A Phase 1b/2, Open-label Study of Amivantamab Monotherapy and Amivantamab in Addition to Standard of Care Therapeutic Agents in Participants with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
- Conditions
- Recurrent/Metastatic Head and Neck Squamous Cell CarcinomaTherapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-508418-40-00
- Lead Sponsor
- Janssen Cilag International
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 117
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., 10. Participants are eligible if they have the following lab values: a. AST =3 x ULN (=5 x ULN if liver metastases are present) b. ALT =3 x ULN (=5 x ULN if liver metastases are present) c. Total bilirubin =1.5x ULN, participants with congenital nonhemolytic hyperbilirubinemia such as Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits., 11. 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 =9g/dL. b. Neutrophils =1.5 x 103/µL. c. Platelets =100 x 103/µL., 12. Participants must meet the following cohort-specific requirements: Cohort 2: Pembrolizumab + Amivantamab Thyroid function laboratory values within the normal range., 2. Have histologically or cytologically confirmed R/M HNSCC that is considered incurable by local therapies. 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, 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 and 3B: 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. 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, and 3B: 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 10 participants in Cohort 1, and at least 10 participants in Cohorts 3A and 3B combined provide adequate tumor tissue, eithe
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., 10. Received radiotherapy for palliative purposes within 7 days of the first administration of study treatment., 11. Requires a prohibited medication that cannot be discontinued, substituted, or temporarily interrupted during the study;, 12. Received an investigational treatment (including investigational vaccines, but not including anticancer therapy) or used an invasive investigational medical device within 6 weeks before the planned first dose of study treatment., 13. Cohort 2: Pembrolizumab + Amivantamab Prohibited immunosuppressive medication use within 7 days prior to the first administration of study treatment., 14. Cohort 2: Pembrolizumab + Amivantamab Participant has received a live or live attenuated vaccine within 30 days prior to the first dose of study drug. Vaccines approved or authorized for emergency use (eg, COVID-19) and non-live vaccines (eg, influenza) are allowed., 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 uncont
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method