FORTIFI-HN01: A Study of Ficerafusp Alfa (BCA101) or Placebo in Combination With Pembrolizumab in First-Line PD-L1-pos, R or M HNSCC

Inclusion Criteria:

• Age ≥18 years on the day the Informed Consent Form is signed.

• Histologically or cytologically confirmed R or M HNSCC. Eligible primary tumorlocations are oral cavity, hypopharynx, larynx or oropharynx (with documentedHPV-negative disease if presenting with OPSCC). Note: primary tumor location ofparanasal sinuses and nasopharynx, any histology are excluded.

• No prior systemic therapy administered in the R or M setting; and completed systemictherapy >6 months prior if given as part of multimodal treatment for locoregionallyadvanced disease in the adjuvant or definitive setting.

• Archival tumor tissue or willing to undergo pretreatment biopsy at Screening ifarchival tissue is insufficient or unavailable.

• PD-L1 CPS ≥1 (by PD-L1 IHC 22C3 pharmDx assay).

• Measurable disease based on RECIST 1.1.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Adequate organ function, as defined in the protocol.

Exclusion Criteria:

• Disease suitable for local therapy administered with curative intent.

• Prior treatment with anti-TGFβ therapy.

• Prior therapy with an anti-EGFR antibody (exception: radio sensitizing agents andmultimodal treatment for locoregionally advanced disease).

• Prior history of Grade ≥2 intolerance or hypersensitivity reaction to anti-EGFRtherapy or other murine proteins.

• Prior therapy with an immune checkpoint inhibitor completed within 6 months prior tostudy treatment initiation.

• Progressive disease <6 months from completion of curative intent systemic therapyfor locoregionally advanced HNSCC.

• Life expectancy less than 3 months.

• Known active central nervous system metastases, history of spinal cord compressionfrom tumor involvement, a history of carcinomatous meningitis, or leptomeningealdisease are excluded.

• Current active major bleeding, or a recent major bleeding episode within 4 weeksprior to enrollment.

• Subject participated in another clinical study or received treatment with anotherinvestigational drug must wait at least 5 half-lives of the treatment received or 4weeks (whichever is shorter) following prior therapy.

• Active autoimmune disease requiring systemic treatment in the past 2 years.

• Subjects with chronic hepatitis B virus (HBV) infection with active disease who meetthe criteria for anti-HBV therapy and are not on a suppressive antiviral therapyprior to initiation of study treatment.

• Subjects with a known history of hepatitis C virus (HCV) who have not completedcurative antiviral treatment or have an HCV viral load above the limit ofquantification at Screening.

• Known history of human immunodeficiency virus (HIV).

• Receipt of any organ transplantation, including autologous and allogeneic stem celltransplantation, with the exception of transplants that do not requireimmunosuppression.

• Known to be diagnosed and/or treated for any other additional malignancy within 2years prior to randomization with the exception of the following: curatively treatedbasal cell carcinoma or squamous cell carcinoma of the skin, and curatively resectedin situ cervical cancer, and curatively resected in situ breast cancer, and low-riskearly stage prostate cancer.

• Any condition requiring systemic treatment with either corticosteroids (>10 mg dailyof prednisone or equivalent) or other immunosuppressive medication within 7 daysprior to the first dose of study treatment, except for topical, intranasal,intrabronchial, or ocular steroids.

• Use of a live or live attenuated vaccine within 4 weeks prior to Screening.

Other Inclusion/Exclusion criteria may apply as defined in the protocol.