Ficerafusp Alfa, Pembrolizumab, and Stereotactic Body Radiotherapy (SBRT) for Head and Neck Squamous Cell Carcinoma (HNSCC)
Phase I/II Trial of Neoadjuvant Combination of Ficerafusp Alfa, Pembrolizumab, and SBRT for Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)
1 other identifier
interventional
45
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jun 2026
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 20, 2026
CompletedFirst Posted
Study publicly available on registry
April 27, 2026
CompletedStudy Start
First participant enrolled
June 30, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2028
Study Completion
Last participant's last visit for all outcomes
August 31, 2033
April 27, 2026
April 1, 2026
2.2 years
April 20, 2026
April 20, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
From start of treatment until date of surgery (total estimated time of 7 weeks)
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
At the time of surgery (estimated to be week 7)
Secondary Outcomes (5)
Phase II only: Number and types of Adverse Events (AEs)
From start of treatment through 5 years after completion of treatment (estimated to be 5 years and 2 months)
Phase II only: Pathological response rate (PRR)
At time of surgery (estimated to be week 7)
Phase II only: Event-free survival (EFS)
From start of treatment through 5 years after completion of treatment (estimated to be 5 years and 2 months)
Phase II only: Rate of clinical to pathologic down staging (and extent of surgical plan modifications, if any)
At time of surgery (estimated to be week 7)
Phase II only: Overall survival (OS)
From start of treatment through 5 years after completion of treatment (estimated to be 5 years and 2 months)
Study Arms (5)
Phase 1 Dose Level 1: Dose De-Escalation Neoadjuvant SBRT and pembrolizumab plus ficerafusp alfa
EXPERIMENTALTreatment during the Phase 1 Level 1 consists of Stereotactic Body Radiotherapy (SBRT) at 8 Gy x 3 fractions over one week (given on Days 1, 3, and 5), 2 doses of neoadjuvant pembrolizumab at 200 mg (given on D1 and D22), and 4 weekly doses of ficerafusp alfa at 750 mg (given on D1, D8, D15, and D22). Six weeks after end of SBRT, patients will undergo standard of care (SOC) surgical resection, or biopsy for patients who do not undergo resection, followed by standard of care (SOC) adjuvant chemoradiation per National Comprehensive Cancer Network (NCCN) guidelines.
Phase 1 Dose Level -1: Dose De-Escalation Neoadjuvant SBRT and pembrolizumab plus ficerafusp alfa
EXPERIMENTALTreatment during the Phase 1 Level -1 consists of Stereotactic Body Radiotherapy (SBRT) at 8 Gy x 3 fractions over one week (given on Days 1, 3, and 5), 1 dose of neoadjuvant pembrolizumab at 200 mg (given on D1), and 4 weekly doses of ficerafusp alfa at 750 mg (given on D1, D8, D15, and D22). Six weeks after end of SBRT, patients will undergo standard of care (SOC) surgical resection, or biopsy for patients who do not undergo resection, followed by standard of care (SOC) adjuvant chemoradiation per National Comprehensive Cancer Network (NCCN) guidelines.
Phase 1 Dose Level -2: Dose De-Escalation Neoadjuvant SBRT and pembrolizumab plus ficerafusp alfa
EXPERIMENTALTreatment during the Phase 1 Level -2 consists of Stereotactic Body Radiotherapy (SBRT) at 8 Gy x 3 fractions over one week (given on Days 1 and 4), 1 dose of neoadjuvant pembrolizumab at 200 mg (given on D1), and 4 weekly doses of ficerafusp alfa at 750 mg (given on D1, D8, D15, and D22). Six weeks after end of SBRT, patients will undergo standard of care (SOC) surgical resection, or biopsy for patients who do not undergo resection, followed by standard of care (SOC) adjuvant chemoradiation per National Comprehensive Cancer Network (NCCN) guidelines.
Phase 1 Dose Level -3: Dose De-Escalation Neoadjuvant SBRT and pembrolizumab plus ficerafusp alfa
EXPERIMENTALTreatment during the Phase 1 Level -3 consists of Stereotactic Body Radiotherapy (SBRT) at 8 Gy x 3 fractions over one week (given on Day 1), 1 dose of neoadjuvant pembrolizumab at 200 mg (given on D1), and 4 weekly doses of ficerafusp alfa at 750 mg (given on D1, D8, D15, and D22). Six weeks after end of SBRT, patients will undergo standard of care (SOC) surgical resection, or biopsy for patients who do not undergo resection, followed by standard of care (SOC) adjuvant chemoradiation per National Comprehensive Cancer Network (NCCN) guidelines.
