A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Head and Neck Cancer (OrigAMI-4)

A Phase 1b/2, Open-label Study of Amivantamab Monotherapy and Amivantamab in Addition to Other Therapeutic Agents in Participants With Head and Neck Squamous Cell Carcinoma

The purpose of this study is to determine safety and preliminary efficacy of amivantamab monotherapy, amivantamab in addition to pembrolizumab, amivantamab in addition to paclitaxel and amivantamab in addition to pembrolizumab and carboplatin in participants with recurrent/metastatic head and neck cancer. The study will also confirm the recommended Phase 2 combination dose (RP2CD) for amivantamab in addition to paclitaxel. The safety and preliminary efficacy of amivantamab in addition to pembrolizumab will also be determined in perioperative (before and after surgery) setting in participants with resectable locally advanced head and neck squamous cell carcinoma (HNSCC).

Study Overview

• Status: Recruiting
• Conditions: Squamous Cell Carcinoma of Head and Neck
• Intervention / Treatment: Biological: Amivantamab; Biological: Pembrolizumab; Drug: Paclitaxel; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Estimated): 287
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

Study Locations

• China
  • Beijing, China, 100142
    • Recruiting
    • Beijing Cancer Hospital of Peking University
  • Cheng Du Shi, China, 610041
    • Recruiting
    • West China School of Medicine/West China Hospital, Sichuan University
  • Linyi, China, 276002
    • Recruiting
    • Linyi Cancer Hospital
  • Shanghai, China, 200120
    • Recruiting
    • Shanghai East Hospital
  • Shanghai, China, 200032
    • Recruiting
    • Fudan Cancer Hospital
  • Wuhan, China, 430022
    • Recruiting
    • Union Hospital Tongji Medical College of Huazhong University of Science and Technology
• France
  • Avignon, France, 84918
    • Recruiting
    • Institut Sainte Catherine
  • Lille, France, 59000
    • Recruiting
    • Centre Oscar Lambret
  • Nantes, France, 44000
    • Recruiting
    • Chu Nantes
  • Paris, France, 75248
    • Recruiting
    • Institut Curie
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
• Germany
  • Essen, Germany, 45147
    • Recruiting
    • Universitaetsklinikum Essen
  • Leipzig, Germany, 04103
    • Completed
    • Universitaetsklinikum Leipzig
  • Stuttgart, Germany, 70174
    • Recruiting
    • Klinikum der Landeshauptstadt Stuttgart
• Japan
  • Nagoya, Japan, 464-8681
    • Recruiting
    • Aichi Cancer Center
  • Tokyo, Japan, 160-0023
    • Recruiting
    • Tokyo Medical University Hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Recruiting
    • University Malaya Medical Centre
  • Kuala Lumpur, Malaysia, 59100
    • Recruiting
    • Pantai Hospital Kuala Lumpur
• Poland
  • Gdansk, Poland, 80 214
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Gliwice, Poland, 44-102
    • Recruiting
    • Centrum Onkologii Instytut im M Sklodowskiej Curie Oddzial w Gliwicach
  • Warsaw, Poland, 02 781
    • Recruiting
    • Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
• South Korea
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Recruiting
    • Severance Hospital Yonsei University Health System
• Spain
  • Barcelona, Spain, 08908
    • Recruiting
    • Inst. Cat. Doncologia-H Duran I Reynals
  • Barcelona, Spain, 08035
    • Recruiting
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28034
    • Recruiting
    • Hosp. Univ. Ramon Y Cajal
  • Madrid, Spain, 28041
    • Recruiting
    • Hosp. Univ. 12 de Octubre
• Taiwan
  • Changhua, Taiwan, 500
    • Recruiting
    • Changhua Christian Hospital
  • Kaohsiung City, Taiwan, 833
    • Recruiting
    • Kaohsiung Chang Gung Memorial Hospital
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
  • Taipei, Taiwan, 112
    • Recruiting
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan, 33382
    • Recruiting
    • Linkou Chang Gung Memorial Hospital
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Recruiting
    • Addenbrooke's Hospital
  • Guildford, United Kingdom, GU2 7XX
    • Recruiting
