A Study Evaluating Ficerafusp Alfa (BCA101) QW in Combination With Pembrolizumab vs Alternative Ficerafusp Alfa Dosing in 1L R or M HNSCC

The mechanism of action of ficerafusp alfa involves dual targeting of two cancer targets, EGFR and TGF-β, which are known to drive solid tumor growth and metastasis.

All participants will receive ficerafusp alfa 1500 mg once weekly (QW in combination with pembrolizumab 200 mg every three weeks (Q3W) for 12 weeks (loading phase). Participants who remain on study without progression at the end of the loading phase will enter the maintenance phase and will be randomized 2:1 to one of the following arms:

Arm A: Ficerafusp alfa 2250 mg Q3W [alternative dose] + pembrolizumab 200 mg Q3W Arm B: Ficerafusp alfa 1500 mg QW [standard dose] + pembrolizumab 200 mg Q3W.

Inclusion criteria

• Age ≥18 years on the day the Informed Consent Form is signed.
• Histologically or cytologically confirmed R or M HNSCC. Eligible primary tumor locations are oral cavity, hypopharynx, larynx or oropharynx (with documented HPV-negative disease if presenting with OPSCC). Note: primary tumor location of paranasal sinuses and nasopharynx, any histology are excluded.
• No prior systemic therapy administered in the R or M setting; and completed systemic therapy >6 months prior if given as part of multimodal treatment for locoregionally advanced disease in the adjuvant or definitive setting.
• Archival tumor tissue or willing to undergo pretreatment biopsy at Screening if archival tissue is insufficient or unavailable.
• PD-L1 CPS ≥1.
• 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 and multimodal treatment for locoregionally advanced disease).
• Prior history of Grade ≥2 intolerance or hypersensitivity reaction to anti-EGFR therapy or other murine proteins.
• Prior therapy with an immune checkpoint inhibitor completed within 6 months prior to study treatment initiation.
• Progressive disease <6 months from completion of curative intent systemic therapy for locoregionally advanced HNSCC.
• Life expectancy less than 3 months.
• Known active central nervous system metastases, history of spinal cord compression from tumor involvement, a history of carcinomatous meningitis, or leptomeningeal disease are excluded.
• Current active major bleeding, or a recent major bleeding episode within 4 weeks prior to enrollment.
• Subject participated in another clinical study or received treatment with another investigational drug must wait at least 5 half-lives of the treatment received or 4 weeks (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 meet the criteria for anti-HBV therapy and are not on a suppressive antiviral therapy prior to initiation 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.
• Known history of human immunodeficiency virus (HIV).
• Receipt of any organ transplantation, including autologous and allogeneic stem cell transplantation, with the exception of 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.
• 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.
• Use of a live or live attenuated vaccine within 4 weeks prior to Screening.