Squamous Cell Carcinoma of Head and Neck
Conditions
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).
Interventions
BIOLOGICALAmivantamab
Amivantamab will be administered subcutaneously.
BIOLOGICALPembrolizumab
Pembrolizumab will be administered intravenously.
DRUGPaclitaxel
Paclitaxel will be administered intravenously.
DRUGCarboplatin
Carboplatin will be administered intravenously.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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, 5 and 6: 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, 5 and 6: 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. |
| Cohort 6: Event-Free Survival (EFS) | 2 years and 2 months | EFS is defined as the time from the first administration of study treatment until the date of radiographic disease progression, local or distant progression or recurrence as assessed with imaging or biopsy as indicated, or death due to any cause. |
Countries
China, France, Germany, Japan, Malaysia, Poland, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed