NCT06385080 · Janssen Research & Development, LLC
A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Recurrent/Metastatic Head and Neck Cancer
(OrigAMI-4)
What this study is about
The purpose of this study is to determine safety and preliminary effectiveness of amivantamab treatment given alone, 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.
View original scientific description
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.
Interventions
BIOLOGICAL
Amivantamab
Amivantamab will be administered subcutaneously.
BIOLOGICAL
Pembrolizumab
Pembrolizumab will be administered intravenously.
DRUG
Paclitaxel
Paclitaxel will be administered intravenously.
DRUG
Carboplatin
Carboplatin will be administered intravenously.
Primary outcome measures
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
Where
- La Jolla, California
- Aurora, Colorado
- New Haven, Connecticut
- Chicago, Illinois
- Baltimore, Maryland
- Boston, Massachusetts
- Ann Arbor, Michigan
- Detroit, Michigan
- St Louis, Missouri
- New Brunswick, New Jersey
- Chapel Hill, North Carolina
- Cleveland, Ohio
And 3 more locations — see the full list below.
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Sep 25, 2026 · Source of record for eligibility and locations