Recruiting

Phase 1

Phase 2

AmivantamabA Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Head and Neck Cancer

Sponsor:

Janssen Research & Development, LLC

Code:

NCT06385080

Conditions

Squamous Cell Carcinoma of Head and Neck

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Amivantamab

Pembrolizumab

Paclitaxel

Carboplatin

Study Details

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).

Conditions

Squamous Cell Carcinoma of Head and Neck

Study ID

NCT06385080

Start date

Apr 22, 2024

Status verified date

Aug, 2026

Completion date

Jul 28, 2033

Anticipated

Primary completion date

Dec 27, 2032

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

287 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

experimental: Cohort 2: Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in)

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.

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.

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.

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.

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.

Interventions

Amivantamab

Amivantamab will be administered subcutaneously.

Pembrolizumab

Pembrolizumab will be administered intravenously.

Paclitaxel

Paclitaxel will be administered intravenously.

Carboplatin

Carboplatin will be administered intravenously.

Primary outcome measure

Cohorts 1, 2, 3B, 4 and 5: Objective Response Rate [ Time Frame: 2 years and 2 months ]
Cohort 3A: Number of Participants With Dose-limiting Toxicities (DLT) [ Time Frame: Up to 21 days ]
Cohort 3A: Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Severity [ Time Frame: 2 years and 1 month ]
Cohort 6: Major Pathologic Response (MPR) [ Time Frame: 2 years and 2 months ]

Central Contacts and Locations

Central contacts

Study Contact

844-434-4210 Participate-In-This-Study1@its.jnj.com

Locations

University of Colorado Denver Anschultz Medical Campus

Recruiting

Aurora, Colorado, United States, 80045

Yale Cancer Center

Recruiting

New Haven, Connecticut, United States, 06520

The University of Chicago Medical Center (UCMC)

Recruiting

Chicago, Illinois, United States, 60637

University of Maryland School of Medicine

Recruiting

Baltimore, Maryland, United States, 21201

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02115

University of Michigan Rogel Cancer Center

Recruiting

Ann Arbor, Michigan, United States, 48109

Karmanos Cancer Institute

Recruiting

Detroit, Michigan, United States, 48201 2013

Washington University School Of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Rutgers Cancer Institute of New Jersey

Recruiting

New Brunswick, New Jersey, United States, 08901

University of North Carolina at Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 27599

Cleveland Clinic

Recruiting

Cleveland, Ohio, United States, 44195

University of Utah Huntsman Cancer Institute

Recruiting

Salt Lake City, Utah, United States, 84112

University of Virginia

Recruiting

Charlottesville, Virginia, United States, 22903

Virginia Cancer Specialists

Recruiting

Fairfax, Virginia, United States, 22031

More Information

Sponsor

Janssen Research & Development, LLC

Last update posted

Aug 28, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Janssen Research & Development, LLC on 2026-08-28.