The study is an open-label phase I/II clinical trial. The study will enroll patients to receive neoadjuvant SBRT plus 1 or 2 doses of neoadjuvant pembrolizumab with concurrent ficerafusp alfa (4 doses) prior to definitive surgical resection for high-risk, locoregionally advanced HPV-negative head and neck squamous cell carcinoma (HNSCC). Approximately 6 weeks after end of SBRT, patients will undergo standard of care (SOC) surgical resection followed by SOC adjuvant chemoradiation per National Comprehensive Cancer Network (NCCN) guidelines. Adjuvant therapy is not part of this study and therefore is not dictated by study protocol.
Newly diagnosed histologically or cytologically confirmed locally advanced, OPC HPV-negative head and neck squamous cell carcinoma (OPSCC) or HNSCC arising from oral cavity, larynx, or hypopharynx.
Baseline resectable disease per the judgment of the treating surgical oncologist.
T1-2, N1-3 or
T3, any N or
Currently receiving any other investigational agents.
Prior history of grade ≥ 2 intolerance or hypersensitivity reactions to other murine proteins, or the active substances of ficerafusp alfa, pembrolizumab, or any of their excipients.
At higher risk of bleeding, including known bleeding diathesis or current active major bleeding, or recent major bleeding episode (within 4 weeks prior to enrollment).
Any of the following within 6 months prior to starting study treatment: ST-elevation myocardial infarction, severe/unstable angina, uncontrolled cardiac ventricular arrhythmia, coronary/peripheral artery bypass graft or stent, cerebrovascular accident/stroke less than 6 months prior to enrollment, or congestive heart failure. Subjects with deep vein thrombosis who are hemodynamically stable can enroll if they are on a stable dose of anticoagulants for at least 3 months.
Sequential
Hypofractionated Stereotactic Body Radiotherapy (SBRT)
Radiation1-3 fractions given over 1 week as assigned in phase I and as determined to be the maximum tolerated dose (MTD) in phase II
Pembrolizumab
Biological/Vaccine200 mg intravenously (IV) given on Day 1 or Days 1 and 22 as assigned in phase I and as determined to be the maximum tolerated dose (MTD) in phase II.
Ficerafusp alfa
Drug750mg intravenously (IV) on Days 1, 8, 15, and 22.
Phase I only: Maximum tolerated dose (MTD) of SBRT in combination with pembrolizumab plus ficerafusp alfa
The maximum tolerated dose (MTD) is defined as the highest dose level at which 0 or 1 patients of a cohort experience dose-limiting toxicity during the dose limiting toxicity (DLT) window. DLTs are defined in the protocol.
Phase II only: Rate of pathologic complete response (pCR)
Response will be defined according to the systematic pTR system. pTR is defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor). pCR is defined as follows: 100% of sample characterized by tumor necrosis, keratinous debris, and/or giant cells/histiocytes
Phase II only: Number and types of Adverse Events (AEs)
As defined by CTCAE v5.0.
Phase II only: Pathological response rate (PRR)
PRR is categorized as pCR, mPR, and others (pTR-0, pTR-1, pTR-2). Simon's two-stage optimal design will be used for a rate of pCR in phase II. Response will be defined according to the systematic pTR system. pTR is defined as the presence of tumor cell necrosis and keratinous debris with giant cell/histiocytic reaction, quantified as a percentage of the overall tumor bed (area pathologic response/area pathologic response plus viable tumor). pTR is defined as follows: pTR-0: \< 10% of sample characterized by tumor necrosis, keratinous debris, and/or giant cells/histiocytes, pTR-1: 10-49%, pTR-2: 50-89%, pTR-3: 90-99% (also referred to as mPR), and pTR-4: 100% (also referred to as pCR).
Phase II only: Event-free survival (EFS)
EFS is defined as the time from the first date of treatment to the date of disease progression or death, whichever occurs first.
Phase II only: Rate of clinical to pathologic down staging (and extent of surgical plan modifications, if any)
Click on the lead sponsor to view all of their trials.
Washington University School of Medicine
Lead sponsor
Bicara Therapeutics
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
