Amivantamab: Amivantamab will be administered subcutaneously.
Pembrolizumab: Pembrolizumab will be administered intravenously.
Paclitaxel: Paclitaxel will be administered intravenously.
Carboplatin: Carboplatin will be administered intravenously.
Study 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).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
Cohorts 1, 2, 3B, 4 and 5: Objective Response Rate — 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) — 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 — 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) — 2 years and 2 months The participants who achieve MPR at the time of surgery.
Trial sites (56)
Facility
City
Region
Status
University of California at San Diego Moores Cancer Center
La Jolla
California
Completed
University of Colorado Denver Anschultz Medical Campus
Aurora
Colorado
Recruiting
Yale Cancer Center
New Haven
Connecticut
Recruiting
The University of Chicago Medical Center (UCMC)
Chicago
Illinois
Recruiting
University of Maryland School of Medicine
Baltimore
Maryland
Recruiting
Dana Farber Cancer Institute
Boston
Massachusetts
Recruiting
University of Michigan Rogel Cancer Center
Ann Arbor
Michigan
Recruiting
Karmanos Cancer Institute
Detroit
Michigan
Recruiting
Washington University School Of Medicine
St Louis
Missouri
Recruiting
Rutgers Cancer Institute of New Jersey
New Brunswick
New Jersey
Recruiting
University of North Carolina at Chapel Hill
Chapel Hill
North Carolina
Recruiting
Cleveland Clinic
Cleveland
Ohio
Recruiting
University of Utah Huntsman Cancer Institute
Salt Lake City
Utah
Recruiting
University of Virginia
Charlottesville
Virginia
Recruiting
Virginia Cancer Specialists
Fairfax
Virginia
Recruiting
Beijing Cancer Hospital of Peking University
Beijing
China
Completed
West China School of Medicine/West China Hospital, Sichuan University
Cheng Du Shi
China
Recruiting
Linyi Cancer Hospital
Linyi
China
Completed
Fudan Cancer Hospital
Shanghai
China
Recruiting
Shanghai East Hospital
Shanghai
China
Recruiting
Union Hospital Tongji Medical College of Huazhong University of Science and Technology
Wuhan
China
Recruiting
Institut Sainte Catherine
Avignon
France
Recruiting
Centre Oscar Lambret
Lille
France
Recruiting
CHU Nantes
Nantes
France
Recruiting
Institut Curie
Paris
France
Recruiting
Gustave Roussy
Villejuif
France
Recruiting
Universitaetsklinikum Essen
Essen
Germany
Recruiting
Universitaetsklinikum Leipzig
Leipzig
Germany
Completed
Klinikum der Landeshauptstadt Stuttgart
Stuttgart
Germany
Recruiting
Aichi Cancer Center
Nagoya
Japan
Recruiting
Tokyo Medical University Hospital
Tokyo
Japan
Recruiting
Pantai Hospital Kuala Lumpur
Kuala Lumpur
Malaysia
Recruiting
University Malaya Medical Centre
Kuala Lumpur
Malaysia
Recruiting
Uniwersyteckie Centrum Kliniczne
Gdansk
Poland
Recruiting
Centrum Onkologii Instytut im M Sklodowskiej Curie Oddzial w Gliwicach
Gliwice
Poland
Recruiting
Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
Warsaw
Poland
Recruiting
Seoul National University Hospital
Seoul
South Korea
Recruiting
Severance Hospital Yonsei University Health System
Seoul
South Korea
Recruiting
Asan Medical Center
Seoul
South Korea
Recruiting
Samsung Medical Center
Seoul
South Korea
Recruiting
+ 16 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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