A Study to See if Giving Fianlimab and Cemiplimab Together is Better Than Cemiplimab Alone at Treating Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Official title

Phase II Randomized Study of Fianlimab Plus Cemiplimab Versus Cemiplimab Plus Placebo in First-Line Treatment of Participants With Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) That Is Positive for PD-L1 Expression

Overview

This study is researching an experimental drug called fianlimab (also called REGN3767), combined with a medication called cemiplimab compared against cemiplimab combined with placebo (a placebo looks like a treatment but does not contain any real medicine), collectively called "study drugs" in this form. The study is focused on participants with head and neck cancers who have not been previously treated for head and neck cancer that has come back or spread to other parts of the body, referred to as recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The study is looking at several other research questions, including: * What side effects may happen from taking the study drugs * How much of each study drug is in the blood at different times * Whether the body makes antibodies against the study drug(s) individually (which could make the study drugs less effective or could lead to side effects) * Compatible research to better understand the study drugs and HNSCC

Interventions

• Drug FDC fianlimab+cemiplimab
  Fixed-Dose Combination (FDC) Administered per the protocol
• Drug Cemiplimab
  Administered per the protocol
• Drug Placebo
  Administered per the protocol

Primary outcome measures

• Overall Response Rate (ORR) [Time frame: Up to 90 days after last study treatment, approximately 58 months]

Secondary outcome measures (12)

• Incidence of Adverse Events (AEs) [Time frame: Up to 90 days after last study treatment, approximately 58 months]
• Severity of AEs [Time frame: Up to 90 days after last study treatment, approximately 58 months]
• Incidence of Treatment Emergent Adverse Events (TEAEs) [Time frame: Up to 90 days after last study treatment, approximately 58 months]
• Incidence of immune-mediated Adverse Events (imAEs) [Time frame: Up to 90 days after last study treatment, approximately 58 months]
• Incidence of treatment-related AEs [Time frame: Up to 90 days after last study treatment, approximately 58 months]
• Incidence of Adverse Events of Special Interest (AESIs) [Time frame: Up to 90 days after last study treatment, approximately 58 months]
• Incidence of Serious Adverse Events (SAEs) [Time frame: Up to 90 days after last study treatment, approximately 58 months]
• Incidence of AEs leading to discontinuation [Time frame: Up to 90 days after last study treatment, approximately 58 months]
• Incidence of AEs leading to death [Time frame: Up to 90 days after last study treatment, approximately 58 months]
• Incidence of laboratory abnormalities [Time frame: Up to 90 days after last study treatment, approximately 58 months]
• Disease Control Rate (DCR) per investigator assessment [Time frame: Up to 90 days after last study treatment, approximately 58 months]
• Duration of Response (DOR) per investigator assessment or death, whichever occurs first [Time frame: Up to 90 days after last study treatment, approximately 58 months]

Eligibility criteria

Inclusion criteria

• Have histologically confirmed (by local pathology) R/M HNSCC that is considered incurable by local therapies
• Primary tumor location of oral cavity, oropharynx, larynx, or hypopharynx (patients with cervical neck node SCC with occult primary as described in the protocol
• PD-L1 expression Combined Positive Score (CPS) ≥1 documented with a previously PD-L1 obtained Immunohistochemistry (IHC) result prior to screening, as described in protocol
• Oropharynx cancer participants only: HPV status, based on a previously documented result prior to screening, must have been established in a surgical biopsy specimen or a core biopsy specimen as described in the protocol
• At least 1 lesion that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as described in the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ and bone marrow function as described in the protocol

Exclusion criteria

Medical Conditions

• Participants who have Progressive Disease (PD) within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC as described in the protocol
• Participants who have a primary tumor site of nasopharynx, paranasal sinus or salivary gland (any histology)
• Head and neck SCC with unknown primary site as described in the protocol
• Participants with active, known, or suspected autoimmune disease that has required systemic therapy within 5 years of the projected enrollment date as described in the protocol
• History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management
• History or current evidence of significant cardiovascular disease including, myocarditis, congestive heart failure (as defined by New York Heart Association Functional Classification III and IV), unstable angina, serious uncontrolled arrhythmia, and myocardial infarction 6 months prior to study enrollment.

Prior/Concomitant Therapy

• Participants who have received prior systemic anticancer therapy in the R/M HNSCC setting as described in the protocol
• Participants with a condition requiring corticosteroid therapy (>10 mg prednisone/prednisolone/day or equivalent) within 14 days of the first dose of study drug as described in the protocol

Note: Other protocol defined Inclusion/ Exclusion Criteria apply

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

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 17 centers

• University of California Los Angeles — Los Angeles
• Samuel Oschin Cancer Center — Los Angeles
• Orlando Health — Orlando
• Emory University School of Medicine — Atlanta
• Northwestern University — Evanston
• St. Elizabeth Healthcare — Edgewood
• Norton Cancer Institute — Louisville
• Henry Ford Cancer Institute/Henry Ford Health System — Detroit
• … and 9 more centers

Spain · 7 centers

• Hospital Universitario Virgen del Rocio — Seville
• Hospital Clinic — Barcelona
• Complejo Hospitalario Universitario de a Coruna — A Coruña
• Hospital Universitario de Navarra — Pamplona
• Centro Oncologico de Galicia — A Coruña
• Hospital Universitario La Paz — Madrid
• Hospital Universitario Miguel Servet — Zaragoza

Australia · 4 centers

• Wide Bay Hospital and Health Service - Cancer Care Services - Bundaberg — Bundaberg
• Cairns Hospital — Cairns
• Wide Bay Hospital and Health Service — Hervey Bay
• Peter MacCallum Cancer Centre (PMCC) — Melbourne

France · 3 centers

• Centre Jean Perrin — Clermont-Ferrand
• Timone Hospital - AP-HM — Marseille
• Hopital Europeen Geroges Pompidou AP-HP — Paris

Italy · 1 center

• Istituto Europeo di Oncologia — Milan

Identifiers

NCT: NCT06769698 · R3767-ONC-2431 · 2024-517620-19-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