Health Condition 1: C00-C14- Malignant neoplasms of lip, oral cavity and pharynx
Conditions
Interventions
Intervention1: Ficerafusp alfa in combination with Pembrolizumab: Dose and Route
Ficerafusp alfa 750 mg or 1500 mg, administered via intravenous (IV) infusion
Pembrolizumab 200 mg, administered via in
Sponsors
Bicara Therapeutics Inc.
IQVIA RDSIndia Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: Subject or legally authorized representative (if applicable) has signed and dated the Informed Consent Form (ICF) prior to initiation of any study-specific procedures and is willing to comply with all study requirements; Subject is 18 years of age or older, or meets the minimum age as per local regulations, whichever is higher, at the time of signing the ICF; Histologically or cytologically confirmed recurrent (R) or metastatic (M) head and neck squamous cell carcinoma (HNSCC); eligible primary tumor sites include oral cavity, hypopharynx, larynx, or oropharynx; subjects with oropharyngeal squamous cell carcinoma (OPSCC) must have documented HPV-negative disease; tumors originating in the nasopharynx or paranasal sinuses are excluded; No prior systemic therapy in the incurable recurrent or metastatic setting; prior systemic therapy given as part of multimodal treatment for locoregionally advanced disease is allowed if completed more than 6 months prior to signing ICF; Subject is willing to provide archival tumor tissue or undergo a pretreatment biopsy if archival tissue is unavailable or insufficient; For subjects with OPSCC: documented HPV-negative status is required based on central testing using Qiagen therascreen HPV Panel RGQ PCR Kit; tumor tissue from excisional, incisional or core biopsy must be provided (fine needle aspirates and bone biopsies are not acceptable); archival tissue is acceptable; fresh biopsy from a non-irradiated or progressing lesion is required if adequate tissue is not available; Subject is eligible for pembrolizumab frontline monotherapy with PD-L1 Combined Positive Score (CPS) 1 or higher determined using PD-L1 IHC 22C3 pharmDx assay (local or central testing); if local results are unavailable, tumor tissue must be provided for central testing to determine eligibility; Subject has at least one measurable lesion as per RECIST version 1.1 assessed by Blinded Independent Central Review (BICR); lesions in previously irradiated areas are acceptable if progression is documented; baseline imaging must be submitted for BICR assessment; ECOG performance status of 0 or 1; Adequate organ function as defined by: absolute neutrophil count (ANC) 1500 per microliter or higher; platelets 100,000 per microliter or higher; hemoglobin 9 grams per deciliter or higher without transfusion within 7 days; creatinine clearance or estimated glomerular filtration rate 30 milliliters per minute or higher; total bilirubin 1.5 times upper limit of normal or less (up to 3 times upper limit of normal for Gilbert syndrome with normal direct bilirubin); AST and ALT 2.5 times upper limit of normal or less or up to 5 times upper limit of normal in subjects with liver metastases; INR, PT, or aPTT 1.5 times upper limit of normal or less unless on anticoagulation therapy within therapeutic range; Women of childbearing potential must have a negative highly sensitive serum pregnancy test within 7 days prior to first dose (urine test acceptable as per local standard of care); Women of childbearing potential must agree to use highly effective contraception, be surgically sterile, or remain abstinent during the study and for 120 days after the last dose and must not donate oocytes during this period; such women are defined as those who are not surgically sterilized and have not been free from menses for more than 1 year; Male subjects must agree to use a condom or rema
Exclusion criteria
Exclusion criteria: 1. Prior systemic therapy in the incurable recurrent or metastatic setting; 2. Disease suitable for local therapy administered with curative intent; 3. Prior treatment with anti-TGF-beta therapy; 4. Prior therapy with an anti-EGFR antibody (except radio-sensitizing agents or multimodal treatment for locoregionally advanced disease); 5. Prior history of Grade 2 or higher intolerance or hypersensitivity reaction to anti-EGFR therapy, murine proteins, or components of ficerafusp alfa, pembrolizumab, or their excipients; 6. Prior neoadjuvant or adjuvant therapy with an immune checkpoint inhibitor completed within 6 months prior to study treatment initiation; 7. Disease progression (radiologically or pathologically confirmed) within 6 months from completion of curative intent systemic therapy for locoregionally advanced HNSCC; 8. Life expectancy of less than 3 months or rapidly progressing disease in the investigator s opinion; 9. Known active central nervous system metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease; subjects with treated central nervous system metastases may be eligible if stable for at least 4 weeks, with no progression on imaging and no steroid requirement for at least 14 days prior to first dose; 10. Subjects at high risk of bleeding, including known bleeding disorders, active major bleeding, or major bleeding episode within 4 weeks prior to enrollment; a major bleeding event includes fatal bleeding, bleeding in critical organs, hemoglobin drop of 2 grams per deciliter or more, or transfusion of 2 or more units of blood; subjects with tumor invasion of major blood vessels, ulceration, fistula, visible carotid artery exposure, or significant hemoptysis within 4 weeks must be excluded; 11. History within 6 months prior to treatment of myocardial infarction, unstable angina, uncontrolled ventricular arrhythmia, major vascular procedures, stroke, or New York Heart Association Class 3 or 4 heart failure; subjects with stable deep vein thrombosis on anticoagulation for at least 3 months may be eligible; 12. Major surgery or palliative radiotherapy within 2 weeks prior to randomization or not adequately recovered from such procedures; 13. Participation in another clinical study or receipt of investigational therapy within 4 weeks or 5 half-lives of prior treatment, whichever is shorter; 14. Active autoimmune disease requiring systemic treatment within the past 2 years; replacement therapies are allowed; 15. Serious systemic infection within 4 weeks prior to first dose or active infection requiring hospitalization or intravenous treatment within 2 weeks prior to first dose; 16. Psychiatric, behavioral, or substance abuse disorders that interfere with study compliance; 17. Active hepatitis B infection not adequately controlled; subjects on antiviral therapy for at least 4 weeks with undetectable viral load may be eligible and must continue treatment; 18. Active hepatitis C infection without completed antiviral therapy or detectable viral load at screening; 19. Known history of human immunodeficiency virus infection; 20. Prior organ transplantation requiring immunosuppression; 21. Additional malignancy within 2 years prior to randomization, except certain treated low-risk cancers (e.g., basal cell carcinoma, in situ cancers, or low-risk
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare efficacy in subjects treated with ficerafusp alfa at the selected OBD in combination with pembrolizumab versus placebo plus pembrolizumabTimepoint: Baseline, every 6 weeks for the first 24 weeks and every 9 to 12 weeks thereafter until disease progression, end of treatment or study completion as per protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| -To compare safety & tolerability of subjects treated with ficerafusp alfa at the selected OBD in combination with pembrolizumab versus placebo plus pembrolizumab. -To further compare efficacy in subjects treated with ficerafusp alfa in combination with pembrolizumab versus placebo plus pembrolizumab. -To evaluate time to deterioration in global health status or quality of life & pain in subjects treated with ficerafusp alfa in combination with pembrolizumab versus placebo plus pembrolizumab.Timepoint: Baseline, continuous monitoring for safety during treatment, tumor assessments every 6 to 12 weeks as per protocol & at disease progression or end of treatment. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, France, Germany, Greece, India, Ireland, Israel, Italy, Malaysia, New Zealand, Poland, Portugal, Republic of Korea, Singapore, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States of America
Contacts
Public ContactShweta Pradhan
IQVIA RDS (India) Private Limited
Outcome results
None listed