    • The Royal Surrey County Hospital NHS Foundation Trust
  • London, United Kingdom, SW3 6JJ
    • Recruiting
    • Royal Marsden Hospital
  • London, United Kingdom, W1T 7HA
    • Recruiting
    • University College London Hospitals
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Imperial College London and Imperial College Healthcare NHS Trust
  • London, United Kingdom, SM2 5PT
    • Recruiting
    • Royal Marsden Hospital (Sutton)
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
• United States
  • California
    • La Jolla, California, United States, 92093
      • Completed
      • University of California at San Diego Moores Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Denver Anschultz Medical Campus
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago Medical Center (UCMC)
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Rogel Cancer Center
    • Detroit, Michigan, United States, 48201 2013
      • Recruiting
      • Karmanos Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina at Chapel Hill
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • University of Utah Huntsman Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Cohorts 1 to 5: Have histologically or cytologically confirmed recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) that is considered incurable by local therapies or for Cohort 6: have histologically or cytologically confirmed locally advanced (L/A) HNSCC that is considered curable by surgery Acceptable prior lines of therapy will be determined according to specific cohort 1, 2, 3A and 3B: (a) The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, or larynx; (b) Any known p16 status of tumor must be negative (Note: All participants with an oropharyngeal tumor must have results of p16 status, per local testing); (c) Participants must provide local testing results of programmed cell death ligand 1 (PD-L1) status, if available; Cohort 4: (d) Patients must have primary tumor location in oropharynx. Unknown primary tumors are not included (e) Primary tumor must be HPV-positive, confirmed by positive p16 test or high-risk human papillomavirus (HPV) in-situ hybridization (ISH) in tissue (current or archival) (f) Participants must provide local testing results of PD-L1 status, if available; Cohort 5 (g) The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, or larynx; (h) HPV status must be known (either positive or negative) for patients with primary tumor location in oropharynx with p16 test or high-risk HPV ISH in tissue; (i) Participants must provide local testing results of PD-L1 status; Cohort 6: (j) The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, or larynx; (k) Any known p16 status of tumor must be negative Note: All participants with an oropharyngeal tumor must have results of p16 status, per local testing Participants must provide local testing results of PD-L1 status (l) Participants must have Stage III or IVa disease (American Joint Committee on Cancer Staging Manual, 8th edition). Participants must have resectable disease
• Participants in Cohorts 1, 2, 3B, 4 and 5 must have measurable disease according to RECIST version 1.1. Participants in Cohort 3A and Cohort 6 must have evaluable disease (defined as having at least 1 non-target lesion according to RECIST version 1.1.
• Cohorts 1, 2, 3A, 3B, 4, and 5 only: Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less prior to the first dose of study treatment (except for alopecia or post-radiation skin changes [any grade], Grade less than or equal to [<=]2 peripheral neuropathy and Grade <=2 hypothyroidism stable on hormone replacement)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Participant must have adequate organ and bone marrow function as follows, without history of red blood cell transfusion, platelet transfusion, or use of granulocyte colony-stimulating factor within 7 days prior to the date of the laboratory test.

Participants should have: a) Hemoglobin >=9 grams per deciliter (g/dL); b) Neutrophils >=1.5 x 10^3/mcg; c) Platelets >=100 x 10^3/mcg

Exclusion Criteria:

