Recruiting 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

Phase II / Phase III Interventional Metastatic Head and Neck Squamous Cell Carcinoma Recurrent Head and Neck Squamous Cell Carcinoma

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Ficerafusp alfa, Pembrolizumab (KEYTRUDA®), Placebo.
Who it may be relevant to: Registry conditions: Metastatic Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Austria, Belgium +21
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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

Overview

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.

Interventions

Drug Ficerafusp alfa
Investigational
Drug Pembrolizumab (KEYTRUDA®)
Immunotherapy agent used in combination with investigational agent
Drug Placebo
Placebo Control

Primary outcome measures

Phase 2 - Incidence and severity of TEAEs, treatment-treatment emergent SAEs TEAEs leading to dose interruption, dose reduction, or permanent discontinuation. [Time frame: Up to 30 days post end of treatment for TEAEs (90 days for SAEs).]
Phase 2 - Objective Response Rate (ORR) per RECIST 1.1 by blinded independent central review (BICR) [Time frame: Approximately 1 year.]
Phase 3 - Objective Response Rate (ORR) per RECIST 1.1 by BICR. [Time frame: Approximately 2 years.]
Phase 3 - Overall Survival (OS) [Time frame: Approximately 3 years.]

Secondary outcome measures (11)

Phase 2 - Duration of Response (DOR) per RECIST 1.1 by BICR. [Time frame: Approximately 1 year.]
Phase 3 - Incidence and severity of TEAEs, treatment-treatment emergent SAEs TEAEs leading to dose interruption, dose reduction, or permanent discontinuation. [Time frame: Up to 30 days post end of treatment for TEAEs (90 days for SAEs).]
Phase 3 - Progression-free survival (PFS) per RECIST 1.1 by BICR. [Time frame: Approximately 3 years.]
Phase 3 - Objective Response Rate (ORR) per RECIST 1.1 by BICR. [Time frame: Approximately 3 years.]
Phase 3 - Duration of Response (DOR) per RECIST 1.1 by BICR. [Time frame: Approximately 3 years.]
Phase 3 - Clinical Benefit Rate (CBR) per RECIST 1.1 by BICR. [Time frame: Approximately 3 years.]
Phase 3 - ORR, per RECIST 1.1 by investigator's assessment. [Time frame: Approximately 3 years.]
Phase 3 - DOR, per RECIST 1.1 by investigator's assessment. [Time frame: Approximately 3 years.]
Phase 3 - PFS, per RECIST 1.1 by investigator's assessment. [Time frame: Approximately 3 years.]
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) [Time frame: Approximately 3 years.]
Phase 3 - Time to deterioration (TTD) in pain measured by the EORTC HN 35 (items 31-34) pain domain. [Time frame: Approximately 3 years.]

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.
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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Double blind
Primary purpose: Treatment