Clinical trial NCT06788990: FORTIFI-HN01: A Study of Ficerafusp Alfa (BCA101) or Placebo in Combination With Pembrolizumab in First-Line PD-L1-pos, R or M HNSCC
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Metastatic Head and Neck Squamous Cell Carcinoma
Recurrent Head and Neck Squamous Cell Carcinoma
Keywords: Phase 2/3
Ficerafusp alfa
BCA101
Recurrent Head and Neck Squamous Cell Carcinoma (R HNSCC)
Metastatic Head and Neck Squamous Cell Carcinoma (M HNSCC)
Pembrolizumab
EGFR
TGF-beta
Lead sponsor: Bicara Therapeutics
Sponsor class: INDUSTRY
First posted: 2025-01-23
Enrollment: 650
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

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.

Eligibility criteria: 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 (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 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.

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

Primary outcomes:
measure: Phase 2 - Incidence and severity of TEAEs, treatment-treatment emergent SAEs TEAEs leading to dose interruption, dose reduction, or permanent discontinuation.
timeFrame: Up to 30 days post end of treatment for TEAEs (90 days for SAEs).
measure: Phase 2 - Objective Response Rate (ORR) per RECIST 1.1 by blinded independent central review (BICR)
timeFrame: Approximately 1 year.
measure: Phase 3 - Objective Response Rate (ORR) per RECIST 1.1 by BICR.
timeFrame: Approximately 2 years.
measure: Phase 3 - Overall Survival (OS)
timeFrame: Approximately 3 years.
Secondary outcomes:
measure: Phase 2 - Duration of Response (DOR) per RECIST 1.1 by BICR.
timeFrame: Approximately 1 year.
measure: Phase 3 - Incidence and severity of TEAEs, treatment-treatment emergent SAEs TEAEs leading to dose interruption, dose reduction, or permanent discontinuation.
timeFrame: Up to 30 days post end of treatment for TEAEs (90 days for SAEs).
measure: Phase 3 - Progression-free survival (PFS) per RECIST 1.1 by BICR.
timeFrame: Approximately 3 years.
measure: Phase 3 - Objective Response Rate (ORR) per RECIST 1.1 by BICR.
timeFrame: Approximately 3 years.
measure: Phase 3 - Duration of Response (DOR) per RECIST 1.1 by BICR.
timeFrame: Approximately 3 years.
measure: Phase 3 - Clinical Benefit Rate (CBR) per RECIST 1.1 by BICR.
timeFrame: Approximately 3 years.
measure: Phase 3 - ORR, per RECIST 1.1 by investigator's assessment.
timeFrame: Approximately 3 years.
measure: Phase 3 - DOR, per RECIST 1.1 by investigator's assessment.
timeFrame: Approximately 3 years.
measure: Phase 3 - PFS, per RECIST 1.1 by investigator's assessment.
timeFrame: Approximately 3 years.
measure: Phase 3 - 14. Time to deterioration (TTD) in global health status measured by the EORTC QLQ C30 items for global health status and quality of life scale (item 29/30)
timeFrame: Approximately 3 years.
measure: Phase 3 - Time to deterioration (TTD) in pain measured by the EORTC HN 35 (items 31-34) pain domain.
timeFrame: Approximately 3 years.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Site #0107
state: California
city: Los Angeles
country: United States
facility: Site #0106
state: California
city: Aurora
country: United States
facility: Site #0122
state: Colorado
city: Aurora
country: United States
facility: Site#0121
state: Colorado
city: Newark
country: United States
facility: Site#0127
state: Delaware
city: Palm Bay
country: United States
facility: Site #0136
state: Florida
city: Iowa City
country: United States
facility: Site#0140
state: Iowa
city: Lexington
country: United States
facility: Site#0109
state: Kentucky
city: Louisville
country: United States
facility: Site#0111
state: Kentucky
city: Louisville
country: United States
facility: Site#0115
state: Kentucky
city: Boston
country: United States
facility: Site #0131
state: Massachusetts
city: Boston
country: United States
facility: Site#0101
state: Massachusetts
city: Hackensack
country: United States
facility: Site #0119
state: New Jersey
city: Durham
country: United States
facility: Site#0118
state: North Carolina
city: Cincinnati
country: United States
facility: Site#0117
state: Ohio
city: Portland
country: United States
facility: Site #0113
state: Oregon
city: Pittsburgh
country: United States
facility: Site #0103
state: Pennsylvania
city: Charleston
country: United States
facility: Site#0104
state: South Carolina
city: Nashville
country: United States
facility: Site#0126
state: Tennessee
city: Houston
country: United States
facility: Site#0102
state: Texas
city: Charlottesville
country: United States
facility: Site#0134
state: Virginia
city: Vancouver
country: United States
facility: Site#0120
state: Washington
city: Waratah
country: Australia
facility: Site#0304
state: New South Wales
city: Tugun
country: Australia
facility: Site#0307
state: Queensland
city: North Melbourne
country: Australia
facility: Site#0301
state: Victoria
Study officials:
References: