L

Lara Iglesias

W

William Ince

Addenbrooke's Hospital, Cambridge, United Kingdom

D

Dongmei ji

S

Shigenori Kadowaki

Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan

A

Andrzej Kawecki

B

Bhumsuk Keam

Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea

K

Kathleen Kerrigan

S

Sung-Bae Kim

Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

S

Shau-Hsuan Li

Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

S

Sun Min Lim

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea

J

Jin-Ching Lin

L

Lei Liu

J

Jessica McDermott

R

Robert Metcalf

The Christie NHS Foundation Trust, Manchester, United Kingdom

E

Ewa Pawlowska

A

Ari Rosenberg

T

Tomasz Rutkowski

Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland

M

Malwinder Sandhu

N

Nisha Mohd Shariff

S

Siddharth Sheth

Division of Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC

A

Alexander Spira

NEXT Oncology Virgina, Virgina Cancer Specialists Research Institute, Fairfax

A

Ammar Sukari

Karmanos Cancer Institute, Detroit, MI

P

Paul Loren Swiecicki

H

Hideki Tanaka

Institute for Aqua Regeneration (ARG), Shinshu University, 4−17−1 Wakasato, Nagano 380-8553, Japan

C

Caroline Viala

Z

Zara Vidales

H

Hung-Ming Wang

M

Muh-Hwa Yang

Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan

K

Kunyu Yang