Recruiting
Phase 1/2
A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Head and Neck Cancer
Condition(s) studied
Squamous Cell Carcinoma of Head and Neck
Investigational drug(s) / intervention(s)
AmivantamabPembrolizumabPaclitaxelCarboplatin
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
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.
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