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
2 other identifiers
interventional
287
11 countries
55
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2024
Longer than P75 for phase_1
55 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 22, 2024
CompletedFirst Submitted
Initial submission to the registry
April 23, 2024
CompletedFirst Posted
Study publicly available on registry
April 25, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 27, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 27, 2032
April 13, 2026
April 1, 2026
3.7 years
April 23, 2024
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
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 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
Cohort 6: Major Pathologic Response (MPR)
The participants who achieve MPR at the time of surgery.
2 years and 2 months
Secondary Outcomes (12)
Cohorts 1, 2, 3B, 4 and 5: Duration of Response (DoR)
2 years and 2 months
Cohorts 1, 2, 3B, 4 and 5: Clinical Benefit Rate (CBR)
2 years and 2 months
Cohorts 1, 2, 3B, 4 and 5: Progression-free Survival (PFS)
2 years and 2 months
Cohorts 1, 2, 3B, 4, 5 and 6: Overall Survival (OS)
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
2 years and 1 month
- +7 more secondary outcomes
Study Arms (7)
Cohort 1: Amivantamab Monotherapy (Dose Expansion)
EXPERIMENTALParticipants 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.
Cohort 2: Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in)
EXPERIMENTALParticipants 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).
Cohort 3A (Dose Confirmation): Amivantamab + Paclitaxel
EXPERIMENTALParticipants 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.
Cohort 3B (Dose Expansion): Amivantamab + Paclitaxel
EXPERIMENTALParticipants 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.
Cohort 4: Amivantamab Monotherapy
EXPERIMENTALParticipants 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.
Cohort 5: Pembrolizumab + Amivantamab + Carboplatin (Dose Expansion)
EXPERIMENTALParticipants 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.
Cohort 6: Amivantamab + Pembrolizumab
EXPERIMENTALParticipants 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.
Interventions
Amivantamab will be administered subcutaneously.
Pembrolizumab will be administered intravenously.
Paclitaxel will be administered intravenously.
Carboplatin will be administered intravenously.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (55)
University of California at San Diego Moores Cancer Center
La Jolla, California, 92093, United States
University of Colorado Denver Anschultz Medical Campus
Aurora, Colorado, 80045, United States
Yale Cancer Center
New Haven, Connecticut, 06520, United States
The University of Chicago Medical Center (UCMC)
Chicago, Illinois, 60637, United States
University of Maryland School of Medicine
Baltimore, Maryland, 21201, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201 2013, United States
Washington University School Of Medicine
St Louis, Missouri, 63110, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
University of Utah Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
University of Virginia
Charlottesville, Virginia, 22903, United States
Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
Beijing Cancer Hospital of Peking University
Beijing, 100142, China
West China School of Medicine/West China Hospital, Sichuan University
Cheng Du Shi, 610041, China
Linyi Cancer Hospital
Linyi, 276002, China
Fudan Cancer Hospital
Shanghai, 200032, China
Shanghai East Hospital
Shanghai, 200120, China
Union Hospital Tongji Medical College of Huazhong University of Science and Technology
Wuhan, 430022, China
Institut Sainte Catherine
Avignon, 84918, France
Centre Oscar Lambret
Lille, 59000, France
CHU Nantes
Nantes, 44000, France
Institut Curie
Paris, 75248, France
Gustave Roussy
Villejuif, 94805, France
Universitaetsklinikum Essen
Essen, 45147, Germany
Universitaetsklinikum Leipzig
Leipzig, 04103, Germany
Klinikum der Landeshauptstadt Stuttgart
Stuttgart, 70174, Germany
Aichi Cancer Center
Nagoya, 464-8681, Japan
Tokyo Medical University Hospital
Tokyo, 160-0023, Japan
Pantai Hospital Kuala Lumpur
Kuala Lumpur, 59100, Malaysia
University Malaya Medical Centre
Kuala Lumpur, 59100, Malaysia
Uniwersyteckie Centrum Kliniczne
Gdansk, 80 214, Poland
Centrum Onkologii Instytut im M Sklodowskiej Curie Oddzial w Gliwicach
Gliwice, 44-102, Poland
Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
Warsaw, 02 781, Poland
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Hosp Univ Vall D Hebron
Barcelona, 08035, Spain
Inst. Cat. Doncologia-H Duran I Reynals
Barcelona, 08908, Spain
Hosp. Univ. Ramon Y Cajal
Madrid, 28034, Spain
Hosp. Univ. 12 de Octubre
Madrid, 28041, Spain
Changhua Christian Hospital
Changhua, 500, Taiwan
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 833, Taiwan
National Taiwan University Hospital
Taipei, 100, Taiwan
Taipei Veterans General Hospital
Taipei, 112, Taiwan
Linkou Chang Gung Memorial Hospital
Taoyuan District, 33382, Taiwan
Addenbrooke's Hospital
Cambridge, CB2 0QQ, United Kingdom
The Royal Surrey County Hospital NHS Foundation Trust
Guildford, GU2 7XX, United Kingdom
Royal Marsden Hospital (Sutton)
London, SM2 5PT, United Kingdom
Royal Marsden Hospital
London, SW3 6JJ, United Kingdom
Imperial College London and Imperial College Healthcare NHS Trust
London, W12 0HS, United Kingdom
University College London Hospitals
London, W1T 7HA, United Kingdom
The Christie Nhs Foundation Trust
Manchester, M20 4BX, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 23, 2024
First Posted
April 25, 2024
Study Start
April 22, 2024
Primary Completion (Estimated)
December 27, 2027
Study Completion (Estimated)
December 27, 2032
Last Updated
April 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
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