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

Official 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).

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 650 participants

Study Arms

• Phase 2 Arm A (EXPERIMENTAL)
  ficerafusp alfa 1500 mg QW + pembrolizumab 200 mg every 3 weeks (Q3W)
• Phase 2 Arm B (EXPERIMENTAL)
  ficerafusp alfa 750 mg QW + pembrolizumab 200 mg Q3W
• Phase 2 Arm C (PLACEBO_COMPARATOR)
  placebo QW + pembrolizumab 200 mg Q3W
• Phase 3 OBD Arm (EXPERIMENTAL)
  ficerafusp alfa OBD + pembrolizumab 200 mg Q3W
• Phase 3 Arm C (PLACEBO_COMPARATOR)
  placebo QW + pembrolizumab 200 mg Q3W

Interventions

• DRUG: Ficerafusp alfa — Investigational
• DRUG: Pembrolizumab (KEYTRUDA®) — Immunotherapy agent used in combination with investigational agent
• DRUG: Placebo — Placebo Control

Primary Outcomes

• Phase 2 - Incidence and severity of TEAEs, treatment-treatment emergent SAEs TEAEs leading to dose interruption, dose reduction, or permanent discontinuation. (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) (Approximately 1 year.)
• Phase 3 - Objective Response Rate (ORR) per RECIST 1.1 by BICR. (Approximately 2 years.)
• Phase 3 - Overall Survival (OS) (Approximately 3 years.)

Secondary Outcomes

• Phase 2 - Duration of Response (DOR) per RECIST 1.1 by BICR. (Approximately 1 year.)
• Phase 3 - Incidence and severity of TEAEs, treatment-treatment emergent SAEs TEAEs leading to dose interruption, dose reduction, or permanent discontinuation. (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. (Approximately 3 years.)
• Phase 3 - Objective Response Rate (ORR) per RECIST 1.1 by BICR. (Approximately 3 years.)
• Phase 3 - Duration of Response (DOR) per RECIST 1.1 by BICR. (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.

Trial Locations

• Site # 0137, Birmingham, Alabama, United States
• Site #0147, Phoenix, Arizona, United States
• Site #0107, La Jolla, California, United States
• Site #0106, Los Angeles, California, United States
• Site#0144, Sacramento, California, United States
• Site #0130, San Francisco, California, United States
• Site #0150, Stanford, California, United States
• Site #0122, Aurora, Colorado, United States
• Site #0124, Aurora, Colorado, United States
• Site#0121, Aurora, Colorado, United States
• ...and 10 more locations

Contact Information

• Medical Affairs — CONTACT
  Phone: 1-617-468-4219
  Email: FORTIFI_inquiries@bicara.com

More Metastatic Head and Neck Squamous Cell Carcinoma Trials

View all Metastatic Head and Neck Squamous Cell Carcinoma clinical trials