Recurrent/metastatic head and neck squamous cell carcinoma Cancer
Conditions
Interventions
The purpose of this study is to compare anti-tumour activity of amivantamab in addition to pembrolizumab and carboplatin versus pembrolizumab, 5 fluorouracil (FU), and platinum therapy (carboplatin or
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Be at least 18 years of age. 2. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 3. Have histologically or cytologically confirmed recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) that is considered incurable by local therapies and meets protocol specified criteria for location and testing. 4. Be treatment-naïve for systemic therapy in the R/M setting, as per protool specified criteria. 5. Have measurable disease according to RECIST v1.1. If only one measurable lesion exists, it may be used for the screening biopsy as long as baseline tumour assessment scans are performed 7 or more days after the biopsyand if lesion remains acceptable as a target lesion after that time. Tumour lesions situated in a previously irradiated area are considered measurable if progression following radiation has been demonstrated in such lesions. 6. Consent to a screening biopsy or provide archival tissue sample per protocol-defined specifications. Participants must have a screening biopsy within 28 days prior to day 1 of the first treatment cycle, or archival tissue that was obtained within 6 months of diagnosis of R/M disease. 7. While on study treatment and for 10 months after the last dose of study treatment, a participant must: Not breastfeed or be pregnant; Not donate gametes (i.e., eggs or sperm) or freeze for future use for the purposes of assisted reproduction; Wear an external condom; If of childbearing potential, participant have a negative highly sensitive serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further pregnancy tests, and practice at least 1 highly effective method of contraception; If a participant’s partner is of childbearing potential, the partner must practice a highly effective method of contraception unless the participant is vasectomised. 8. Must sign an Informed Consent Form (ICF) indicating that the participant understands the purpose and procedures required for the study. 9. Must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
Exclusion criteria
Exclusion criteria: 1. Has an uncontrolled illness. 2. Has untreated brain metastases or history of known presence of leptomeningeal disease. 3. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis/pulmonary fibrosis, has current ILD/pneumonitis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening. 4. Has a history of clinically significant cardiovascular disease. 5. Renal function as specified in the study protocol. 6. Hepatic function as specified in the study protocol. 7. Haematological values as specified in the study protocol. 8. Thyroid function laboratory values not within the normal range. 9. Active hepatitis of infectious origin. 10. Current or chronic history of non-infectious liver disease. 11. Have a prior malignancy (other than the disease under study) in which its natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s). 12. Has known allergies, hypersensitivity, contraindications, or intolerance to excipients of any of the study treatments. 13. Has, or will have, any of the following: a. An invasive operative procedure with entry into a body cavity, including feeding tube placement and tracheostomy, within 4 weeks or without complete recovery before the first administration of study treatment. b. Significant traumatic injury within 3 weeks before the start of the first administration of study treatment. c. Expected major surgery while the investigational agent is being administered, or within 6 months after the last dose of study treatment. 14. Taken any disallowed therapies including immunosuppressive medications within 7 days prior to the first administration of study treatment. 15. 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 specified exclusions. 16. Use of live or live attenuated vaccines during study treatment, within 30 days prior to the first dose of study treatment. 17. Requires prohibited medication that cannot be discontinued, substituted, or temporarily interrupted during the study. 18. Has had radiation therapy within 2 weeks before the first administration of study treatment. 19. Has used an invasive investigational medical device or received an investigational drug (including investigational vaccines) within 6 weeks before the planned first dose of study treatment, or is currently enrolled in an investigational study, or has used investigational anti-cancer therapy within 6 months before the planned first dose of study treatment. 20. HIV-positive participants are only eligible if they meet all the protocol specific clinical requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival (OS) and objective response rate (ORR; using RECIST v1.1) as assessed by Blinded Independent Central Review (BICR). OS is defined as the time from the date of randomisation to the date of death due to any cause. ORR is defined as the proportion of randomised participants achieving a confirmed best overall response (BOR) or partial response (PR) or complete response (CR) by BICR using RECIST v1.1 criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Progression-free survival is measured using RECIST v1.1 as assessed by blinded independent central review (BICR) at baseline and at scheduled tumour assessments throughout the study until disease progression or death 2. Duration of response is measured using RECIST v1.1 as assessed by BICR from the date of first documented response until disease progression or death 3. Objective response rate is measured using RECIST v1.1 as assessed by the investigator at baseline and at scheduled tumour assessments throughout the study 4. Incidence and severity of treatment-emergent adverse events and laboratory abnormalities are measured using CTCAE v5.0 and standard laboratory tests at baseline and throughout the treatment and follow-up periods 5. Proportion of participants with improved or stable symptoms relative to baseline is measured using the symptom scales of the EORTC QLQ-HN43 and EORTC QLQ-C30 at baseline and at scheduled PRO assessment timepoints during treatment and follow-up 6. Change from baseline in functioning and overall health-related quality of life is measured using the functioning and global health status scales of the EORTC QLQ-C30 at baseline and at scheduled PRO assessment timepoints during treatment and follow-up 7. Differences between treatment groups in tolerability are measured using the EORTC IL46 tolerability scale at scheduled PRO assessment timepoints during treatment 8. Serum amivantamab concentrations are measured using validated immunoassays at baseline, during treatment at predefined pharmacokinetic sampling timepoints, and at end of treatment 9. Serum anti-amivantamab antibodies are measured using validated immunogenicity assays at baseline, during treatment at predefined sampling timepoints, and at end of treatment | — |
Countries
Australia, Austria, Belgium, Brazil, China, England, France, Germany, Hungary, India, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Romania, Spain, Taiwan, United Kingdom
Contacts
Public ContactJoe Taylor
Outcome results
None listed