Phase 2: Maximum Tolerable Dose (MTD) Neoadjuvant SBRT and pembrolizumab plus ficerafusp alfa
EXPERIMENTALTreatment consists of SBRT beginning on D1 at the dose and number of fractions established in phase I, neoadjuvant pembrolizumab 200 mg at the number of doses established in phase I, and 4 weekly doses of ficerafusp alfa 750 mg (given on D1, D8, D15, and D22). Six weeks after end of SBRT, patients will undergo standard of care (SOC) surgical resection, or biopsy for patients who do not undergo resection, followed by standard of care (SOC) adjuvant chemoradiation per National Comprehensive Cancer Network (NCCN) guidelines.
Interventions
1-3 fractions given over 1 week as assigned in phase I and as determined to be the maximum tolerated dose (MTD) in phase II
200 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.
750mg intravenously (IV) on Days 1, 8, 15, and 22.
Eligibility Criteria
You may qualify if:
- 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.
- Clinical stage III, IVA, or IVB disease as defined using the 8th (2017) edition of the tumor, node, metastasis (TNM) staging system by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC):
- T1-2, N1-3 or
- T3, any N or
- T4, any N
- Documented tumor PD-L1 CPS ≥ 1 (by PD-L1 IHC pharmDx assay), determined locally.
- Willing to provide blood and newly obtained core or excisional biopsy of tumor lesion pre-treatment and at the time of surgery for pathologic and correlative analyses.
- Age 18 years or older at the time of informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ and marrow function as defined below:
- Absolute neutrophil count ≥ 1.5 K/cumm
- Platelets ≥ 100 K/cumm
- Hemoglobin ≥ 9 g/dL (without PRBC transfusion in the prior 7 days)
- Total serum bilirubin ≤ 1.5 x IULN (except for subjects with documented diagnosis of Gilbert syndrome). For subjects with a documented diagnosis of Gilbert's syndrome, total bilirubin must be ≤ 3.0 × ULN, provided that direct bilirubin is within normal limits
- +5 more criteria
You may not qualify if:
- 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.
- Active autoimmune disease requiring systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Active systemic infection requiring either hospitalization or parenteral anti-infective therapy within 2 weeks before first dose of study treatment.
- Chronic hepatitis B virus (HBV) infection with active disease meeting the criteria for anti-HBV therapy but not on a suppressive antiviral therapy prior to initiation of study treatment. HBV testing not required in the absence of known history of infection. Note: Subjects who are hepatitis B surface antigen positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. These subjects should remain on antiviral therapy throughout the study treatment period and follow local guidelines for HBV antiviral therapy post completion of study treatment.
- Known history of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible provided they completed curative antiviral therapy at least 4 weeks prior to initiation of study treatment. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.
- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) with viral load \>0 or CD4\<350. HIV testing is not required in the absence of known history of infection.
- Receipt of any organ transplantation, including autologous and allogeneic stem cell transplantation, except for transplants that do not require immunosuppression.
- Known to be diagnosed and/or treated for any other additional malignancy within 2 years prior to randomization with the exception of the following: curatively treated basal cell carcinoma or squamous cell carcinoma of the skin, and curatively resected in situ cervical cancer, and curatively resected in situ breast cancer, and low-risk early stage prostate cancer defined as follows: Stage T1c or T2a with a Gleason score ≤ 6 and prostatic-specific antigen \< 10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study entry. Other exceptions may be considered with the PI's consultation. The time requirement for no malignancy for 2 years does not apply to the cancer for which a subject is enrolled in the study.
- Any condition requiring systemic treatment with either corticosteroids (\>10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 7 days prior to the first dose of study treatment, except for topical, intranasal, intrabronchial, or ocular steroids. Corticosteroid use as premedication for allergic reactions (e.g., intravenous contrast), or as a prophylactic management of AEs related to the therapies specified in the protocol is allowed. The use of physiologic doses of corticosteroids may be approved after consultation with the principle-Investigator.
- Use of a live or live attenuated vaccine within 4 weeks prior to Screening. Note: Administration of killed, recombinant, or inactivated vaccines is allowed.
- Pregnant or breastfeeding. People of childbearing potential must have a negative pregnancy test at screening and within 7 days of first dose of study treatment.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Washington University School of Medicinelead
- Bicara Therapeuticscollaborator
Study Sites (1)
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sana Karam, MD, PhD
Washington University School of Medicine
- PRINCIPAL INVESTIGATOR
Sidharth Puram, MD, PhD
Washington University School of Medicine
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 20, 2026
First Posted
April 27, 2026
Study Start (Estimated)
June 30, 2026
Primary Completion (Estimated)
August 31, 2028
Study Completion (Estimated)
August 31, 2033
Last Updated
April 27, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share