Title
A Multicenter, Randomized, Double-blind, Phase 2/3 Study of Ficerafusp Alfa (BCA101) or Placebo in Combination with Pembrolizumab for First-Line Treatment of PD-L1-positive, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Description
A Multicenter, Randomized, Double-blind, Phase 2/3 Study of Ficerafusp Alfa (BCA101) or Placebo in Combination With Pembrolizumab for First-Line Treatment of PD-L1-positive, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

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

Phase 2 of the study will identify an optimal biologic dose (OBD) supported by the safety, tolerability, PK, PD, and efficacy data of ficerafusp alfa. In this part, eligible subjects will be randomized to one of three treatment arms at a 1:1:1 ratio:

-Arm A: ficerafusp alfa 1500 mg once weekly (QW) + pembrolizumab 200 mg every three weeks (Q3W).
-Arm B: ficerafusp alfa 750 mg QW + pembrolizumab 200 mg Q3W.
-Arm C (control): placebo QW + pembrolizumab 200 mg Q3W.

The primary objective for the phase 3 portion is to compare the efficacy in subjects treated with ficerafusp alfa at the selected OBD in combination with pembrolizumab versus placebo with pembrolizumab. Eligible subjects will be randomized 2:1 in the treatment versus control arm during the phase 3 portion.

Treatment Ficerafusp alfa is directed against two targets, Epidermal Growth Factor Receptor (EGFR) and Transforming Growth Factor beta (TGF-β).

This study intends to evaluate the safety and efficacy of ficerafusp alfa in combination with pembrolizumab versus placebo with pembrolizumab in 1L PD-L1-positive, recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC).

Key Eligibility 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.

Applicable Disease Sites
Head and Neck

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital; Wm. S. Middleton Memorial VA Hospital