Squamous Cell Carcinoma of Head and NeckPhase 1/2OrigAMI-4NCT06385080
A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Head and Neck Cancer
A Phase 1/2 study testing Amivantamab, Pembrolizumab and Paclitaxel in people with Squamous Cell Carcinoma of Head and Neck, run by Janssen Research & Development, LLC at 56 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma of Head and Neck
- What is being tested?
- Amivantamab, Pembrolizumab and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 287 participants
- Where
- 56 sitesin 11 countries
- Study dates
- 22 Apr 2024to 28 Jul 2033
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
56 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
56 sites in 11 countries
United States15 sites, 14 recruiting
- Recruiting
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
- Recruiting
University of Colorado Denver Anschultz Medical Campus
Aurora, Colorado, 80045
- Recruiting
University of Maryland School of Medicine
Baltimore, Maryland, 21201
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
- Recruiting
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
- Recruiting
University of Virginia
Charlottesville, Virginia, 22903
- Recruiting
The University of Chicago Medical Center (UCMC)
Chicago, Illinois, 60637
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
- Recruiting
Karmanos Cancer Institute
Detroit, Michigan, 48201 2013
- Recruiting
Virginia Cancer Specialists
Fairfax, Virginia, 22031
- Completed
University of California at San Diego Moores Cancer Center
La Jolla, California, 92093
- Recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
- Recruiting
Yale Cancer Center
New Haven, Connecticut, 06520
- Recruiting
University of Utah Huntsman Cancer Institute
Salt Lake City, Utah, 84112
- Recruiting
Washington University School Of Medicine
St Louis, Missouri, 63110
United Kingdom7 sites, 6 recruiting
- Recruiting
Addenbrooke's Hospital
Cambridge, CB2 0QQ
- Recruiting
The Royal Surrey County Hospital NHS Foundation Trust
Guildford, GU2 7XX
- Recruiting
Royal Marsden Hospital (Sutton)
London, SM2 5PT
- Recruiting
Royal Marsden Hospital
London, SW3 6JJ
- Completed
Imperial College London and Imperial College Healthcare NHS Trust
London, W12 0HS
- Recruiting
University College London Hospitals
London, W1T 7HA
- Recruiting
The Christie Nhs Foundation Trust
Manchester, M20 4BX
China6 sites, 4 recruiting
- Completed
Beijing Cancer Hospital of Peking University
Beijing, 100142
- Recruiting
West China School of Medicine/West China Hospital, Sichuan University
Cheng Du Shi, 610041
- Completed
Linyi Cancer Hospital
Linyi, 276002
- Recruiting
Fudan Cancer Hospital
Shanghai, 200032
- Recruiting
Shanghai East Hospital
Shanghai, 200120
- Recruiting
Union Hospital Tongji Medical College of Huazhong University of Science and Technology
Wuhan, 430022
France5 sites, 5 recruiting
- Recruiting
Institut Sainte Catherine
Avignon, 84918
- Recruiting
Centre Oscar Lambret
Lille, 59000
- Recruiting
CHU Nantes
Nantes, 44000
- Recruiting
Institut Curie
Paris, 75248
- Recruiting
Gustave Roussy
Villejuif, 94805
Taiwan5 sites, 5 recruiting
- Recruiting
Changhua Christian Hospital
Changhua, 500
- Recruiting
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 833
- Recruiting
National Taiwan University Hospital
Taipei, 100
- Recruiting
Taipei Veterans General Hospital
Taipei, 112
- Recruiting
Linkou Chang Gung Memorial Hospital
Taoyuan, 33382
South Korea4 sites, 4 recruiting
- Recruiting
Seoul National University Hospital
Seoul, 03080
- Recruiting
Severance Hospital Yonsei University Health System
Seoul, 03722
- Recruiting
Asan Medical Center
Seoul, 05505
- Recruiting
Samsung Medical Center
Seoul, 06351
Spain4 sites, 4 recruiting
- Recruiting
Hosp Univ Vall D Hebron
Barcelona, 08035
- Recruiting
Inst. Cat. Doncologia-H Duran I Reynals
Barcelona, 08908
- Recruiting
Hosp. Univ. Ramon Y Cajal
Madrid, 28034
- Recruiting
Hosp. Univ. 12 de Octubre
Madrid, 28041
Germany3 sites, 2 recruiting
- Recruiting
Universitaetsklinikum Essen
Essen, 45147
- Completed
Universitaetsklinikum Leipzig
Leipzig, 04103
- Recruiting
Klinikum der Landeshauptstadt Stuttgart
Stuttgart, 70174
Poland3 sites, 3 recruiting
- Recruiting
Uniwersyteckie Centrum Kliniczne
Gdansk, 80 214
- Recruiting
Centrum Onkologii Instytut im M Sklodowskiej Curie Oddzial w Gliwicach
Gliwice, 44-102
- Recruiting
Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
Warsaw, 02 781
Japan2 sites, 2 recruiting
- Recruiting
Aichi Cancer Center
Nagoya, 464-8681
- Recruiting
Tokyo Medical University Hospital
Tokyo, 160-0023
Malaysia2 sites, 2 recruiting
- Recruiting
Pantai Hospital Kuala Lumpur
Kuala Lumpur, 59100
- Recruiting
University Malaya Medical Centre
Kuala Lumpur, 59100
About this study
Official title: 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).
