Neoadjuvant Ficerafusp Alfa With Pembrolizumab in Resectable SCC

NCT07465276 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-829
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

This trial is to evaluate the safety and efficacy of ficerafusp alfa in combination with pembrolizumab prior to surgical resection in participants with resectable, high-risk, locoregionally advanced, PD-L1-positive squamous cell carcinoma of the head and neck (HNSCC). The names of the study drugs used in this research study are:

• ficerafusp alfa (a type of bifunctional antibody and recombinant fusion protein)
• pembrolizumab (a type of monoclonal antibody)

Conditions

Head and Neck Squamous Cell Carcinoma (HNSCC); Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• Pathologic Treatment Response-2 (pTR-2) Rate

  pTR-2 rate is defined as ≥50% pathological response of the primary tumor using the surgical specimen following neoadjuvant therapy as established by 2 independent pathologists.

  Assessed at time of surgical resection, between days 30 and 42 from start of neoadjuvant treatment.

Secondary Outcomes (5)

• Median Event-free survival (EFS)

  Disease assessed every 3 months up to 24 months from date of surgery (+42 days from start of neoadjuvant therapy).

• Median Overall Survival

  Survival assessed every 3 months up to 24 months from date of surgery (+42 days from start of neoadjuvant therapy).

• Pathologic Response Rate by PD-LI Combined positive score (CPS) Subgroup

  Assessed at time of surgical resection, between days 30 and 42 from start of neoadjuvant treatment.

• Major Pathologic Response Rate

  Assessed at time of surgical resection, between days 30 and 42 from start of neoadjuvant treatment.

• Pre-Operative Objective Response Rate (ORR)

  Assessed over 2 cycles of neoadjuvant treatment (cycle duration=21 days), up to day 42.

Study Arms (1)

Ficerafusp Alfa plus Pembrolizumab

EXPERIMENTAL

32 participants will be enrolled and will complete: * Baseline visit * Cycle 1 (21 day cycle): * Day 1: predetermined dose of Prembrolizumab 1x daily. * Days 1, 8, and 15: predetermined dose of Ficerafusp Alfa 1x daily. * Cycle 2 (21 day cycle): * Day 1: predetermined dose of Prembrolizumab 1x daily. * Day 1: predetermined dose of Ficerafusp Alfa 1x daily. * Standard of care surgery * End of treatment visit * Follow up for up to 2 years

Drug: Ficerafusp alfa; Drug: Pembrolizumab

Interventions

Ficerafusp alfa DRUG

Bifunctional antibody and recombinant fusion protein, single-use vial, via intravenous (into the vein) infusion per protocol.

Also known as: FmAb2, BCA101

Ficerafusp Alfa plus Pembrolizumab

Pembrolizumab DRUG

Monoclonal antibody, single-dose vial, via intravenous infusion per protocol.

Also known as: Keytruda

Ficerafusp Alfa plus Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed, untreated and newly diagnosed, locoregionally advanced head and neck squamous cell carcinoma (HNSCC) arising from oral cavity, oropharynx (with documented HPV-negative disease if presenting with oropharyngeal SCC), larynx, or hypopharynx.
• Participants should have resectable disease at baseline per the discretion of the treating surgical oncologist.
• Participants must have clinical stage disease as defined below 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: III
• T3, any N: III, IVA, IVB
• T4, any N: IVA, IVB
• Tumor must be PD-L1 positive with a CPS score equal to 1 or greater (by any approved assay or scoring method).
• Participants must be willing to provide blood and tissue pre-treatment and at the time of surgery for pathologic and correlative analyses. Specifically, willingness to provide a newly obtained core or excisional biopsy of a tumor lesion from the primary tumor site.
• Age 18 years or older at the time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Participants must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥1500/mcL
• platelets ≥100 x 109/L
• total serum bilirubin ≤1.5X upper limit of normal (ULN) (except for subjects with documented Gilbert syndrome) and AST (SGOT) and ALT (SGPT) ≤2.5X ULN
• AST(SGOT) / ALT (SGPT) ≤3X ULN

You may not qualify if:

• Recurrent or metastatic (M1 or IVC disease by AJCC 2017 8th edition staging) HNSCC or very early-stage HNSCC (stage I or II by AJCC 2017 8th edition staging); or head and neck cancer arising at other primary subsites such as the skin, paranasal sinuses, nasal cavity, or salivary glands.
• HPV-associated oropharyngeal cancer (as determined by p16 positivity by immunohistochemistry and/or confirmatory HPV RNA ISH or PCR testing, or by plasma HPV DNA testing results).
• Inoperable or surgically unresectable at baseline per the treating investigator(s).
• ECOG performance status of 2 or greater.
• Prior exposure to anti-EGFR antibody or anti-PD-1 immunotherapy.
• Significant bleeding risk peri-operatively at the judgment of the treating investigator(s); such as those with a known bleeding diathesis or experiencing a major bleeding episode within 4 weeks of enrolling to the study.
• 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.
• Known psychiatric, behavioral, or substance abuse disorders that would interfere with cooperation of the study requirements.
• Subjects with chronic hepatitis B virus (HBV) infection with active disease who meet the criteria for anti-HBV therapy and are not on a suppressive antiviral therapy prior to initiation of study treatment. 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. Note: Subjects should remain on antiviral therapy throughout the study treatment period and follow local guidelines for HBV antiviral therapy post completion of study treatment.
• Subjects with a known history of hepatitis C virus (HCV) who have not completed curative antiviral treatment or have an HCV viral load above the limit of quantification at Screening. Note: subjects must have completed curative antiviral therapy at least 4 weeks prior to treatment.
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). HIV testing is not required unless mandated by local health authority.
• 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 registration 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. Other exceptions may be considered with the input of the Sponsor-Investigator.
• 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 Sponsor-Investigator.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bicara Therapeutics: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Glenn Hanna

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Glenn Hanna

CONTACT

617-632-3779; Gjhanna@partners.org

Glenn Hanna

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 6, 2026
• First Posted: March 11, 2026
• Study Start: March 26, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2030
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer office for Dana -Farber Innovations (BODFI) at innovations@dfci.harvard.edu

Locations

US (2)