• Uncontrolled illness including any medical history or current (non-infectious) interstitial lung disease (ILD)/ pneumonitis/ pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
• Participant with untreated brain metastases leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation
• Participant with a history of clinically significant cardiovascular disease
• Received prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives, whichever is longer, before the first administration of study treatment. The maximum required washout is 28 days
• Received radiotherapy for palliative purposes within 7 days of the first administration of study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Amivantamab Monotherapy (Dose Expansion); Participants will receive subcutaneous injection of amivantamab monotherapy 1600 milligrams (mg) (2240 mg, if body weight >=80 kilograms [kg]) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) once every week (q1w) for the remainder of Cycle 1 (Days 8 and 15), and every 3 weeks (q3w) from Cycle 2 onwards.	Biological: Amivantamab; Amivantamab will be administered subcutaneously.; Other Names: JNJ-61186372
Experimental: Cohort 3A (Dose Confirmation): Amivantamab + Paclitaxel; Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards, along with intravenous injection of paclitaxel 175 mg/m^2 q3w (on Day 1 of each 21-day cycle) in dose confirmation Cohort 3A. The recommended Phase 2 combination dose (RP2CD) of amivantamab will be determined in conjunction with study evaluation team (SET) in this dose confirmation Cohort 3A.	Biological: Amivantamab; Amivantamab will be administered subcutaneously.; Other Names: JNJ-61186372; Drug: Paclitaxel; Paclitaxel will be administered intravenously.; Other Names: TAXOL
Experimental: Cohort 3B (Dose Expansion): Amivantamab + Paclitaxel; Participants will receive subcutaneous injection of amivantamab at the determined RP2CD in addition to intravenous injection of paclitaxel 175 mg/m^2 q3w (on Day 1 of each 21-day cycle) as confirmed by SET in Cohort 3A.	Biological: Amivantamab; Amivantamab will be administered subcutaneously.; Other Names: JNJ-61186372; Drug: Paclitaxel; Paclitaxel will be administered intravenously.; Other Names: TAXOL
Experimental: Cohort 4: Amivantamab Monotherapy; Participants will receive subcutaneous injection of amivantamab monotherapy 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards.	Biological: Amivantamab; Amivantamab will be administered subcutaneously.; Other Names: JNJ-61186372
Experimental: Cohort 5: Pembrolizumab + Amivantamab + Carboplatin (Dose Expansion); Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards in addition to intravenous injection of pembrolizumab 200 mg on Day 1 of each cycle, and carboplatin (area under the concentration-time curve [AUC] 5 milligram per milliliter [mg/ml]*min) q3w on Day 1 of Cycles 1-6.	Biological: Amivantamab; Amivantamab will be administered subcutaneously.; Other Names: JNJ-61186372; Biological: Pembrolizumab; Pembrolizumab will be administered intravenously.; Other Names: KEYTRUDA; Drug: Carboplatin; Carboplatin will be administered intravenously.; Other Names: PARAPLATIN
Experimental: Cohort 2: Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in); Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards, along with intravenous (IV) injection of pembrolizumab 200 mg q3w (on Day 1 of each 21-day cycle).	Biological: Amivantamab; Amivantamab will be administered subcutaneously.; Other Names: JNJ-61186372; Biological: Pembrolizumab; Pembrolizumab will be administered intravenously.; Other Names: KEYTRUDA
Experimental: Cohort 6: Amivantamab + Pembrolizumab; Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight >=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight >=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2, along with intravenous injection of pembrolizumab 200 mg q3w (on Day 1 of each 21-day cycle) (Neoadjuvant Phase). In the adjuvant phase, pembrolizumab IV (200 mg) will be administered q3w from Adjuvant Cycle 1 Day 1 to Adjuvant Cycle 15 Day 1 and amivantamab SC 2,400 mg (3,360 mg for >80 kg) will be administered q3w from Adjuvant Cycle 4 Day 1 to Adjuvant Cycle 15 Day 1.	Biological: Amivantamab; Amivantamab will be administered subcutaneously.; Other Names: JNJ-61186372; Biological: Pembrolizumab; Pembrolizumab will be administered intravenously.; Other Names: KEYTRUDA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 3A: Number of Participants With Dose-limiting Toxicities (DLT)	Number of participants with DLTs will be reported. A DLT is defined as any of the following: treatment delay of greater than (>) 28 days due to unresolved toxicity, non-hematologic toxicity of Grade 3 or higher, hematologic toxicity of Grade 4 neutropenia persisting for >7 days or Grade 3 or higher thrombocytopenia with clinically significant bleeding or neutropenic fever of any grade, and liver enzyme elevation.	Up to 21 days