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Being tested
- Amivantamab, Pembrolizumab, Paclitaxel, Carboplatin
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmivantamabBiological
Also called JNJ-61186372
Amivantamab will be administered subcutaneously.
PembrolizumabBiological
Also called KEYTRUDA
Pembrolizumab will be administered intravenously.
PaclitaxelDrug
Also called TAXOL
Paclitaxel will be administered intravenously.
CarboplatinDrug
Also called PARAPLATIN
Carboplatin will be administered intravenously.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Amivantamab Monotherapy (Dose Expansion) | Experimental | 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. Receives: Biological: Amivantamab |
| Cohort 2: Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in) | Experimental | 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). Receives: Biological: Amivantamab; Biological: Pembrolizumab |
| Cohort 3A (Dose Confirmation): Amivantamab + Paclitaxel | Experimental | 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. Receives: Biological: Amivantamab; Drug: Paclitaxel |
| Cohort 3B (Dose Expansion): Amivantamab + Paclitaxel | Experimental | 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. Receives: Biological: Amivantamab; Drug: Paclitaxel |
| Cohort 4: Amivantamab Monotherapy | Experimental | 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. Receives: Biological: Amivantamab |
| Cohort 5: Pembrolizumab + Amivantamab + Carboplatin (Dose Expansion) | Experimental | 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. Receives: Biological: Amivantamab; Biological: Pembrolizumab; Drug: Carboplatin |
| Cohort 6: Amivantamab + Pembrolizumab | Experimental | 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. Receives: Biological: Amivantamab; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 2 years and 1 month
Cohort 6: Major Pathologic Response (MPR)
The participants who achieve MPR at the time of surgery.
Measured: 2 years and 2 months
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 2 years and 1 month
Cohort 1 and 4: Maximum Observed Serum Concentration (Cmax) of Amivantamab
Cmax is defined as maximum observed serum concentration of amivantamab.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Predose up to 168 hours post dose on Day 1
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.
Measured: 2 years and 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2024
- Study start22 Apr 2024
- Primary completion27 Dec 2032 (estimated)
- Study completion28 Jul 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Squamous Cell Carcinoma of Head and NeckStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 287 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06385080
- Sponsor's protocol ID
- 61186372HNC2002
- Other IDs
- 61186372HNC2002, 2023-508418-40-00, 2023
- Acronym
- OrigAMI-4
- Status last verified
- Nov 2026
- First submitted
- 23 Apr 2024
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Burtness B, Rosenberg AJ, Calderon B, Lim SM, Yang MH, Li SH, Kadowaki S, Swiecicki PL, Geiger JL, Ince W, Hahn D, Guo Y, Adkins D, Metcalf R, Ahn MJ, Sukari A, Brana I, Keam B, Tanaka H, Sheth S, Oliva M, Lyu X, Curtin JC, Toyoizumi K, Xie J, Wade M, Diorio B, Kapoor A, Yilmaz E, Baig M, Kim P, Verheijen RB, Shah S, Harrington KJ; OrigAMI-4 Cohort 1 Investigators. 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. J Clin Oncol. 2026 May 31:JCO2601042. doi: 10.1200/JCO-26-01042. Online ahead of print.
