A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Recurrent/Metastatic Head and Neck Cancer
- Conditions
- Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
- Interventions
- Registration Number
- NCT06385080
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 247
- Have histologically or cytologically confirmed recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) that is considered incurable by local therapies. 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: (a) Patients must have primary tumor location in oropharynx. Unknown primary tumors are not included (b) 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) (c) Participants must provide local testing results of PD-L1 status, if available; Cohort 5 (a) The eligible primary tumor locations are the oropharynx, oral cavity, hypopharynx, or larynx; (b) 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; (c) Participants must provide local testing results of PD-L1 status
- Participants in Cohorts 1, 2, 3B, 4 and 5 must have measurable disease according to RECIST version 1.1. Participants in Cohort 3A must have evaluable disease (defined as having at least 1 non-target lesion according to RECIST version 1.1
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1: Amivantamab Monotherapy (Dose Expansion) Amivantamab 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. Cohort 2: Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in) Amivantamab 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 pembrolizumab 200 mg q3w (on Day 1 of each 21-day cycle). Cohort 2: Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in) 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 onwards, along with intravenous injection of pembrolizumab 200 mg q3w (on Day 1 of each 21-day cycle). Cohort 3A (Dose Confirmation): Amivantamab + Paclitaxel Amivantamab 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. Cohort 3A (Dose Confirmation): Amivantamab + Paclitaxel 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. Cohort 3B (Dose Expansion): Amivantamab + Paclitaxel Amivantamab 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. Cohort 3B (Dose Expansion): Amivantamab + Paclitaxel 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. Cohort 4: Amivantamab Monotherapy Amivantamab 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. Cohort 5: Pembrolizumab + Amivantamab + Carboplatin (Dose Expansion) Amivantamab 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. Cohort 5: Pembrolizumab + Amivantamab + Carboplatin (Dose Expansion) 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 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 5: Pembrolizumab + Amivantamab + Carboplatin (Dose Expansion) Carboplatin 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.
- Primary Outcome Measures
Name Time Method 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.
- Secondary Outcome Measures
Name Time Method Cohorts 1, 2, 3B, 4 and 5: Duration of Response (DoR) 2 years and 2 months 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.
Cohorts 1, 2, 3B, 4 and 5: Clinical Benefit Rate (CBR) 2 years and 2 months 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.
Cohorts 1, 2, 3B, 4 and 5: Progression-free Survival (PFS) 2 years and 2 months 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.
Cohorts 1, 2, 3B, 4 and 5: Overall Survival (OS) 2 years and 2 months OS is defined as the time from the first administration of study treatment until the date of death due to any cause.
Cohorts 1, 2, 3B, 4 and 5: 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 events.
Cohort 1 and 4: Maximum Observed Serum Concentration (Cmax) of Amivantamab Predose up to 168 hours post dose on Day 1 Cmax is defined as maximum observed serum concentration of amivantamab.
Cohort 1 and 4: Time to Maximum Observed Serum Concentration (Tmax) of Amivantamab Predose up to 168 hours post dose on Day 1 Tmax is defined as time to maximum observed serum concentration of amivantamab.
Cohort 1 and 4: Area Under the Serum Concentration Curve Verses Time Curve From Time t1 to t2 (AUC[t1-t2]) of Amivantamab Predose up to 168 hours post dose on Day 1 AUC(t1-t2) is defined as area under the serum concentration versus time curve from time t1 to time t2 of amivantamab.
Cohort 1 and 4: Area Under the Curve From Time Zero to tau (AUC[0-tau]) of Amivantamab Predose up to 168 hours post dose on Day 1 AUC(0-tau) is defined as area under the curve from time 0 to tau hours of amivantamab.
Cohort 1 and 4: Trough Serum Concentration (Ctrough) of Amivantamab Predose up to 168 hours post dose on Day 1 Ctrough is defined as the serum concentration of amivantamab.
Cohort 1 and 4: Accumulation Ratio (R) of Amivantamab Predose up to 168 hours post dose on Day 1 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.
Trial Locations
- Locations (51)
Inst. Cat. Doncologia-H Duran I Reynals
🇪🇸Barcelona, Spain
Hosp. Univ. Ramon Y Cajal
🇪🇸Madrid, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
University of California at San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
University of Colorado Denver Anschultz Medical Campus
🇺🇸Aurora, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
The University of Chicago Medical Center (UCMC)
🇺🇸Chicago, Illinois, United States
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
University of Michigan Rogel Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Utah Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Beijing Cancer Hospital of Peking University
🇨🇳Beijing, China
West China School of Medicine/West China Hospital, Sichuan University
🇨🇳Cheng Du Shi, China
Shanghai East Hospital
🇨🇳Shanghai, China
Institut Sainte Catherine
🇫🇷Avignon Cedex 9, France
Centre Oscar Lambret
🇫🇷Lille, France
CHU Nantes
🇫🇷Nantes Cedex 1, France
Institut Curie
🇫🇷PARIS Cedex 5, France
Gustave Roussy
🇫🇷Villejuif Cedex, France
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Klinikum der Landeshauptstadt Stuttgart
🇩🇪Stuttgart, Germany
Aichi Cancer Center
🇯🇵Nagoya, Japan
Tokyo Medical University Hospital
🇯🇵Tokyo, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Pantai Hospital Kuala Lumpur
🇲🇾Kuala Lumpur, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Centrum Onkologii Instytut im M Sklodowskiej Curie Oddzial w Gliwicach
🇵🇱Gliwice, Poland
Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
🇵🇱Warszawa, Poland
Hosp Univ Vall D Hebron
🇪🇸Barcelona, Spain
Changhua Christian Hospital
🇨🇳ChangHua, Taiwan
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Linkou Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
The Royal Surrey County Hospital NHS Foundation Trust
🇬🇧Guildford, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Imperial College London and Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
University College London Hospitals
🇬🇧London, United Kingdom
The Christie Nhs Foundation Trust
🇬🇧Manchester, United Kingdom