Cohort 3A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Severity	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment. Severity of TEAEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, and Grade 5= death related to adverse event.	2 years and 1 month
Cohorts 1, 2, 3B, 4 and 5: Objective Response Rate	ORR is defined as the proportion of participants who achieve either a partial response (PR) or complete response (CR), as defined by investigator assessment using Response Criteria in Solid Tumors (RECIST) version 1.1.	2 years and 2 months
Cohort 6: Major Pathologic Response (MPR)	The participants who achieve MPR at the time of surgery.	2 years and 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1 and 4: Maximum Observed Serum Concentration (Cmax) of Amivantamab	Cmax is defined as maximum observed serum concentration of amivantamab.	Predose up to 168 hours post dose on Day 1
Cohort 1 and 4: Time to Maximum Observed Serum Concentration (Tmax) of Amivantamab	Tmax is defined as time to maximum observed serum concentration of amivantamab.	Predose up to 168 hours post dose on Day 1
Cohort 1 and 4: Area Under the Serum Concentration Curve Verses Time Curve From Time t1 to t2 (AUC[t1-t2]) of Amivantamab	AUC(t1-t2) is defined as area under the serum concentration versus time curve from time t1 to time t2 of amivantamab.	Predose up to 168 hours post dose on Day 1
Cohort 1 and 4: Area Under the Curve From Time Zero to tau (AUC[0-tau]) of Amivantamab	AUC(0-tau) is defined as area under the curve from time 0 to tau hours of amivantamab.	Predose up to 168 hours post dose on Day 1
Cohort 1 and 4: Trough Serum Concentration (Ctrough) of Amivantamab	Ctrough is defined as the serum concentration of amivantamab.	Predose up to 168 hours post dose on Day 1
Cohort 1 and 4: Accumulation Ratio (R) of Amivantamab	Accumulation ratio (R) is calculated as area under the serum concentration-time curve from time zero to 168 hours (AUC[0-168]) value at Cycle 2 Day 1 dose divided by AUC(0-168) value after Cycle 1 Day 1 amivantamab dose.	Predose up to 168 hours post dose on Day 1
Cohorts 1, 2, 3B, 4 and 5: Duration of Response (DoR)	DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR.	2 years and 2 months
Cohorts 1, 2, 3B, 4 and 5: Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants achieving a confirmed complete or partial response, or durable stable disease (the second disease assessment) as defined by RECIST version 1.1.	2 years and 2 months
Cohorts 1, 2, 3B, 4 and 5: Progression-free Survival (PFS)	PFS is defined as the time from the first administration of study treatment until the date of objective disease progression or death, whichever comes first, based on investigator assessment using RECIST version 1.1.	2 years and 2 months
Cohorts 1, 2, 3B, 4, 5 and 6: Overall Survival (OS)	OS is defined as the time from the first administration of study treatment until the date of death due to any cause.	2 years and 2 months
Cohorts 1, 2, 3B, 4, 5 and 6: Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Severity	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment. Severity of TEAEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse events.	2 years and 1 month
Cohort 6: Event-Free Survival (EFS)	EFS is defined as the time from the first administration of study treatment until the date of radiographic disease progression, local or distant progression or recurrence as assessed with imaging or biopsy as indicated, or death due to any cause.	2 years and 2 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2024
• Primary Completion (Estimated): December 27, 2027
• Study Completion (Estimated): December 27, 2032

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 23, 2024
• First Posted (Actual): April 25, 2024

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Carboplatin; Paclitaxel; pembrolizumab; amivantamab
• Other Study ID Numbers: 61186372HNC2002 (Other Identifier: Janssen Research & Development, LLC); 2023-508418-40-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No