PubMed 42218660
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06385080
- Acronym / sponsor ID
- OrigAMI-4 / 61186372HNC2002
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 287 participants (estimated)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 22 Apr 2024 (actual)
- Primary completion
- 27 Dec 2032 (estimated)
- Study completion
- 28 Jul 2033 (estimated)
- First posted
- 25 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Amivantamab Monotherapy (Dose Expansion) | Experimental | Biological: AmivantamabParticipants 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) | Experimental | Biological: Amivantamab, Biological: PembrolizumabParticipants 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 | Experimental | Biological: Amivantamab, Drug: PaclitaxelParticipants 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 | Experimental | Biological: Amivantamab, Drug: PaclitaxelParticipants 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 | Experimental | Biological: AmivantamabParticipants 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) | Experimental | Biological: Amivantamab, Biological: Pembrolizumab, Drug: CarboplatinParticipants 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 | Experimental | Biological: Amivantamab, Biological: PembrolizumabParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmivantamabAlso: JNJ-61186372Amivantamab will be administered subcutaneously. | Biological | Cohort 1: Amivantamab Monotherapy (Dose Expansion), Cohort 2: Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in), Cohort 3A (Dose Confirmation): Amivantamab + Paclitaxel, Cohort 3B (Dose Expansion): Amivantamab + Paclitaxel, Cohort 4: Amivantamab Monotherapy, Cohort 5: Pembrolizumab + Amivantamab + Carboplatin (Dose Expansion), Cohort 6: Amivantamab + Pembrolizumab |
| PembrolizumabAlso: KEYTRUDAPembrolizumab will be administered intravenously. | Biological | Cohort 2: Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in), Cohort 5: Pembrolizumab + Amivantamab + Carboplatin (Dose Expansion), Cohort 6: Amivantamab + Pembrolizumab |
| PaclitaxelAlso: TAXOLPaclitaxel will be administered intravenously. | Drug | Cohort 3A (Dose Confirmation): Amivantamab + Paclitaxel, Cohort 3B (Dose Expansion): Amivantamab + Paclitaxel |
| CarboplatinAlso: PARAPLATINCarboplatin will be administered intravenously. | Drug | Cohort 5: Pembrolizumab + Amivantamab + Carboplatin (Dose Expansion) |
Primary outcome
Cohorts 1, 2, 3B, 4 and 5: Objective Response Rate
Time frame: 2 years and 2 months
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.
Cohort 3A: Number of Participants With Dose-limiting Toxicities (DLT)
Time frame: Up to 21 days
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.
Cohort 3A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Severity
Time frame: 2 years and 1 month
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.
Cohort 6: Major Pathologic Response (MPR)
Time frame: 2 years and 2 months
The participants who achieve MPR at the time of surgery.
12 secondary outcomes
Cohorts 1, 2, 3B, 4 and 5: Duration of Response (DoR)
Time frame: 2 years and 2 months
Cohorts 1, 2, 3B, 4 and 5: Clinical Benefit Rate (CBR)
Time frame: 2 years and 2 months
Cohorts 1, 2, 3B, 4 and 5: Progression-free Survival (PFS)
Time frame: 2 years and 2 months
Cohorts 1, 2, 3B, 4, 5 and 6: Overall Survival (OS)
Time frame: 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
Time frame: 2 years and 1 month
Cohort 1 and 4: Maximum Observed Serum Concentration (Cmax) of Amivantamab
Time frame: Predose up to 168 hours post dose on Day 1
Cohort 1 and 4: Time to Maximum Observed Serum Concentration (Tmax) of Amivantamab
Time frame: 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
Time frame: 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
Time frame: Predose up to 168 hours post dose on Day 1
Cohort 1 and 4: Trough Serum Concentration (Ctrough) of Amivantamab
Time frame: Predose up to 168 hours post dose on Day 1
Cohort 1 and 4: Accumulation Ratio (R) of Amivantamab
Time frame: Predose up to 168 hours post dose on Day 1
Cohort 6: Event-Free Survival (EFS)
Time frame: 2 years and 2 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Derived from this study: PubMed 42218660Burtness B, Rosenberg AJ, Calderon B, Lim SM, Yang MH, Li SH, Kadowaki S, Swiecicki PL, Geiger JL, Ince W, Hahn D, Guo Y, Adkins D, Metcalf R, Ahn MJ, Sukari A, Brana I, Keam B, Tanaka H, Sheth S, Oliva M, Lyu X, Curtin JC, Toyoizumi K, Xie J, Wade M, Diorio B, Kapoor A, Yilmaz E, Baig M, Kim P, Verheijen RB, Shah S, Harrington KJ; OrigAMI-4 Cohort 1 Investigators. 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. J Clin Oncol. 2026 May 31:JCO2601042. doi: 10.1200/JCO-26-01042. Online ahead of print.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
56 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Amivantamab, Pembrolizumab and Paclitaxel in people with Squamous Cell Carcinoma of Head and Neck, run by Janssen Research & Development, LLC at 56 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in United States, United Kingdom, China, France, Taiwan and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Contact (844-434-4210, Participate-In-This-Study1@its.jnj.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cohorts 1, 2, 3B, 4 and 5: Objective Response Rate (time frame: 2 years and 2 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06385080, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.