Squamous cell carcinoma of the head and neck
Conditions
Interventions
Cohort2:Pembrolizumab + Amivantamab
Cohort3A/3B:Paclitaxel + Amivantamab
Cohort4:Treatment with amivantamab in subjects with HPV-associated HNSCC.
Chort1:Treatment with amivantamab in subjects with HPV-unrelated HNSCC.
Sponsors
Shanghai East Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Be >=18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater) at the time of informed consent. 2.Have histologically or cytologically confirmed R/M HNSCC that is considered incurable by local therapies. Cohorts 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 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 highrisk HPV ISH in tissue (current or archival). c. Participants must provide local testing results of PD-L1 status, if available; 3.Participants must meet the following cohort-specific requirements: Cohort 3A: Dose Confirmation Cohort a. Have evaluable disease (defined as having at least 1 non-target lesion according to RECIST v1.1). If only 1 evaluable lesion exists, it may be used for the screening biopsy as long as baseline tumor assessment scans are performed >=7 days after the biopsy. Tumor lesions situated in a previously irradiated area are considered evaluable if progression following radiation has been demonstrated in such lesions. Cohorts 1, 3B, and 4: Dose Expansion Cohorts b. Have measurable disease according to RECIST v1.1. If only 1 measurable lesion exists, it may be used for the screening biopsy as long as baseline tumor assessment scans are performed >=7 days after the biopsy. Tumor lesions situated in a previously irradiated area are considered measurable if progression following radiation has been demonstrated in such lesions. A lesion that was biopsied during Screening should only be assessed as a target lesion if a post-biopsy imaging is performed >7 days and confirms that it still meets measurability criteria and is amenable to accurate and reproducible measurement. Cohort 2: Dose Expansion Cohort c. Have measurable disease according to RECIST v1.1. If only 1 measurable lesion exists, it may be used for the screening biopsy as long as baseline tumor assessment scans are performed >=7 days after the biopsy. Tumor lesions situated in a previously irradiated area are considered measurable if progression following radiation has been demonstrated in such lesions. 4.If available, provide adequate tumor tissue for a baseline sample following the most recent systemic anticancer therapy. The tissue sample should meet the sample requirements as outlined in the lab manual and should be accompanied with pathology report to review tumor specifications.In addition, participants must meet the following cohort-specific requirements: Cohorts 1, 3A, 3B, and 4: Dose Confirmation and Expansion Cohorts a. The sponsor reserves the right to allocate the final enrollment slots in Cohorts 1 and 3B to ensure that at least 30 participants in Cohort 1 expansion (including at least 10 participants enrolled before the expansion of Cohort 1 via Amendment 2), at least 10 participants in Cohorts 3A and 3B combined, and at least 10 participants in Cohort 4 provide adequate tumor tissue, either based on acceptable archival specimen or a screening biopsy. If a different dose level is used in Cohorts 3A and 3B, tumor tissue samples are required for at le
Exclusion criteria
Exclusion criteria: 1.Uncontrolled illness, including but not limited to (applicable to all participants): a. Diabetes. b. Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to starting study treatment]) or diagnosed or suspected viral infection. c. Active bleeding diathesis. d. Impaired oxygenation requiring continuous oxygen supplementation. e. Psychiatric illness/social situation that would limit compliance with study requirements. Cohort 2: Pembrolizumab + Amivantamab f. Autoimmune disease that has required systemic therapy in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic therapy.g. History of Grade 3 or higher immune-related AEs from prior anticancer therapy or a monoclonal antibody, except for endocrinopathies that are stable on replacement therapies. h. Participant had an allogeneic tissue/solid organ transplant; 2.Medical history of (non-infectious) ILD/pneumonitis/pulmonary fibrosis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening. 3.Known allergies, hypersensitivity, or intolerance to excipients of amivantamab or rHuPH20 (refer to the IB). Cohort 2: Pembrolizumab + Amivantamab Known allergies, hypersensitivity, intolerance, or contraindication to excipients of pembrolizumab (refer to the product label). Cohorts 3A and 3B: Paclitaxel + Amivantamab Known allergies, hypersensitivity, intolerance, or contraindication to excipients of paclitaxel (refer to the product label). 4.Participant has a history of clinically significant cardiovascular disease including, but not limited to the following: Diagnosis of deep vein thrombosis or pulmonary embolism within 8 weeks prior to the first dose of study treatment or any of the following within 6 months prior to the first dose of study treatment: myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary. Prolonged QTcF interval >480 msec or clinically significant cardiac arrhythmia or electrophysiologic disease (eg, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate). Note: Participants with cardiac pacemakers who are clinically stable are eligible. Uncontrolled (persistent) hypertension: systolic blood pressure >180 mm Hg; diastolic blood pressure >100 mm Hg. Congestive heart failure defined as NYHA Class III, IV or Hospitalization for congestive heart failure (any NYHA Class) (NYHA Criteria are provided in the Appendix 10) within 6 months of the first dose of study treatment. Pericarditis/clinically significant pericardial effusion. Myocarditis. 5.Participant has, or will have, any of the following: a. An invasive operative procedure with entry into a body cavity, within 4 weeks or without complete recovery before the first administration of study treatment. Thoracentesis, if needed, and percutaneous biopsy for baseline tumor tissue sample may be done less than 4 weeks prior to the first administration of study treatment, as long as the participant h
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR; | — |
Countries
China
Contacts
Public ContactGuo Ye
Shanghai East Hospital
Outcome results
None listed